Having a yearly mammogram greatly reduces the risk of mastectomy following breast cancer in women between the ages of 40 and 50, according to a study being presented today at the annual meeting of the Radiological Society of North America (November 28 - December 3, 2010, McCormick Place, Chicago).
"The results of this study support the importance of regular screening in the 40 to 50 age group," said lead author Nicholas M. Perry, M.B.B.S., F.R.C.S., F.R.C.R., director of The London Breast Institute at The Princess Grace Hospital in London. "Women in this age group who had undergone mammography the previous year had a mastectomy rate of less than half that of the others."
An estimated 207,090 new cases of invasive breast cancer will be diagnosed in American women in 2010. Currently, the American Cancer Society recommends annual mammography screening for women beginning at age 40 in the U.S., but last year, the U.S. Preventive Services Task Force recommended changing the guidelines to begin screening biennially (every other year) at age 50. There are no routine screening guidelines for women under 50 in the U.K.
The researchers studied the benefits of screening women between the ages of 40 and 50, the frequency of mammography and the type of treatment after breast cancer diagnosis.
Dr. Perry and colleagues reviewed the clinical data available on women from 40 to 50 that had been diagnosed with breast cancer and treated at The London Breast Institute. Between 2003 and 2009, 971 women had been diagnosed with breast cancer. At the time of diagnosis, 393 (40%) of the women were under 50, with 156 of these women completing treatment at the center. Of the treated women, 114 (73%) had no prior mammograms. Forty-two women had been previously screened with mammography, of whom 29 had at least one mammogram within the previous two years. Of those, 16 women had a mammogram one year prior.
"We reviewed the records of the women needing mastectomy to determine whether or not they had undergone mammography the previous year," Dr. Perry said. "We were surprised at the degree of benefit obtained from yearly screening in this age group."
Data showed that mastectomy was the required treatment for 3 (19%) of the 16 women who had been screened the prior year, compared to 64 (46%) of the 140 women who had not been screened in the past year.
"Regular screening is already proven to lower the chance of women dying from breast cancer," Dr. Perry said. "The results of our study support the importance of regular screening in the under-50 age group and confirm that annual mammography improves the chances of breast conservation should breast cancer develop."
Dr. Perry's coauthors for this article are Sue Milner, B.Sc., D.C.R., Kefah Mokbel, M.B.B.S., M.S., F.R.C.S., Stephen W. Duffy, B.Sc., M.Sc., and Katja Pinker, M.D.
For more information
Prior Mammography in Women Aged 40-50 at a UK Center in Accordance with ACS Guidelines Lowers Mastectomy Rate Following Breast Cancer (Abstract)
This article was first published online at Onco'Zine - The International Cancer Network
Showing posts with label Cancer. Show all posts
Showing posts with label Cancer. Show all posts
Wednesday, December 1, 2010
Thursday, November 25, 2010
Personalized Cancer Therapy Requires New Strategies for Cancer Drug Development
Millions of cancer patients worldwide may soon be able to receive more effective, personalized treatments for their disease thanks to developments in the understanding of cancer biology, experts will say at the Cancer Biology for Clinicians Symposium organized by the European Society for Medical Oncology (ESMO) in Nice, France on 26-27 November.
To make the most of this coming transformation, governments, pharmaceutical companies and doctors urgently need to adapt the way drugs are developed, the experts say.
"Cancer therapy is arguably at the most exciting time in its history," said José Baselga, from MGH Cancer Center in Boston, USA, co-chair of the symposium and ESMO Past-President. "It is at the confluence of two new movements, one toward personalized medicine and the other toward the use of new molecularly targeted cancer therapeutics that exploit the tumor's genetic and molecular signature. These movements provide many challenges, but also the opportunity for making paradigm shifts in the way we think of and treat cancer."
Personalized treatment has become increasingly available for cancers over the past decade. This has partly come about as scientists have found that common tumors such as breast cancer are in fact a mixture of several disease types with distinct molecular features. Meanwhile, molecular targeted drugs have also been developed that inhibit particular molecular targets involved in some cancers.
"As our understanding of cancer biology develops further, these kinds of personalized treatments are expected to become available for many more cancer types," said Fabrice André, from Institut Gustave Roussy, France, ESMO spokesperson co-chairing a session at the symposium. "If we want to facilitate the implementation of this kind of personalized medicine, then we urgently need to develop new strategies for cancer drug development."
In particular, it is time to rethink whether the standard model of testing drugs in large phase-III trials is an effective way to bring these targeted cancer drugs to patients, Dr André noted.
"Regulatory processes are becoming increasingly restrictive in providing patient access to potentially innovative new drugs, because even the largest cancer trials generally involve only a small portion of the cancer patient population, and because the drug development process is often more than a decade from the first preclinical study," he added.
This is related to the fact that drug approval usually needs large confirmatory trials that are being done in an unselected population. There is a need for smaller trials done with selected patients to be highly sensitive, a concept that requires the development of molecular selection and relative platforms for doing that.
"It’s clear that we urgently need a new paradigm for drug development, including targeted patient selection for clinical trials, shorter duration of clinical trials and improvement of the cost effectiveness of bringing a new drug to the market."
The ESMO Cancer Biology for Clinicians Symposium, a two-day meeting featuring some of the most eminent researchers in the field, is designed to inform oncologists about the ways cancer biology is changing clinical practice.
"What is most exciting today is the active dialogue between clinicians and laboratory scientists who share an interest in applying the new knowledge of cancer biology to the diagnosis, treatment, and prevention of the disease," said meeting co-chair Mario Dicato, from Centre Hospitalier de Luxembourg.
"In the near future, cancer treatment decisions will be based on biology," said the third meeting co-chair Jean-Charles Soria, ESMO spokesperson from Institut Gustave Roussy, France. "It is therefore vital that medical oncologists have the skills and the knowledge to bring these advances to their patients. The future of oncology will be personalized medicine, and the community needs to discuss how this will be implemented."
The European Society for Medical Oncology (ESMO) is the leading European professional organization committed to advancing the specialty of medical oncology and promoting a multidisciplinary approach to cancer treatment and care. The organization is a powerful alliance of more than 6,000 committed oncology professionals from over 100 countries.
For more information:
Cancer Biology for Clinicians Symposium Program Book
This article was first published online at Onco'Zine - The International Cancer Network
Copyright © 2010 Sunvalley Communication. All rights reserved.
Republication or redistribution of Sunvalley Communication content, including by framing or similar means, is expressly prohibited without the prior written consent of Sunvalley Communication. Sunvalley communication shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Onco'Zine and Oncozine are registered trademarks and trademarks of Sunvalley Communication around the world.
To make the most of this coming transformation, governments, pharmaceutical companies and doctors urgently need to adapt the way drugs are developed, the experts say.
"Cancer therapy is arguably at the most exciting time in its history," said José Baselga, from MGH Cancer Center in Boston, USA, co-chair of the symposium and ESMO Past-President. "It is at the confluence of two new movements, one toward personalized medicine and the other toward the use of new molecularly targeted cancer therapeutics that exploit the tumor's genetic and molecular signature. These movements provide many challenges, but also the opportunity for making paradigm shifts in the way we think of and treat cancer."
Personalized treatment has become increasingly available for cancers over the past decade. This has partly come about as scientists have found that common tumors such as breast cancer are in fact a mixture of several disease types with distinct molecular features. Meanwhile, molecular targeted drugs have also been developed that inhibit particular molecular targets involved in some cancers.
"As our understanding of cancer biology develops further, these kinds of personalized treatments are expected to become available for many more cancer types," said Fabrice André, from Institut Gustave Roussy, France, ESMO spokesperson co-chairing a session at the symposium. "If we want to facilitate the implementation of this kind of personalized medicine, then we urgently need to develop new strategies for cancer drug development."
In particular, it is time to rethink whether the standard model of testing drugs in large phase-III trials is an effective way to bring these targeted cancer drugs to patients, Dr André noted.
"Regulatory processes are becoming increasingly restrictive in providing patient access to potentially innovative new drugs, because even the largest cancer trials generally involve only a small portion of the cancer patient population, and because the drug development process is often more than a decade from the first preclinical study," he added.
This is related to the fact that drug approval usually needs large confirmatory trials that are being done in an unselected population. There is a need for smaller trials done with selected patients to be highly sensitive, a concept that requires the development of molecular selection and relative platforms for doing that.
"It’s clear that we urgently need a new paradigm for drug development, including targeted patient selection for clinical trials, shorter duration of clinical trials and improvement of the cost effectiveness of bringing a new drug to the market."
The ESMO Cancer Biology for Clinicians Symposium, a two-day meeting featuring some of the most eminent researchers in the field, is designed to inform oncologists about the ways cancer biology is changing clinical practice.
"What is most exciting today is the active dialogue between clinicians and laboratory scientists who share an interest in applying the new knowledge of cancer biology to the diagnosis, treatment, and prevention of the disease," said meeting co-chair Mario Dicato, from Centre Hospitalier de Luxembourg.
"In the near future, cancer treatment decisions will be based on biology," said the third meeting co-chair Jean-Charles Soria, ESMO spokesperson from Institut Gustave Roussy, France. "It is therefore vital that medical oncologists have the skills and the knowledge to bring these advances to their patients. The future of oncology will be personalized medicine, and the community needs to discuss how this will be implemented."
The European Society for Medical Oncology (ESMO) is the leading European professional organization committed to advancing the specialty of medical oncology and promoting a multidisciplinary approach to cancer treatment and care. The organization is a powerful alliance of more than 6,000 committed oncology professionals from over 100 countries.
For more information:
Cancer Biology for Clinicians Symposium Program Book
This article was first published online at Onco'Zine - The International Cancer Network
Copyright © 2010 Sunvalley Communication. All rights reserved.
Republication or redistribution of Sunvalley Communication content, including by framing or similar means, is expressly prohibited without the prior written consent of Sunvalley Communication. Sunvalley communication shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Onco'Zine and Oncozine are registered trademarks and trademarks of Sunvalley Communication around the world.
Monday, October 25, 2010
Caution Regarding Use Of Erythropoiesis-Stimulating Agents In Cancer Patients Recommended In New Guideline
An updated joint guideline by the American Society of Hematology (ASH), the world’s largest professional society concerned with the causes and treatment of blood disorders, and the American Society of Clinical Oncology (ASCO) advises physicians about the appropriate use of erythropoiesis-stimulating agents (ESAs), a class of drugs that stimulate the bone marrow to produce more red blood cells, to treat cancer patients with chemotherapy-induced anemia.
While the guideline cautions that ESAs are associated with shorter survival and increased risk of thromboembolism — blood clots — tumor progression and stroke, it also recognizes their major benefit of reducing the need for red blood cell transfusions, which can potentially cause serious infections and adverse reactions in the immune system.
“This updated guideline offers clinicians the latest synthesis of the medical evidence surrounding use of ESAs in patients with cancer, including appropriate cautions where evidence is lacking or where risks may outweigh the use of ESAs,” said J. Douglas Rizzo, MD, MS, Co-Chair of the guideline panel and Professor of Medicine at the Medical College of Wisconsin.
Those risks may include thromboembolism or even death, according to new data cited in the guideline, which suggests that physicians avoid the use of ESAs in cancer patients who are not receiving chemotherapy, except for those with myelodysplastic syndrome (MDS). At the same time, the guideline confirms the effectiveness of ESAs in sparing patients the need for transfusions, which can substantially impact Quality of Life. By recommending that physicians discuss individual risks and benefits of ESAs and blood transfusion with patients prior to therapy, the guideline recognizes the critical role of shared decision-making between the patient and the physician.
In addition to outlining the clotting risks of ESAs, the guideline makes specific recommendations on usage and provides insights into disease progression and patient survival. The guideline also details new thresholds for initiation and modification of ESAs, which are consistent with current US FDA labeling.
Originally published in 2002 and last updated in 2007, the guideline was derived from analysis of individual patient data, various medical literature, and systematic reviews of published clinical trials. In developing the update, panel members considered all relevant literature published between January 2007 and January 2010. Additional evidence was considered when it was considered pertinent to each section of the updated guideline.
“These guidelines touch on almost all aspects of the use of ESAs in patients with cancer and MDS, as well as secondary issues, such as the role of iron supplementation,” said Samuel Silver, MD, a member of ASH’s Committee on Practice and Professor of Internal Medicine at the University of Michigan. “These are issues that confront practicing hematologists and oncologists on a daily basis, and we hope that these evidence-based recommendations will influence practice standards and result in better care for patients.”
For more information:
Rizzo JD, Brouwers M, Hurley P, Seidenfeld J, Arcasoy MO, Spivak JL, Bennett CL, Bohlius J, Evanchuk D, Goode MJ, Jakubowski AA, Regan DH, Somerfield MR. American Society of Clinical Oncology/American Society of Hematology Clinical Practice Guideline Update on the Use of Epoetin and Darbepoetin in Adult Patients With CancerJ Clin Oncol. 2010 Nov 20;28(33):4996-5010. Epub 2010 Oct 25.
This article was first published online at Onco'Zine - The International Cancer Network
While the guideline cautions that ESAs are associated with shorter survival and increased risk of thromboembolism — blood clots — tumor progression and stroke, it also recognizes their major benefit of reducing the need for red blood cell transfusions, which can potentially cause serious infections and adverse reactions in the immune system.
“This updated guideline offers clinicians the latest synthesis of the medical evidence surrounding use of ESAs in patients with cancer, including appropriate cautions where evidence is lacking or where risks may outweigh the use of ESAs,” said J. Douglas Rizzo, MD, MS, Co-Chair of the guideline panel and Professor of Medicine at the Medical College of Wisconsin.
Those risks may include thromboembolism or even death, according to new data cited in the guideline, which suggests that physicians avoid the use of ESAs in cancer patients who are not receiving chemotherapy, except for those with myelodysplastic syndrome (MDS). At the same time, the guideline confirms the effectiveness of ESAs in sparing patients the need for transfusions, which can substantially impact Quality of Life. By recommending that physicians discuss individual risks and benefits of ESAs and blood transfusion with patients prior to therapy, the guideline recognizes the critical role of shared decision-making between the patient and the physician.
In addition to outlining the clotting risks of ESAs, the guideline makes specific recommendations on usage and provides insights into disease progression and patient survival. The guideline also details new thresholds for initiation and modification of ESAs, which are consistent with current US FDA labeling.
Originally published in 2002 and last updated in 2007, the guideline was derived from analysis of individual patient data, various medical literature, and systematic reviews of published clinical trials. In developing the update, panel members considered all relevant literature published between January 2007 and January 2010. Additional evidence was considered when it was considered pertinent to each section of the updated guideline.
“These guidelines touch on almost all aspects of the use of ESAs in patients with cancer and MDS, as well as secondary issues, such as the role of iron supplementation,” said Samuel Silver, MD, a member of ASH’s Committee on Practice and Professor of Internal Medicine at the University of Michigan. “These are issues that confront practicing hematologists and oncologists on a daily basis, and we hope that these evidence-based recommendations will influence practice standards and result in better care for patients.”
For more information:
Rizzo JD, Brouwers M, Hurley P, Seidenfeld J, Arcasoy MO, Spivak JL, Bennett CL, Bohlius J, Evanchuk D, Goode MJ, Jakubowski AA, Regan DH, Somerfield MR. American Society of Clinical Oncology/American Society of Hematology Clinical Practice Guideline Update on the Use of Epoetin and Darbepoetin in Adult Patients With CancerJ Clin Oncol. 2010 Nov 20;28(33):4996-5010. Epub 2010 Oct 25.
This article was first published online at Onco'Zine - The International Cancer Network
Tuesday, October 12, 2010
Original Research, Better Insight And Practice-changing Studies Attract Record Number Of Oncologists To Attend ESMO 2010
“The 35th ESMO Congress is milestone in our Society’s history. It has been, not only our biggest, but also our best congress ever,” declared ESMO President David J. Kerr at the event’s closing conference today. 16,000 delegates attended the European Society for Medical Oncology (ESMO) congress in Milan this week, including over 13,000 medical oncologists, 380 members of the press and close to 400 patients who participated in a dedicated seminar.
“We believe this success is due to the excellent program that the ESMO Scientific Committee put together this year, including a large amount of original research,” said Prof Kerr.
Prof Fortunato Ciardiello highlighted as one of the most important clinical studies reported here the results of a large randomized Phase-III trial in prostate cancer patients who had previously failed hormone and chemotherapy. The study was presented by researcher Johann de Bono. “These findings will change daily practice in the treatment of prostate cancer, in particular because they offer a novel and well-tolerated hormone therapy to patients for which no other treatment options were available. They contribute to a new era in drugs for prostate cancer,” said Prof Ciardiello.
Other practice-changing trials presented at the 35th ESMO Congress include a Chinese study that brings new hope to lung cancer patients (OPTIMAL trial). Lung cancer is the most common and deadliest cancer, but advances presented by Prof Caicun Zhou tripled the time people lived without the disease getting worse. An encouraging trial for ovarian cancer patients (ICON 7) presented by DrTim Perren from the UK, also attracted a lot of attention. In the field of advanced breast cancer, an American study (TDM4450g) that presented a new type of medicine with much lower toxicity compared to the older 'standard' drew a lot of interest. Principal investigator, Dr Edith Perez said the compound had shown to be effective in patients whose metastatic breast cancer had not responded to other treatments.
Prof Kerr said that what has become clear “is that we need to get back to our laboratories to understand more about the disease. We need more biology and a better insight so that we can treat the right patient, at the right time, with the right drug at the right dose.
More Information:
Visit Onco'Zine The International Cancer Network for an overview of the daily news from ESMO 2010 conference.
“We believe this success is due to the excellent program that the ESMO Scientific Committee put together this year, including a large amount of original research,” said Prof Kerr.
Prof Fortunato Ciardiello highlighted as one of the most important clinical studies reported here the results of a large randomized Phase-III trial in prostate cancer patients who had previously failed hormone and chemotherapy. The study was presented by researcher Johann de Bono. “These findings will change daily practice in the treatment of prostate cancer, in particular because they offer a novel and well-tolerated hormone therapy to patients for which no other treatment options were available. They contribute to a new era in drugs for prostate cancer,” said Prof Ciardiello.
Other practice-changing trials presented at the 35th ESMO Congress include a Chinese study that brings new hope to lung cancer patients (OPTIMAL trial). Lung cancer is the most common and deadliest cancer, but advances presented by Prof Caicun Zhou tripled the time people lived without the disease getting worse. An encouraging trial for ovarian cancer patients (ICON 7) presented by DrTim Perren from the UK, also attracted a lot of attention. In the field of advanced breast cancer, an American study (TDM4450g) that presented a new type of medicine with much lower toxicity compared to the older 'standard' drew a lot of interest. Principal investigator, Dr Edith Perez said the compound had shown to be effective in patients whose metastatic breast cancer had not responded to other treatments.
Prof Kerr said that what has become clear “is that we need to get back to our laboratories to understand more about the disease. We need more biology and a better insight so that we can treat the right patient, at the right time, with the right drug at the right dose.
More Information:
Visit Onco'Zine The International Cancer Network for an overview of the daily news from ESMO 2010 conference.
Friday, January 22, 2010
National Discussion on Proper Use and Support of Oral Chemotherapy in Cancer Care
The growing use of oral chemotherapeutics brings clinical benefits but also raises questions in prescribing, adherence, accessibility and long term follow-up care.
Therfore, US Oncology, Inc. partnered with the Association of Community Cancer Centers, Association of Oncology Social Work, American Society for Clinical Oncology, Community Oncology Alliance, Oncology Nursing Society and the National Patient Advocate Foundation in hosting a panel discussion on Capitol Hill to examine the benefits of oral chemotherapy in cancer care, as well as challenges in its prescribing, accessibility and adherence in the current health care system.
"US Oncology recognizes the benefits of oral chemotherapy treatments and supports their use in that many patients have benefited from their convenience; ease of administration; and in some cases, lessened side effects when compared to traditional chemotherapy," said Leonard Kalman, M.D., Chairman of US Oncology's Public Policy Steering Committee. "As more patients request this therapy option, it is critical that patients and their physicians be fully informed and supported when it comes to effective prescribing, access to care and dosing adherence. We applaud our partners in the oncology community for coming together to address this issue."
Oral Agent in Cancer Care
The panel discussion, entitled "Oral Agents in Cancer: Their Impact on the Treatment of Patients and Providers," featured perspectives from practicing medical oncologists, oncology nurses, oncology social workers and a chemotherapy patient who was unable to access her prescribed oral chemotherapy medication following an insurance coverage denial. As the panelists explained, all healthcare stakeholders must work together to ensure that these life-saving treatments are properly prescribed and administered, effectively covered and financially obtainable for patients as the oral chemotherapeutics market grows.
US Oncology's OncologyRx Care Advantage™ national oral oncology specialty pharmacy service provides this type of financial, administrative and clinical support to cancer patients in need. By working directly with various charitable foundations, the program has provided more than $15 million in drug co-pay assistance to cancer patients since its inception in August 2006. OncologyRx Care Advantage also provides home delivery of prescribed oral cancer therapies, utilizes oncology certified nurses to proactively monitor patient compliance and help manage side effects, and gives patients 24-hour access to oncology certified pharmacists to answer their medication and dosing questions.
Patient Adherence
With intravenous chemotherapy, cancer care providers are able to monitor treatment on site and ensure that patients properly follow to their dosing amount and schedule. However, when patients take their own oral chemotherapy treatments at home, other factors may come into play, such as forgotten doses, omitted doses, emotional factors and other priorities. Adequate patient education and follow-up are critical to make certain patients receive the full treatment they need.
Healthcare providers play a unique and important role in assisting patients' healthy behavior changes. Panelists noted that widespread success in oral chemotherapy treatment will call for improved patient access to treatments; a new level of integration in care among physicians, pharmacists and other clinicians involved with the patient's care; and a new infrastructure in care for prescribing, education and support.
The problem of poor adherence has been a well-recognized problem [1,2,3,4]. Research investigating the effects of nonadherence suggest that in the United States alone, every year more than 125,000 deaths are caused by this phenomenon, accounting for upwards of 10% to 25% of all hospital and nursing home admissions. [5]. These numbers suggest that a patient’s poor or nonadherence is one of the largest and most expensive disease categories in the US. But patient nonadherence is not limited to medications alone. Patients may ‘forget’ to keep their appointments, to follow recommended dietary, adhere to other lifestyle changes, or fail to follow – in some case deliberately sabotage - other aspects of treatment or recommended preventive health practices. As a result, the actual implications of nonadherence go far beyond the financial aspect of patients’ failing to take medication.
"As more cancer patients are likely to look to oral chemotherapy as a more convenient and less invasive treatment option, we need to ensure that systematically, we are ready to meet their needs and providers' needs in terms of ready access to treatment; comprehensive information; and full administrative, clinical and social support throughout the course of treatment," added Dr. Kalman. "We look to the steps we have taken with OncologyRx Care Advantage as a model for this type of support, and we hope the broader healthcare community and policymakers will join us in exploring similar strategies to advance treatment success more broadly in this important area of care."
For more information
[1] Haynes RB. Introduction. In: Haynes RB, Taylor DW, Sackett DL, eds. Compliance in Health Care. Baltimore, Md: Johns Hopkins University Press; 1979:1-18.
[2] Blackwell B. Drug therapy: patient compliance. N Engl J Med. 1973;289:249-252.
[3] Fawcett J. Compliance: definitions and key issues. J Clin Psychiatry. 1995;56(suppl1):4-8.
[4]Davis MS. Variation in patients' compliance with doctors' orders: medical practice and doctor-patient interaction. Psychiatry Med. 1971;2:31-54.
[5] Smith DL. Compliance packaging: a patient education tool. Am Pharm. 1989;NS29(2):42-45, 49-53.
Also:
Therfore, US Oncology, Inc. partnered with the Association of Community Cancer Centers, Association of Oncology Social Work, American Society for Clinical Oncology, Community Oncology Alliance, Oncology Nursing Society and the National Patient Advocate Foundation in hosting a panel discussion on Capitol Hill to examine the benefits of oral chemotherapy in cancer care, as well as challenges in its prescribing, accessibility and adherence in the current health care system.
"US Oncology recognizes the benefits of oral chemotherapy treatments and supports their use in that many patients have benefited from their convenience; ease of administration; and in some cases, lessened side effects when compared to traditional chemotherapy," said Leonard Kalman, M.D., Chairman of US Oncology's Public Policy Steering Committee. "As more patients request this therapy option, it is critical that patients and their physicians be fully informed and supported when it comes to effective prescribing, access to care and dosing adherence. We applaud our partners in the oncology community for coming together to address this issue."
Oral Agent in Cancer Care
The panel discussion, entitled "Oral Agents in Cancer: Their Impact on the Treatment of Patients and Providers," featured perspectives from practicing medical oncologists, oncology nurses, oncology social workers and a chemotherapy patient who was unable to access her prescribed oral chemotherapy medication following an insurance coverage denial. As the panelists explained, all healthcare stakeholders must work together to ensure that these life-saving treatments are properly prescribed and administered, effectively covered and financially obtainable for patients as the oral chemotherapeutics market grows.
US Oncology's OncologyRx Care Advantage™ national oral oncology specialty pharmacy service provides this type of financial, administrative and clinical support to cancer patients in need. By working directly with various charitable foundations, the program has provided more than $15 million in drug co-pay assistance to cancer patients since its inception in August 2006. OncologyRx Care Advantage also provides home delivery of prescribed oral cancer therapies, utilizes oncology certified nurses to proactively monitor patient compliance and help manage side effects, and gives patients 24-hour access to oncology certified pharmacists to answer their medication and dosing questions.
Patient Adherence
With intravenous chemotherapy, cancer care providers are able to monitor treatment on site and ensure that patients properly follow to their dosing amount and schedule. However, when patients take their own oral chemotherapy treatments at home, other factors may come into play, such as forgotten doses, omitted doses, emotional factors and other priorities. Adequate patient education and follow-up are critical to make certain patients receive the full treatment they need.
Healthcare providers play a unique and important role in assisting patients' healthy behavior changes. Panelists noted that widespread success in oral chemotherapy treatment will call for improved patient access to treatments; a new level of integration in care among physicians, pharmacists and other clinicians involved with the patient's care; and a new infrastructure in care for prescribing, education and support.
The problem of poor adherence has been a well-recognized problem [1,2,3,4]. Research investigating the effects of nonadherence suggest that in the United States alone, every year more than 125,000 deaths are caused by this phenomenon, accounting for upwards of 10% to 25% of all hospital and nursing home admissions. [5]. These numbers suggest that a patient’s poor or nonadherence is one of the largest and most expensive disease categories in the US. But patient nonadherence is not limited to medications alone. Patients may ‘forget’ to keep their appointments, to follow recommended dietary, adhere to other lifestyle changes, or fail to follow – in some case deliberately sabotage - other aspects of treatment or recommended preventive health practices. As a result, the actual implications of nonadherence go far beyond the financial aspect of patients’ failing to take medication.
"As more cancer patients are likely to look to oral chemotherapy as a more convenient and less invasive treatment option, we need to ensure that systematically, we are ready to meet their needs and providers' needs in terms of ready access to treatment; comprehensive information; and full administrative, clinical and social support throughout the course of treatment," added Dr. Kalman. "We look to the steps we have taken with OncologyRx Care Advantage as a model for this type of support, and we hope the broader healthcare community and policymakers will join us in exploring similar strategies to advance treatment success more broadly in this important area of care."
For more information
[1] Haynes RB. Introduction. In: Haynes RB, Taylor DW, Sackett DL, eds. Compliance in Health Care. Baltimore, Md: Johns Hopkins University Press; 1979:1-18.
[2] Blackwell B. Drug therapy: patient compliance. N Engl J Med. 1973;289:249-252.
[3] Fawcett J. Compliance: definitions and key issues. J Clin Psychiatry. 1995;56(suppl1):4-8.
[4]Davis MS. Variation in patients' compliance with doctors' orders: medical practice and doctor-patient interaction. Psychiatry Med. 1971;2:31-54.
[5] Smith DL. Compliance packaging: a patient education tool. Am Pharm. 1989;NS29(2):42-45, 49-53.
Also:
Studies Show Benefit of Advance Detection and Treatment of Gastrointestinal Cancers
A great number of the world's preeminent gastroenterologists will gather during the seventh annual Gastrointestinal Cancers Symposium (ASCO GI) from January 22-24, 2010, at the Orlando World Center Marriott to discuss new research on the treatment of gastrointestinal cancers.
Presentations at the meeting will focus on detection and treatment of gastrointestinal cancers, which includes cancers of the colon/rectum, stomach, pancreas, esophagus, small intestine, anus and other digestive organs. More than 275,000 people in the U.S. are diagnosed with these cancers each year, and nearly 136,000 people die from them. The Gastrointestinal Cancers Symposium is co-sponsored by the American Gastroenterological Association (AGA) Institute, the American Society for Clinical Oncology (ASCO), the American Society for Radiology Oncology (ASTRO) and the Society of Surgical Oncology (SSO).
Highlights from this year Scientific Meeting include the result of four significant studies:
Simple blood test detects colorectal cancer and colorectal adenomas
A new test for blood levels of the CD24 protein is more than 90 percent sensitive and specific for detecting colorectal cancer, and more than 80 percent accurate at detecting potential precancers, called adenomas. These findings may prove useful for identifying patients who would benefit most from colonoscopy.
New test for early detection of pancreatic cancer
Researchers report on a promising immunoassay that detects early-stage pancreatic cancers with a high degree of accuracy. The assay identifies and quantifies blood levels of the PAM4 protein – a unique antigen present in almost 90 percent of pancreatic cancers and precancers. Pancreatic cancer is typically diagnosed at a late stage, when it is more difficult to treat.
Inherited gene variation predicts aggressive gastric cancer
For the first time, researchers report the identification of an inherited genetic variation – located on the CD44 gene – that is linked to increased risk of recurrence in patients with gastric (stomach) cancer.
Adjuvant XELOX chemotherapy regimen slows colon cancer progression in patients of all ages, including those 70+
Adjuvant (post-surgical) treatment with capecitabine and oxaliplatin (XELOX) is more effective than standard 5-fluorouracil and leucovorin (5-FU/LV) for slowing the progression of stage III colon cancer among patients of all ages, including those age 70 and older – findings that may prompt more aggressive treatment for older patients in otherwise good health.
“Growing understanding of molecular biology has helped us make enormous progress in screening, detection and treatment for gastrointestinal cancers,” said Robert P. Sticca, MD, Chairman of the Department of Surgery and Professor at the University of North Dakota School of Medicine and Health Sciences. “These studies describe long-awaited approaches, such as an early detection test for pancreatic cancer and a blood test for colon cancer. Other studies presented during the annual symposium will help us to better personalize treatment for gastric and colon cancers based on patients’ age and genetic factors.”
Also:
Presentations at the meeting will focus on detection and treatment of gastrointestinal cancers, which includes cancers of the colon/rectum, stomach, pancreas, esophagus, small intestine, anus and other digestive organs. More than 275,000 people in the U.S. are diagnosed with these cancers each year, and nearly 136,000 people die from them. The Gastrointestinal Cancers Symposium is co-sponsored by the American Gastroenterological Association (AGA) Institute, the American Society for Clinical Oncology (ASCO), the American Society for Radiology Oncology (ASTRO) and the Society of Surgical Oncology (SSO).
Highlights from this year Scientific Meeting include the result of four significant studies:
Simple blood test detects colorectal cancer and colorectal adenomas
A new test for blood levels of the CD24 protein is more than 90 percent sensitive and specific for detecting colorectal cancer, and more than 80 percent accurate at detecting potential precancers, called adenomas. These findings may prove useful for identifying patients who would benefit most from colonoscopy.
New test for early detection of pancreatic cancer
Researchers report on a promising immunoassay that detects early-stage pancreatic cancers with a high degree of accuracy. The assay identifies and quantifies blood levels of the PAM4 protein – a unique antigen present in almost 90 percent of pancreatic cancers and precancers. Pancreatic cancer is typically diagnosed at a late stage, when it is more difficult to treat.
Inherited gene variation predicts aggressive gastric cancer
For the first time, researchers report the identification of an inherited genetic variation – located on the CD44 gene – that is linked to increased risk of recurrence in patients with gastric (stomach) cancer.
Adjuvant XELOX chemotherapy regimen slows colon cancer progression in patients of all ages, including those 70+
Adjuvant (post-surgical) treatment with capecitabine and oxaliplatin (XELOX) is more effective than standard 5-fluorouracil and leucovorin (5-FU/LV) for slowing the progression of stage III colon cancer among patients of all ages, including those age 70 and older – findings that may prompt more aggressive treatment for older patients in otherwise good health.
“Growing understanding of molecular biology has helped us make enormous progress in screening, detection and treatment for gastrointestinal cancers,” said Robert P. Sticca, MD, Chairman of the Department of Surgery and Professor at the University of North Dakota School of Medicine and Health Sciences. “These studies describe long-awaited approaches, such as an early detection test for pancreatic cancer and a blood test for colon cancer. Other studies presented during the annual symposium will help us to better personalize treatment for gastric and colon cancers based on patients’ age and genetic factors.”
Also:
Thursday, December 17, 2009
Brachytherapy Used for the First Time in United States to Treat Lung Cancer
A 58-year-old man who lives in Corona, Queens came to the emergency room of New York Hospital Queens (NYHQ) with extreme pain and tingling in his left arm. Although he did not realize it at the time, he had lung cancer. Recently, he made medical history as the first patient in the United States to be treated for lung cancer through the use of radioactive pellets placed directly in the tumor, and today his recovery is going well. Known as brachytherapy, this treatment approach is commonly used to treat prostate cancer.
"Although the patient came in because of pain in his arm, it was not due to an injury. It was discovered that the cause was a Pancoast tumor, a tumor in the lungs that affects the arms and shoulders but rarely causes symptoms, such as cough or shortness of breath, typically associated with the lungs," according to Dattatreyudu Nori, M.D., chairman, Radiation Oncology and one of the world's leading authorities in the subspecialty of brachytherapy.
Pancoast tumors form at the extreme pulmonary apex of either the right or left lung in the superior sulcus. The initial symptom is severe and constant pain in the shoulder, inner part of the scapula, or both.
In addition to general cancer symptoms such as malaise, fever, weight loss and fatigue, pancoast tumor may include a complete Horner’s syndrome caused by damage to the sympathetic nervous system, and in severe and progressive cases, miosis, anhidrosis, ptosis, and brachial plexus.
Dr Nori was the first physician in the United States to work with a computerized brachytherapy treatment system and was instrumental in the development and successful application of it to combat cancer.
The patient was treated with high dose chemotherapy and then underwent treatment with external beam radiation. Although he did have some positive response, the tumor was still present. Because of the location of the tumor, the NYHQ physicians knew that additional conventional treatment could endanger surrounding critical structures including nerves and vessels, and could affect the other organs of his body.
With the options becoming limited, Dr. Nori, along with colleague Paul C. Lee, M.D., the hospital's vice chairman of cardiothoracic surgery, decided to perform a surgical resection of the tumor and then implanted the tumor bed with radioactive Cesium 131 pellets - in a new type of brachytherapy procedure. Brachytherapy involves the implantation of radioactive seeds into the tumor site to kill the remaining cancer cells after surgical resection, while limiting the damage to healthy tissue. Brachytherapy has been successful in treating prostate cancer, but had never been used to treat this form of aggressive lung cancer.
"The tumor was very aggressive. We decided to use radioactive Cesium-131 pellets due to their high success rate in treating prostate cancer. This patient has responded well to the treatment, with an outcome that would not have been possible with traditional treatment," reports Dr. Nori.
According to Dr. Nori, Cesium-131 pellets have several advantages over the older radioactive isotopes including a shorter half-life, which means faster delivery of a radiation dose that allows less time and opportunity for the cancer cells to repopulate.
Dr. Nori has trained several hundred physicians in the U.S. on the use of brachytherapy procedures in the treatment of cancer, and more recently on the use of Cesium-131 in lung cancer treatment. He is renowned in the field of radiation oncology and for pioneering the use of use of radioactive isotopes to treat prostate cancer. He was one of the first to use the radioactive isotopes Iodine-125 and Palladium-103 in 1975 and 1985 as well as Cesium-131, which was approved by the U.S. Food and Drug Administration (FDA) in 2003 for treating prostate and other cancers.
New York Hospital Queens is a member of the New York-Presbyterian Healthcare System and an affiliate of the Weill Medical College of Cornell University.
For more information:
"Although the patient came in because of pain in his arm, it was not due to an injury. It was discovered that the cause was a Pancoast tumor, a tumor in the lungs that affects the arms and shoulders but rarely causes symptoms, such as cough or shortness of breath, typically associated with the lungs," according to Dattatreyudu Nori, M.D., chairman, Radiation Oncology and one of the world's leading authorities in the subspecialty of brachytherapy.
Pancoast tumors form at the extreme pulmonary apex of either the right or left lung in the superior sulcus. The initial symptom is severe and constant pain in the shoulder, inner part of the scapula, or both.
In addition to general cancer symptoms such as malaise, fever, weight loss and fatigue, pancoast tumor may include a complete Horner’s syndrome caused by damage to the sympathetic nervous system, and in severe and progressive cases, miosis, anhidrosis, ptosis, and brachial plexus.
Dr Nori was the first physician in the United States to work with a computerized brachytherapy treatment system and was instrumental in the development and successful application of it to combat cancer.
The patient was treated with high dose chemotherapy and then underwent treatment with external beam radiation. Although he did have some positive response, the tumor was still present. Because of the location of the tumor, the NYHQ physicians knew that additional conventional treatment could endanger surrounding critical structures including nerves and vessels, and could affect the other organs of his body.
With the options becoming limited, Dr. Nori, along with colleague Paul C. Lee, M.D., the hospital's vice chairman of cardiothoracic surgery, decided to perform a surgical resection of the tumor and then implanted the tumor bed with radioactive Cesium 131 pellets - in a new type of brachytherapy procedure. Brachytherapy involves the implantation of radioactive seeds into the tumor site to kill the remaining cancer cells after surgical resection, while limiting the damage to healthy tissue. Brachytherapy has been successful in treating prostate cancer, but had never been used to treat this form of aggressive lung cancer.
"The tumor was very aggressive. We decided to use radioactive Cesium-131 pellets due to their high success rate in treating prostate cancer. This patient has responded well to the treatment, with an outcome that would not have been possible with traditional treatment," reports Dr. Nori.
According to Dr. Nori, Cesium-131 pellets have several advantages over the older radioactive isotopes including a shorter half-life, which means faster delivery of a radiation dose that allows less time and opportunity for the cancer cells to repopulate.
Dr. Nori has trained several hundred physicians in the U.S. on the use of brachytherapy procedures in the treatment of cancer, and more recently on the use of Cesium-131 in lung cancer treatment. He is renowned in the field of radiation oncology and for pioneering the use of use of radioactive isotopes to treat prostate cancer. He was one of the first to use the radioactive isotopes Iodine-125 and Palladium-103 in 1975 and 1985 as well as Cesium-131, which was approved by the U.S. Food and Drug Administration (FDA) in 2003 for treating prostate and other cancers.
New York Hospital Queens is a member of the New York-Presbyterian Healthcare System and an affiliate of the Weill Medical College of Cornell University.
For more information:
- Ziyade S, Soysal O, Ugurlucan M, Yediyildiz S. Pancoast hydatid cyst leading to horner syndrome: thoracic hydatidosis. Heart Lung Circ. 2009 Oct;18(5):363-4. Epub 2008 Jul 26.
- Fontinele e Silva J, Barbosa Mde P, Viegas CL. Small cell carcinoma in Pancoast syndrome J Bras Pneumol. 2009 Feb;35(2):190-3.
- Nag S, Kelly JF, Horton JL, Komaki R, Nori D. Brachytherapy for carcinoma of the lung. Oncology (Williston Park). 2001 Mar;15(3):371-81.
- Hilaris BS, Martini N, Wong GY, Nori D. Treatment of superior sulcus tumor (Pancoast tumor). Surg Clin North Am. 1987 Oct;67(5):965-77.
Tuesday, December 15, 2009
Oral Bisphosphonates May Significantly Reduce Breast Cancer
Results of a new analysis of data from the Women's Health Initiative (WHI) observational study showed that women who used bisphosphonates, which are commonly prescribed bone-strengthening pills, had significantly fewer invasive breast cancers than women who did not use bisphosphonates. These findings were presented at the CRTC-AACR San Antonio Breast Cancer Symposium.
In the 150,000-plus cohort of generally healthy postmenopausal women, the researchers found that women who used bisphosphonates, mostly alendronate, which is sold as Fosamax (alendronate sodium) by Merck, had 32% fewer cases of invasive breast cancer compared to women who did not use such drugs.
"The idea that bisphosphonates could reduce breast cancer incidence is very exciting because there are about 30 million prescriptions for these agents written annually in the United States targeting bone health, and more could easily be used to counteract both osteoporosis and breast cancer," said the study's lead investigator, Rowan Chlebowski, M.D., Ph.D., medical oncologist at the Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles Medical Center.
The concept arose from findings in a report on an adjuvant breast cancer trial where use of the bisphosphonate zoledronic acid given intravenously every six months resulted in fewer contralateral breast cancers.
"It appeared to make bone less hospitable to breast cancer," Chlebowski said.
However, since bisphosphonates are prescribed for women with low bone mineral density and low bone mineral density has been associated with lower breast cancer incidence, a means to control for potential differences between women prescribed bisphosphonate and those not prescribed bisphosphonate in the cohort was needed.
Given that, Chlebowski and colleagues devised a way to control for use of bisphosphonates in the WHI. About 10,000 of the participants had bone mineral density analysis as part of the study, and for the rest they used a 10-item hip fracture predictive score to measure bone density. The researchers were able to correlate the findings from the women who had bone mineral density tests to findings from the predictive score in order to correct for any potential difference in bone density in women using bisphosphonates compared to non-users.
Studying 2,216 WHI participants who were using bisphosphonates when they entered the study, the researchers found that only 64 women developed breast cancer, and most of those cases (50) were estrogen receptor positive. Overall, there was a mean 32 percent fewer breast cancers in women using bisphosphonates compared to women who did not. There were 30 percent fewer estrogen receptor-positive cancers and 34 percent fewer entry receptor-negative cancers in bisphosphonate users. The latter finding was not statistically significant as there were very few receptor-negative cases.
"Bisphosphonates reduce angiogenesis and stimulate immune cells responsible for tumor cell surveillance as potential mediators," Chlebowski said. "This association needs to be studied further. While we currently have several options for reducing receptor-positive breast cancers, none are available for receptor-negative cancers."
Several ongoing adjuvant breast cancer trials evaluating oral and intravenous bisphosphonate will be available in the near future to provide randomized clinical trial evidence regarding their influence on new contralateral breast cancer risk, Chlebowski said.
For more information:
In the 150,000-plus cohort of generally healthy postmenopausal women, the researchers found that women who used bisphosphonates, mostly alendronate, which is sold as Fosamax (alendronate sodium) by Merck, had 32% fewer cases of invasive breast cancer compared to women who did not use such drugs.
"The idea that bisphosphonates could reduce breast cancer incidence is very exciting because there are about 30 million prescriptions for these agents written annually in the United States targeting bone health, and more could easily be used to counteract both osteoporosis and breast cancer," said the study's lead investigator, Rowan Chlebowski, M.D., Ph.D., medical oncologist at the Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles Medical Center.
The concept arose from findings in a report on an adjuvant breast cancer trial where use of the bisphosphonate zoledronic acid given intravenously every six months resulted in fewer contralateral breast cancers.
"It appeared to make bone less hospitable to breast cancer," Chlebowski said.
However, since bisphosphonates are prescribed for women with low bone mineral density and low bone mineral density has been associated with lower breast cancer incidence, a means to control for potential differences between women prescribed bisphosphonate and those not prescribed bisphosphonate in the cohort was needed.
Given that, Chlebowski and colleagues devised a way to control for use of bisphosphonates in the WHI. About 10,000 of the participants had bone mineral density analysis as part of the study, and for the rest they used a 10-item hip fracture predictive score to measure bone density. The researchers were able to correlate the findings from the women who had bone mineral density tests to findings from the predictive score in order to correct for any potential difference in bone density in women using bisphosphonates compared to non-users.
Studying 2,216 WHI participants who were using bisphosphonates when they entered the study, the researchers found that only 64 women developed breast cancer, and most of those cases (50) were estrogen receptor positive. Overall, there was a mean 32 percent fewer breast cancers in women using bisphosphonates compared to women who did not. There were 30 percent fewer estrogen receptor-positive cancers and 34 percent fewer entry receptor-negative cancers in bisphosphonate users. The latter finding was not statistically significant as there were very few receptor-negative cases.
Several ongoing adjuvant breast cancer trials evaluating oral and intravenous bisphosphonate will be available in the near future to provide randomized clinical trial evidence regarding their influence on new contralateral breast cancer risk, Chlebowski said.
For more information:
Bisphosphonates and the Risk of Postmenopausal Breast Cancer
Bisphosphonates are routinely given to women with postmenopausal breast cancer, but new data suggest that these agents may play an important role in reducing recurrent breast cancer as well. Results of a new trial demonstrated that the use of bisphosphonates was associated with a 29% reduction in the risk of postmenopausal breast cancer. The results were presented at the CTRC-AACR San Antonio Breast Cancer Symposium.
Link between Bisphosphonates and Breast Cancer
When breast cancer metastasizes, it often spreads first to the bones. Bone metastases can lead to complications such as pain, fractures, spinal cord compression, bone marrow suppression, and hypercalcemia. The primary reason for this link is that breast cancer cells stimulate bone cells called osteoclasts, and these osteoclasts in turn stimulate the growth of breast cancer cells.
Bisphosphonates have emerged as a highly effective therapeutic option for the prevention of skeletal complications secondary to bone metastases. They interrupt the relationship between osteoclasts and breast cancer cells in early stage breast cancer, slowing the progression of bone metastases while, at the same time, reducing the skeletal complications in women with metastatic breast cancer. Research has also demonstrated that bisphosphonates may prevent the development of bone metastases in newly diagnosed patients with no evidence of metastasis.
A number of agents are now approved in both Europe and the US. They included Clodronate, Pamidronate, Ibandronate, Zoledronic acid.
New and ongoing research
Lead researcher Gad Rennert, M.D., Ph.D., chairman of the Department of Community Medicine and Epidemiology at the Carmel Medical Center of Clalit Health Services and a faculty member at the Technion-Israel Institute of Technology in Israel, said these data help shed light on a possible new pathway for breast cancer prevention.
"We have identified a new class of drugs that is associated with a reduced risk of breast cancer, and if proven in randomized trials, we may be able to recommend it to postmenopausal women for this purpose," said Rennert.
Rennert and colleagues extracted data from the Breast Cancer in Northern Israel Study, which is a population-based, case-control study. They evaluated the use of bisphosphonates for at least five years in 4,575 postmenopausal study participants using a structured interview. The self-reported, long-term use of bisphosphonates prior to diagnosis was associated with a significant reduced relative risk for breast cancer by approximately 34%.
This reduction remained significant, at 29%, even after adjusting for a large variety of risk factors for breast cancer such as age, fruit and vegetable consumption, sports activity, family history of breast cancer, ethnic group, body mass index, calcium supplement and hormone replacement therapy use, number of pregnancies, months of breastfeeding and age at first pregnancy.
Moreover, the breast tumors identified among patients who used bisphosphonates were more often estrogen receptor positive and less often poorly differentiated.
"These tumors are the type that are associated with a better prognosis," said Rennert.
While most experts are cautiously optimistic about the results of this study, several of them said that more information is necessary, and as of now, they would not suggest the use of bisphosphonates for women who do not have osteoporosis.
For more information:
Link between Bisphosphonates and Breast Cancer
When breast cancer metastasizes, it often spreads first to the bones. Bone metastases can lead to complications such as pain, fractures, spinal cord compression, bone marrow suppression, and hypercalcemia. The primary reason for this link is that breast cancer cells stimulate bone cells called osteoclasts, and these osteoclasts in turn stimulate the growth of breast cancer cells.
Bisphosphonates have emerged as a highly effective therapeutic option for the prevention of skeletal complications secondary to bone metastases. They interrupt the relationship between osteoclasts and breast cancer cells in early stage breast cancer, slowing the progression of bone metastases while, at the same time, reducing the skeletal complications in women with metastatic breast cancer. Research has also demonstrated that bisphosphonates may prevent the development of bone metastases in newly diagnosed patients with no evidence of metastasis.
A number of agents are now approved in both Europe and the US. They included Clodronate, Pamidronate, Ibandronate, Zoledronic acid.
New and ongoing research
Lead researcher Gad Rennert, M.D., Ph.D., chairman of the Department of Community Medicine and Epidemiology at the Carmel Medical Center of Clalit Health Services and a faculty member at the Technion-Israel Institute of Technology in Israel, said these data help shed light on a possible new pathway for breast cancer prevention.
"We have identified a new class of drugs that is associated with a reduced risk of breast cancer, and if proven in randomized trials, we may be able to recommend it to postmenopausal women for this purpose," said Rennert.
Rennert and colleagues extracted data from the Breast Cancer in Northern Israel Study, which is a population-based, case-control study. They evaluated the use of bisphosphonates for at least five years in 4,575 postmenopausal study participants using a structured interview. The self-reported, long-term use of bisphosphonates prior to diagnosis was associated with a significant reduced relative risk for breast cancer by approximately 34%.
This reduction remained significant, at 29%, even after adjusting for a large variety of risk factors for breast cancer such as age, fruit and vegetable consumption, sports activity, family history of breast cancer, ethnic group, body mass index, calcium supplement and hormone replacement therapy use, number of pregnancies, months of breastfeeding and age at first pregnancy.
Moreover, the breast tumors identified among patients who used bisphosphonates were more often estrogen receptor positive and less often poorly differentiated.
"These tumors are the type that are associated with a better prognosis," said Rennert.
While most experts are cautiously optimistic about the results of this study, several of them said that more information is necessary, and as of now, they would not suggest the use of bisphosphonates for women who do not have osteoporosis.
For more information:
- Coleman RE. Bisphosphonates in breast cancer. Ann Oncol 2005 May;16(5):687-95. Epub 2005 Mar 31.
- Logman JF, Heeg BM, Botteman MF, Kaura S, van Hout BA. Economic evaluation of zoledronic acid for the prevention of osteoporotic fractures in postmenopausal women with early-stage breast cancer receiving aromatase inhibitors in the UK. Ann Oncol. 2009 Dec 2. [Epub ahead of print]
- Ghazi M, Roux C. Hormonal deprivation therapy-induced osteoporosis in postmenopausal women with breast cancer. Best Pract Res Clin Rheumatol. 2009 Dec;23(6):805-11.
- Theriault RL. Bisphosphonates: ready for use as adjuvant therapy of breast cancer? Curr Opin Obstet Gynecol. 2009 Nov 19. [Epub ahead of print]
Monday, December 14, 2009
New Drug Targeting Advanced Thymic Cancer May Bring Hope to Patients
The Translational Genomics Research Institute (TGen), a Phoenix, Arizona-based non-profit organization dedicated to conducting groundbreaking medical research in oncology, neurological disorders and diabetes, and Scottsdale Healthcare are testing a new drug specifically for thymic cancer. The new drug candidate is designed to stop abnormal cell division and duplication, a common feature of cancer.
The thymus, a small organ that lies in the upper chest under the breastbone or sternum. As a part of the lymph system, the thymus makes lymphocytes that protect the body against infections.
There are different types of tumors of the thymus. Both thymomas (or Thymic epithelial tumors) with clearcut cytologic features of malignancy and thymic carcinomas are rare tumors of the cells that are on the outside surface of the thymus. The tumor cells in a thymoma look similar to the normal cells of the thymus, grow slowly, and rarely spread beyond the thymus. On the other hand, the tumor cells in a thymic carcinoma look very different from the normal cells of the thymus, grow more quickly, and have usually spread to other parts of the body when the cancer is found. Thymic carcinoma is more difficult to treat than thymoma.
At the time of diagnosis, thymic carcinoma has usually metastasized. This can make formulating a treatment plan more challenging. Surgical removal of the tumor is usually the first line of therapy. Depending on the stage of the cancer at diagnosis, chemotherapy, hormone therapy, and radiation may also be prescribed. The 10-year survival rate for patients diagnosed with thymic carcinoma is approximately 28%.
Thymic carcinoma often goes unnoticed until the tumor begins to press on the patient's windpipe. It can also produce hormones that frequently cause symptoms. These may include a persistent cough, asthma, swelling of the face, diarrhea, red and warm skin, and chest pain. Some patients may have no symptoms of the cancer at all. In these cases, the tumor may have been an incidental finding on a routine chest x-ray.
Preliminary results of PHA-848125AC, a TRK A antagonist pro, is uced by Nerviano Medical Sciences of Milan, Italy’s largest pharmaceutical research and development facility, showed favorable results in treating the disease.
“From the initial trial in patients with advanced cancers, this drug is well tolerated. We are now focusing on thymic cancer based on our initial results, to hopefully find a treatment that is successful for this rare cancer - where there is no standard approved treatment,” said Dr. Glen J. Weiss, principal investigator for this trial and Director of Thoracic Oncology at TGen Clinical Research Services (TCRS) at Scottsdale Healthcare.
TCRS is a partnership between TGen and Scottsdale Healthcare that enables laboratory discoveries to be quickly turned into targeted therapies that can be tested with patients at the Virginia G. Piper Cancer Center in Scottsdale.
This Phase II clinical trial of as many as 60 adults with advanced thymic cancer will help determine if PHA-848125AC is an active drug for this disease. The thymus is a small organ near the lungs and heart that is a key part of the body’s immune system during fetal and childhood development.
Dr. Jeffrey Isaacs of Southwest Hematology Oncology in Phoenix, has seen first-hand how this agent made a difference for patients with thymic cancer. He said he is enthusiastic about a drug specifically targeting this rare cancer population to hopefully improve their outcomes.
PHA-848125AC will be administered orally. The study will be open at Scottsdale Healthcare, the Institute Gustave Roussy and the Hopital Larrey in France and at the University of Turin, San Luigi Hospital in Italy.
The intent of the study is to assess the antitumor activity of PHA-848125AC as second-line treatment in patients with recurrent or metastatic, unresectable thymic carcinoma previously treated with chemotherapy. Patients will receive 150 mg/day once daily, for 7 consecutive days (days 1 to 7) followed by 7 days of rest (days 8 to 14) in a 2-week cycle until disease progression or unacceptable toxicity will develop.
For more information about current clinical trials:
The thymus, a small organ that lies in the upper chest under the breastbone or sternum. As a part of the lymph system, the thymus makes lymphocytes that protect the body against infections.
There are different types of tumors of the thymus. Both thymomas (or Thymic epithelial tumors) with clearcut cytologic features of malignancy and thymic carcinomas are rare tumors of the cells that are on the outside surface of the thymus. The tumor cells in a thymoma look similar to the normal cells of the thymus, grow slowly, and rarely spread beyond the thymus. On the other hand, the tumor cells in a thymic carcinoma look very different from the normal cells of the thymus, grow more quickly, and have usually spread to other parts of the body when the cancer is found. Thymic carcinoma is more difficult to treat than thymoma.
At the time of diagnosis, thymic carcinoma has usually metastasized. This can make formulating a treatment plan more challenging. Surgical removal of the tumor is usually the first line of therapy. Depending on the stage of the cancer at diagnosis, chemotherapy, hormone therapy, and radiation may also be prescribed. The 10-year survival rate for patients diagnosed with thymic carcinoma is approximately 28%.
Thymic carcinoma often goes unnoticed until the tumor begins to press on the patient's windpipe. It can also produce hormones that frequently cause symptoms. These may include a persistent cough, asthma, swelling of the face, diarrhea, red and warm skin, and chest pain. Some patients may have no symptoms of the cancer at all. In these cases, the tumor may have been an incidental finding on a routine chest x-ray.
Preliminary results of PHA-848125AC, a TRK A antagonist pro, is uced by Nerviano Medical Sciences of Milan, Italy’s largest pharmaceutical research and development facility, showed favorable results in treating the disease.
“From the initial trial in patients with advanced cancers, this drug is well tolerated. We are now focusing on thymic cancer based on our initial results, to hopefully find a treatment that is successful for this rare cancer - where there is no standard approved treatment,” said Dr. Glen J. Weiss, principal investigator for this trial and Director of Thoracic Oncology at TGen Clinical Research Services (TCRS) at Scottsdale Healthcare.
TCRS is a partnership between TGen and Scottsdale Healthcare that enables laboratory discoveries to be quickly turned into targeted therapies that can be tested with patients at the Virginia G. Piper Cancer Center in Scottsdale.
This Phase II clinical trial of as many as 60 adults with advanced thymic cancer will help determine if PHA-848125AC is an active drug for this disease. The thymus is a small organ near the lungs and heart that is a key part of the body’s immune system during fetal and childhood development.
Dr. Jeffrey Isaacs of Southwest Hematology Oncology in Phoenix, has seen first-hand how this agent made a difference for patients with thymic cancer. He said he is enthusiastic about a drug specifically targeting this rare cancer population to hopefully improve their outcomes.
PHA-848125AC will be administered orally. The study will be open at Scottsdale Healthcare, the Institute Gustave Roussy and the Hopital Larrey in France and at the University of Turin, San Luigi Hospital in Italy.
The intent of the study is to assess the antitumor activity of PHA-848125AC as second-line treatment in patients with recurrent or metastatic, unresectable thymic carcinoma previously treated with chemotherapy. Patients will receive 150 mg/day once daily, for 7 consecutive days (days 1 to 7) followed by 7 days of rest (days 8 to 14) in a 2-week cycle until disease progression or unacceptable toxicity will develop.
For more information about current clinical trials:
- Phase II Study Of Oral PHA-848125AC In Patients With Thymic Carcinoma
- Johnson S B et al. Thymoma: Update for the new millennium. The Oncologist. Vol. 6, No 3, 239- 246, June 2001.
- Lara, Jr P N (2000) Malignant thymoma: current status and future directions. Cancer Treatment Reviews April 2000; 26: 2 127-131.
- Detterbeck FC, Parsons A M Thymic Tumours. The Annals of Thoracic Surgery 2004; 77:1860- 9.
- Eng T et al (2003) Thymic carcinoma: state of the art review. International Journal of Radiation Oncology Biology Physics. Vol 59 No 3.
- Giaccone G Treatment of malignant thymoma. Current Opinion in Oncology 2005 17: 140- 146.
- World Health Organisation classification of tumours. Pathology and genetics. Tumours of the lung, pleura, thymus and heart. World Health Organisation Classification of Tumours Vol.10 Eds. Travis WD et al. WHO Press, 2004.
- Textbook of Uncommon Cancer (3rd edition) Eds. Raghavan et al. Wiley, 2006.
- Nakagawara A Trk receptor tyrosine kinases: a bridge between cancer and neural development Cancer Lett.2001 Aug 28;169(2):107-14.
- Mitsutake N, Yamashita S The role of cancer genes in thyroid cancer and molecular targeted therapy Nippon Naika Gakkai Zasshi. 2009 Aug 10;98(8):1999-2005.
Saturday, December 12, 2009
DM1, an Investigational Antibody-Drug Conjugate, Shows Encouraging Results in Women With Highly Advanced HER2-positive Breast Cancer
Results of a Phase II study of trastuzumab (Herceptin®, Genentech) in combination with DM1 (T-DM1), an investigational HER2 antibody-drug conjugate being developed by Genentech, in collaboration with Roche and Immunogen, Inc., shows encouraging results in women with highly advanced HER2-positive breast cancer.
Positive Phase I and Phase II findings were first reported at the 2007 [1] and 2008 [2], respectively, annual meetings of the American Society of Clinical Oncology (ASCO) with T-DM1 in patients with HER2-positive (HER2+) metastatic breast cancer (MBC) that progressed on treatment with trastuzumab. In the Phase II study, 60% of patients also had been treated with lapatinib (Tykerb®, GlaxoSmithKline).
Women in this study had already received an average of seven drugs for metastatic disease, including chemotherapy, trastuzumab and lapatinib, prior to receiving T-DM1. No new or unexpected safety signals were observed. The results were presented today at the 32nd Annual CTRC-AACR San Antonio Breast Cancer Symposium (SABCS) from 9 to 13 December 2009 (Abstract #710). [3]
“Breast cancer is the most common cancer among women worldwide with more than one million new cases diagnosed every year and nearly 400,000 deaths, so it is vital that we continue to provide more treatment options” said William M. Burns, CEO of Roche Pharma.
According to the American Cancer Society [6], breast cancer is the second leading cause of cancer death in the United States. Women diagnosed with advanced (metastatic) disease have a poor prognosis and only 27% survive five years.
Approximately 15 to 30% of breast cancers are HER2-positive. [7] When HER2-positive breast cancer is advanced, the disease has spread to other parts of the body, most commonly to the lungs, bones, liver and brain. At this stage of the disease, the current goals of existing treatments include symptom relief, tumor shrinkage, improved quality of life and increasing the amount of time women with advanced breast cancer live without the cancer worsening. There are no treatment guidelines or FDA-approved treatment options for women with advanced HER2-positive breast cancer if the disease progresses following treatment with trastuzumab and lapatinib.
“The much anticipated data on the investigational drug T-DM1 will be welcomed by physicians treating women with early and very advanced stages of breast cancer as it will offer them more choices for fighting this devastating disease,” Burns noted.
"Despite major advances in HER2-positive breast cancer, the disease may still progress after multiple treatments, to the point where there are no approved HER2-targeted medicines," said Hal Barron, M.D., executive vice president, Global Development and chief medical officer, Genentech. "Results from this study are promising for women who need new treatment options, and we will discuss next steps of the T-DM1 development program with the FDA."
"These results are significant because they demonstrate that T-DM1 was effective at shrinking tumors in women whose cancer had progressed following prior treatment with standard therapies for HER2-positive breast cancer," said Ian Krop, M.D., Ph.D., a medical oncologist at Dana-Farber Cancer Institute, and lead investigator on the study.
In this single-arm study, 45% of women experienced a clinical benefit (defined as a complete or partial tumor response, or stable disease, maintained for at least six months), as assessed by independent review. Adverse events were similar to those observed in previous clinical trials of T-DM1. The most common severe adverse events included thrombocytopenia (a low level of platelets in the blood, 5.5%) and back pain (3.6%), and the most common adverse events were fatigue (59.1%) and nausea (37.3%). No severe (Grade 3 or higher) cardiac-specific side effects were observed. One patient with pre-existing, non-alcoholic fatty liver disease died with hepatic failure.
Ongoing clinical trials
The new treatment options is currently in trial in a Phase II study, known as TDM4374g, a single-arm, multi-center trial designed to assess T-DM1 as a single agent in 110 women with HER2-positive advanced breast cancer whose disease had progressed after receiving at least two prior HER2-targeted treatments (trastuzumab and lapatinib) in the metastatic setting, as well as an anthracycline, a taxane, and capecitabine. [8]
The primary endpoint of this study is objective response rate (a complete or partial tumor shrinkage of at least 30%, determined by two tumor assessments at least 28 days apart), as measured by an independent review facility. Secondary endpoints include safety, clinical benefit rate, duration of response and progression-free survival (PFS). Duration of response and PFS data are not yet mature and will be presented at a future meeting.
The results of the data presented during the SABCS follow on from results from another phase II study (TDM4258) presented at ASCO 2009 which also showed encouraging results in women with advanced HER2-positive breast cancer [9, 10].
For more information:
[1] Beeram M, Krop I, Modi S, Tolcher A, Rabbee N, et al A phase I study of trastuzumab-MCC-DM1 (T-DM1), a first-in-class HER2 antibody-drug conjugate (ADC), in patients (pts) with HER2+ metastatic breast cancer (BC). Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 1042.
[2] Beeram M, Burris III, HA, Modi S, Birkner M, Girish S, et al. A phase I study of trastuzumab-DM1 (T-DM1), a first-in-class HER2 antibody-drug conjugate (ADC), in patients (pts) with advanced HER2+ breast cancer (BC). J Clin Oncol 26: 2008 (May 20 suppl; abstr 1028).
[3] Krop I, LoRusso P, Miller KD, Modi S, Yardley D, et al. A Phase II Study of Trastuzumab-DM1 (T-DM1), a Novel HER2 Antibody-Drug Conjugate, in Patients Previously Treated with Lapatinib, Trastuzumab, and Chemotherapy. SABCS Poster Session 5: Treatment: Her2-Targeted Therapy (Date/Time: Saturday, December 12, 2009; 5:30 PM-7:30 PM)
[4] Teicher BA. Antibody-drug conjugate targets. Curr Cancer Drug Targets. 2009 Dec;9(8):982-1004
[5] Hofer T, Skeffington LR, Chapman CM, Rader C. Molecularly defined antibody conjugation through a selenocysteine interface. Biochemistry. 2009 Dec 22;48(50):12047-57.
[6] American Cancer Society. Breast Cancer Facts & Figures 2009-2010. Atlanta: American Cancer Society, Inc.
[7] Murphy CG, Modi S. HER2 breast cancer therapies: a review. Biologics. 2009;3:289-301. Epub 2009 Jul 13.
[8] A Study of of Trastuzumab-Mcc-DM1 Administered Intravenously to Patients With HER2-Positive Metastatic Breast Cancer.
[9] A Study of Trastuzumab-MCC-DM1 Administered Intravenously to Patients With HER2-Positive Metastatic Breast Cancer.
[10] Vogel CL, Burris HA, Limentani S, Borson R, O'Shaughnessy J, et al. A phase II study of trastuzumab-DM1 (T-DM1), a HER2 antibody-drug conjugate (ADC), in patients (pts) with HER2+ metastatic breast cancer (MBC): Final results. J Clin Oncol 27:15s, 2009 (suppl; abstr 1017).
Also:
Onco’Zine – The International Cancer Network
Positive Phase I and Phase II findings were first reported at the 2007 [1] and 2008 [2], respectively, annual meetings of the American Society of Clinical Oncology (ASCO) with T-DM1 in patients with HER2-positive (HER2+) metastatic breast cancer (MBC) that progressed on treatment with trastuzumab. In the Phase II study, 60% of patients also had been treated with lapatinib (Tykerb®, GlaxoSmithKline).
As assessed by independent review, the T-DM1 combination shrank the tumors (also known as objective response) in 33% of women with advanced (metastatic) HER2-positive breast cancer that had worsened following previous treatment.
Women in this study had already received an average of seven drugs for metastatic disease, including chemotherapy, trastuzumab and lapatinib, prior to receiving T-DM1. No new or unexpected safety signals were observed. The results were presented today at the 32nd Annual CTRC-AACR San Antonio Breast Cancer Symposium (SABCS) from 9 to 13 December 2009 (Abstract #710). [3]Antibody-drug conjugates or ADCs [4] are a unique combination of a precise and targeted monoclonal antibody, a stable linker, and a potent cytotoxic. They have broad utility in basic, preclinical, and clinical applications. [5] T-DM1 combines two approaches in one medicine: the anti-cancer activity of the trastuzumab antibody, which blocks signals that make the cancer more aggressive and signals the body’s immune system to destroy the cancerous cells, and the targeted delivery of the potent cytotoxic DM1.
“Breast cancer is the most common cancer among women worldwide with more than one million new cases diagnosed every year and nearly 400,000 deaths, so it is vital that we continue to provide more treatment options” said William M. Burns, CEO of Roche Pharma.
According to the American Cancer Society [6], breast cancer is the second leading cause of cancer death in the United States. Women diagnosed with advanced (metastatic) disease have a poor prognosis and only 27% survive five years.
Approximately 15 to 30% of breast cancers are HER2-positive. [7] When HER2-positive breast cancer is advanced, the disease has spread to other parts of the body, most commonly to the lungs, bones, liver and brain. At this stage of the disease, the current goals of existing treatments include symptom relief, tumor shrinkage, improved quality of life and increasing the amount of time women with advanced breast cancer live without the cancer worsening. There are no treatment guidelines or FDA-approved treatment options for women with advanced HER2-positive breast cancer if the disease progresses following treatment with trastuzumab and lapatinib.
“The much anticipated data on the investigational drug T-DM1 will be welcomed by physicians treating women with early and very advanced stages of breast cancer as it will offer them more choices for fighting this devastating disease,” Burns noted.
"Despite major advances in HER2-positive breast cancer, the disease may still progress after multiple treatments, to the point where there are no approved HER2-targeted medicines," said Hal Barron, M.D., executive vice president, Global Development and chief medical officer, Genentech. "Results from this study are promising for women who need new treatment options, and we will discuss next steps of the T-DM1 development program with the FDA."
"These results are significant because they demonstrate that T-DM1 was effective at shrinking tumors in women whose cancer had progressed following prior treatment with standard therapies for HER2-positive breast cancer," said Ian Krop, M.D., Ph.D., a medical oncologist at Dana-Farber Cancer Institute, and lead investigator on the study.
In this single-arm study, 45% of women experienced a clinical benefit (defined as a complete or partial tumor response, or stable disease, maintained for at least six months), as assessed by independent review. Adverse events were similar to those observed in previous clinical trials of T-DM1. The most common severe adverse events included thrombocytopenia (a low level of platelets in the blood, 5.5%) and back pain (3.6%), and the most common adverse events were fatigue (59.1%) and nausea (37.3%). No severe (Grade 3 or higher) cardiac-specific side effects were observed. One patient with pre-existing, non-alcoholic fatty liver disease died with hepatic failure.
Ongoing clinical trials
The new treatment options is currently in trial in a Phase II study, known as TDM4374g, a single-arm, multi-center trial designed to assess T-DM1 as a single agent in 110 women with HER2-positive advanced breast cancer whose disease had progressed after receiving at least two prior HER2-targeted treatments (trastuzumab and lapatinib) in the metastatic setting, as well as an anthracycline, a taxane, and capecitabine. [8]
The primary endpoint of this study is objective response rate (a complete or partial tumor shrinkage of at least 30%, determined by two tumor assessments at least 28 days apart), as measured by an independent review facility. Secondary endpoints include safety, clinical benefit rate, duration of response and progression-free survival (PFS). Duration of response and PFS data are not yet mature and will be presented at a future meeting.
The results of the data presented during the SABCS follow on from results from another phase II study (TDM4258) presented at ASCO 2009 which also showed encouraging results in women with advanced HER2-positive breast cancer [9, 10].
For more information:
[1] Beeram M, Krop I, Modi S, Tolcher A, Rabbee N, et al A phase I study of trastuzumab-MCC-DM1 (T-DM1), a first-in-class HER2 antibody-drug conjugate (ADC), in patients (pts) with HER2+ metastatic breast cancer (BC). Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 1042.
[2] Beeram M, Burris III, HA, Modi S, Birkner M, Girish S, et al. A phase I study of trastuzumab-DM1 (T-DM1), a first-in-class HER2 antibody-drug conjugate (ADC), in patients (pts) with advanced HER2+ breast cancer (BC). J Clin Oncol 26: 2008 (May 20 suppl; abstr 1028).
[3] Krop I, LoRusso P, Miller KD, Modi S, Yardley D, et al. A Phase II Study of Trastuzumab-DM1 (T-DM1), a Novel HER2 Antibody-Drug Conjugate, in Patients Previously Treated with Lapatinib, Trastuzumab, and Chemotherapy. SABCS Poster Session 5: Treatment: Her2-Targeted Therapy (Date/Time: Saturday, December 12, 2009; 5:30 PM-7:30 PM)
[4] Teicher BA. Antibody-drug conjugate targets. Curr Cancer Drug Targets. 2009 Dec;9(8):982-1004
[5] Hofer T, Skeffington LR, Chapman CM, Rader C. Molecularly defined antibody conjugation through a selenocysteine interface. Biochemistry. 2009 Dec 22;48(50):12047-57.
[6] American Cancer Society. Breast Cancer Facts & Figures 2009-2010. Atlanta: American Cancer Society, Inc.
[7] Murphy CG, Modi S. HER2 breast cancer therapies: a review. Biologics. 2009;3:289-301. Epub 2009 Jul 13.
[8] A Study of of Trastuzumab-Mcc-DM1 Administered Intravenously to Patients With HER2-Positive Metastatic Breast Cancer.
[9] A Study of Trastuzumab-MCC-DM1 Administered Intravenously to Patients With HER2-Positive Metastatic Breast Cancer.
[10] Vogel CL, Burris HA, Limentani S, Borson R, O'Shaughnessy J, et al. A phase II study of trastuzumab-DM1 (T-DM1), a HER2 antibody-drug conjugate (ADC), in patients (pts) with HER2+ metastatic breast cancer (MBC): Final results. J Clin Oncol 27:15s, 2009 (suppl; abstr 1017).
Also:
Onco’Zine – The International Cancer Network
Sunday, December 6, 2009
Targeted Breast Ultrasound Can Reduce Biopsies for Women under Forty
Targeted breast ultrasound of suspicious areas of the breast, including lumps, is a safe, reliable and cost-effective alternative to invasive biopsies for women under age 40, according to the findings of two studies presented at the 95th Scientific Assembly and Annual Meeting of the Radiological Society of North America (RSNA).
"By performing high-quality breast ultrasound, we can reduce the number of expensive and avoidable invasive diagnostic procedures in young women," said senior author Constance D. Lehman, M.D., Ph.D., professor and vice chair of radiology at the University of Washington and director of imaging at the Seattle Cancer Care Alliance. "We don’t want to be overly aggressive with this population."
The researchers conducted two studies in which targeted ultrasound was used to distinguish between potentially cancerous masses and benign findings in young women who had detected breast lumps or other focal (specific) areas of concern in their breasts. The first study included 1,123 ultrasound examinations of women under age 30, while the second included 1,577 ultrasound examinations of women ages 30 to 39.
Across both studies, all instances of cancer at the site of the clinical concern were positively identified through targeted ultrasound. In addition, all negative ultrasound findings correctly identified benign changes in the breast. The only malignant mass not identified by ultrasound was an unsuspected lesion outside of the targeted examination area. That cancer was identified by a full breast mammogram.
The incidence of malignancy among women in their 30s was 2%. The incidence of malignancy among women younger than 30 was 0.4 percent.Fig 1. A breast ultrasound image showing a benign mass.
"Surgical excision or needle biopsy of tissue can be painful, expensive and frequently unnecessary in these age groups, which have very low rates of malignancies," Dr. Lehman said. "In most cases, monitoring with targeted ultrasound is a very safe alternative."
She added that ultrasound should be the diagnostic tool of choice for young women seeking care for breast lumps and other suspicious focal signs and symptoms. "It is time we used ultrasound to reduce unnecessary morbidity and costs associated with more aggressive invasive approaches," Dr. Lehman said.
Also see Abstracts:
- Outcomes of Targeted Ultrasound Evaluation in Women Under 30 Years of Age with Focal Breast Signs or Symptoms. Presented by Dr. Vilert Loving, MD
- Contribution of Mammography to Ultrasound Evaluation of Women 30 to 39 Years of Age with Focal Breast Signs or Symptoms . Presented by Michael Portillo, MD
For more information:
- Onco'Zine - The International Cancer Network
Ultrasound with Elastography May Improve Skin Cancer Detection
High-frequency ultrasound with elastography can help differentiate between cancerous and benign skin conditions, according to a study presented at the 95th Scientific Assembly and Annual Meeting of the Radiological Society of North America (RSNA).
"High-frequency ultrasound with elastography has the potential to improve the efficiency of skin cancer diagnosis," said lead author Eliot L. Siegel, M.D., vice chairman of the Department of Radiology at the University of Maryland School of Medicine (UMSM) in Baltimore. "It successfully delineated the extent of lesions and was able to provide measurable differentiation among a variety of benign and malignant lesions."
Suspicious skin lesions are typically diagnosed by dermatologists and biopsied based on their surface appearance and characteristics. Unfortunately, even to experienced dermatologists, benign and malignant lesions often appear similar visually and on physical examination, and some malignant lesions may have a benign appearance, especially in their early stages. It is not uncommon for patients to have one or more lesions that appear concerning.
"Dermatologists tend to biopsy any lesions that seem visually suspicious for disease," said coauthor Bahar Dasgeb, M.D., from the Department of Dermatology at Wayne State University in Detroit and Pinkus Dermatopathology Lab in Monroe, Michigan. "Consequently, many benign lesions are needlessly biopsied in order to avoid the risk of missing a potentially deadly melanoma."
Elastography was found to distinguish between benign and malignant lesions not by their visible appearance but by measuring their elasticity or stiffness. Since malignancies are stiffer than benign growths, elastography, when added to high-frequency ultrasound imaging of the skin, has potential to improve the accuracy of traditional clinical diagnosis of skin cancers and, in some cases, eliminate unnecessary biopsies of benign skin lesions. The procedure is noninvasive, convenient and inexpensive.
For the study, researchers used an ultra high-frequency ultrasound system to image 40 patients with a variety of malignant and nonmalignant, or benign, skin lesions. Malignant tumors included squamous cell carcinoma, basal cell carcinoma and melanoma. Benign lesions included dermatofibroma, a noncancerous growth containing scar tissue, and lipoma, a noncancerous tumor composed of fatty tissue.The researchers calculated the ratio of elasticity between normal skin and the adjacent skin lesion, and used laboratory analysis to confirm their diagnoses. Cystic lesions, which are not malignant, demonstrated high levels of elasticity, while malignant lesions were significantly less elastic. The elasticity ratio of normal skin to the various skin lesions ranged from 0.04 to 0.3 for cystic skin lesions to above 10.0 for malignant lesions.
In addition, high-frequency ultrasound with elastography allows for accurate characterization of the extent and depth of the lesion below the surface, which can aid physicians in treatment.
Fig 2. An elastogram (left) and ultrasound image (right) showing a premalignant lesion
For more information, also see:
Elastographic Ultrasound Quantitative Analysis Combined with High Frequency Imaging for Characterization of Benign and Malignant Skin Lesions Presented by Dr. Bahar Dasgeb, MD.
Also see:
Ultrasound with Elastography May Improve Skin Cancer Detection
Saturday, October 3, 2009
New Cancer Research Priorities Needed to Correct Imbalance that Leaves Important Questions Neglected
Cancer research is too focused on new drug development, while not enough money and effort is being devoted to pursuing important advances in knowledge likely to have the biggest impact on combating the disease in the next few decades, a leading research policy expert says, adding that a major shift in research priorities will be crucial to the ability to cope with the coming wave of cancer cases.
Professor Richard Sullivan of the King’s Health Partners Integrated Cancer Centre in London told Europe’s largest cancer congress, ECCO 15 – ESMO 34, the joint 15th European CanCer Organisation (ECCO) and 34th European Society for Medical Oncology (ESMO) Multidisciplinary Congress, September 20 – 24 in Berlin, Germany, that studies aiming to improve surgery, pathology and diagnostic and staging imaging, as well as a radical rethink of the approach to prevention research, must become the focus of public- and federally-funded cancer research now. The global public sector spend on cancer research was about €14 billion a year in 2004/05, the latest year for which figures are available. Non-commercial funders in Europe spent just over €3 billion on cancer research in 2004/05.
“An analysis we have just completed shows that, on average, European public funders are spending 74% of their money on fundamental biology and drug development research and that well over 70% of the cancer research initiatives at the European level are aimed at the same areas,” noted Prof Sullivan, who is also chairman of the European Cancer Research Managers Forum, which studies cancer research and funding in Europe.
“In the United States, the imbalance is even greater. There is no shortage of cancer drugs coming through pipeline and the whole area of drug research is quite healthy. What we need is a reapportioning of budgets from the charitable sector and public funders to carve out space for these other areas of cancer research that are largely invisible to a lot of policymakers."
“This is a deeply unfashionable view and the easy way out is to say that we must just ask for more money, but the reality is that we’ve got to prioritise,” Prof Sullivan said. “Most of the new medicines are having a small impact on the big picture of cancer burden at the moment, extending life by a few months. Research in this area is already heavily funded and that will continue regardless, as will the investments in fundamental cancer biology.”
The World Health Organization predicts that the number of people worldwide living with cancer will rise from about 28 million today to about 75 million in 2030. Detecting cancer early enough to treat it successfully and improving our understanding of how to make primary prevention strategies work hold the potential for the greatest gains, he said.
“This demands an overhaul of prevention research. You can take the quite reasonable view that we know the risk factors now. What we don’t understand is how to take that research on prevention and apply it in populations because we don’t understand the behaviour of those groups or how that might change over the next 20 or 30 years. For instance, how do we address the fact that many men across Europe will put up with rectal bleeding for a year before going to see a doctor? This is very important because cancer is not just about genes, it is predominantly about culture.”
"Cancer researchers must now be more imaginative and collaborate across unusual disciplinary boundaries to embrace behavioural engineering, population psychology, evolutionary biology, novel sociological methods and ideas such as cultural transmission theory – the study of how behaviours are learned and transmitted between generations," Sullivan explained
“Research in these novel areas addresses questions that can never be answered with classical epidemiological studies or standard social science questionnaires – we’ve reached the limits of enquiry with many standard approaches. There are people doing fantastic work that could be extremely useful not only to cancer research, but to medicine in general and most medics and researchers are completely ignorant about their existence and what they can do for medicine. It is a huge untapped area with massive potential to make a difference,” Prof Sullivan said.
The growing scale of cancer in developing countries also presents an imminent challenge for cancer research, he said. More than half of all cancer diagnoses occur in developing countries, which will bear a large majority of the global burden before long. Keeping the research focus as it is in developed countries will not address the problem in the developing and transitional countries because drug development is not going to be the answer. Surgery and radiotherapy are the most important approaches for reducing the global cancer burden and financial support for programmes that bring those treatments to developing countries is still very poor.
“The argument is always made that there is enough to deal with in developing countries with the infectious disease challenges, but chronic disease is a major, often unrecognised problem and we can’t afford to wait any longer. Like it or not, developed countries have a responsibility to investigate which cancer control approaches are exportable and to support those institutions working in these areas,” he said.
Governments, research charities and European funders need to recognise the importance of shifting the focus to a new approach to prevention research and more investment in non-drug treatment research, but it will be largely up to cancer researchers to drive the change, Prof Sullivan said.
“There has already recently been a major shift in Europe toward hospital-university alliances driving the agenda. They need to start banging on the doors of the non-government organisations and the federal funders, lobbying hard and proving that it’s important to give attention to these neglected areas of cancer research.”
For more information:
Professor Richard Sullivan of the King’s Health Partners Integrated Cancer Centre in London told Europe’s largest cancer congress, ECCO 15 – ESMO 34, the joint 15th European CanCer Organisation (ECCO) and 34th European Society for Medical Oncology (ESMO) Multidisciplinary Congress, September 20 – 24 in Berlin, Germany, that studies aiming to improve surgery, pathology and diagnostic and staging imaging, as well as a radical rethink of the approach to prevention research, must become the focus of public- and federally-funded cancer research now. The global public sector spend on cancer research was about €14 billion a year in 2004/05, the latest year for which figures are available. Non-commercial funders in Europe spent just over €3 billion on cancer research in 2004/05.“An analysis we have just completed shows that, on average, European public funders are spending 74% of their money on fundamental biology and drug development research and that well over 70% of the cancer research initiatives at the European level are aimed at the same areas,” noted Prof Sullivan, who is also chairman of the European Cancer Research Managers Forum, which studies cancer research and funding in Europe.
“In the United States, the imbalance is even greater. There is no shortage of cancer drugs coming through pipeline and the whole area of drug research is quite healthy. What we need is a reapportioning of budgets from the charitable sector and public funders to carve out space for these other areas of cancer research that are largely invisible to a lot of policymakers."
“This is a deeply unfashionable view and the easy way out is to say that we must just ask for more money, but the reality is that we’ve got to prioritise,” Prof Sullivan said. “Most of the new medicines are having a small impact on the big picture of cancer burden at the moment, extending life by a few months. Research in this area is already heavily funded and that will continue regardless, as will the investments in fundamental cancer biology.”
The World Health Organization predicts that the number of people worldwide living with cancer will rise from about 28 million today to about 75 million in 2030. Detecting cancer early enough to treat it successfully and improving our understanding of how to make primary prevention strategies work hold the potential for the greatest gains, he said.
“This demands an overhaul of prevention research. You can take the quite reasonable view that we know the risk factors now. What we don’t understand is how to take that research on prevention and apply it in populations because we don’t understand the behaviour of those groups or how that might change over the next 20 or 30 years. For instance, how do we address the fact that many men across Europe will put up with rectal bleeding for a year before going to see a doctor? This is very important because cancer is not just about genes, it is predominantly about culture.”
"Cancer researchers must now be more imaginative and collaborate across unusual disciplinary boundaries to embrace behavioural engineering, population psychology, evolutionary biology, novel sociological methods and ideas such as cultural transmission theory – the study of how behaviours are learned and transmitted between generations," Sullivan explained
“Research in these novel areas addresses questions that can never be answered with classical epidemiological studies or standard social science questionnaires – we’ve reached the limits of enquiry with many standard approaches. There are people doing fantastic work that could be extremely useful not only to cancer research, but to medicine in general and most medics and researchers are completely ignorant about their existence and what they can do for medicine. It is a huge untapped area with massive potential to make a difference,” Prof Sullivan said.
The growing scale of cancer in developing countries also presents an imminent challenge for cancer research, he said. More than half of all cancer diagnoses occur in developing countries, which will bear a large majority of the global burden before long. Keeping the research focus as it is in developed countries will not address the problem in the developing and transitional countries because drug development is not going to be the answer. Surgery and radiotherapy are the most important approaches for reducing the global cancer burden and financial support for programmes that bring those treatments to developing countries is still very poor.
“The argument is always made that there is enough to deal with in developing countries with the infectious disease challenges, but chronic disease is a major, often unrecognised problem and we can’t afford to wait any longer. Like it or not, developed countries have a responsibility to investigate which cancer control approaches are exportable and to support those institutions working in these areas,” he said.
Governments, research charities and European funders need to recognise the importance of shifting the focus to a new approach to prevention research and more investment in non-drug treatment research, but it will be largely up to cancer researchers to drive the change, Prof Sullivan said.
“There has already recently been a major shift in Europe toward hospital-university alliances driving the agenda. They need to start banging on the doors of the non-government organisations and the federal funders, lobbying hard and proving that it’s important to give attention to these neglected areas of cancer research.”
For more information:
Monday, September 28, 2009
International Trial Shows Aspirin Protects Against Colorectal Cancer
A daily dose of aspirin can prevent the occurrence of cancer in people with a genetic predisposition towards Lynch syndrome, a condition which accounts for around five percent of all colon cancers, a scientist told the audience at Europe’s largest cancer congress, ECCO 15 – ESMO 34, the joint 15th European CanCer Organisation (ECCO) and 34th European Society for Medical Oncology (ESMO) Multidisciplinary Congress, September 20 – 24 in Berlin, Germany.
Professor John Burn, from the Institute of Human Genetics, Newcastle University, Newcastle upon Tyne, UK, said that he believed that he and his colleagues might have uncovered a simple way of controlling cancer stem cells, which are essential to the formation of malignant tumors.
The clinical trial, which involved 1071 carriers of the Lynch syndrome mutation in 42 centers worldwide, randomized participants to a daily dose of 600mg aspirin and/or 30g Novelose®, a resistant starch that escapes digestion in the small intestine. “Although there were many reports that aspirin might have a beneficial effect in a range of cancers,” said Prof Burn, “they were from case control and epidemiological studies. We decided that the only way to achieve conclusive proof was to undertake a randomized trial in a high risk population.”
Lynch syndrome, often called hereditary nonpolyposis colorectal cancer (HNPCC), is a rare type type of inherited cancer of the digestive tract that increases a patient’s risk of cancer, particularly the colon and rectum. People with Lynch syndrome have an increased risk of cancers of the stomach, small intestine, liver, gallbladder ducts, upper urinary tract, brain, skin, and prostate. Women carriers also have a high risk of developing endometrial and ovarian cancers.
These patients tend to develop cancer quickly, so the scientists expected to see answers at an early stage. The first results were disappointing, however; at an average of 29 months after randomization the scientists saw no evidence of the benefits of aspirin in the high-risk population studied.
“Our original design allowed for long term post trial follow-up,” noted Prof Burn. “We have managed to track down most of those who completed the trial – around 75% of the original consent cohort – with information extending up to 10 years from randomization. We found that, around four years after randomization, there was a divergence in the incidence of cancers between the aspirin and placebo groups. To date, there have been only six colon cancers in the aspirin group as opposed to 16 who took placebo. There is also a reduction in endometrial cancer. This is a statistically significant result and we are delighted – all the more so because we stopped giving the aspirin after four years, yet the effect is continuing, and is directly correlated with the duration of aspirin use on the trial.”
Although scientists believe that diet is a major factor in the prevention of colorectal cancers, there are no randomized trial data which can prove it, since running proper, controlled trials of diet is extremely difficult. However, there is a strong inverse relationship between colon cancer and how much starch people eat. Resistant starch, after escaping digestion in the upper gut, is fermented in the colon and forms short chain fatty acids, which are powerful anti-cancer agents.
“Our very large colon probably evolved to capture such nutrients from our forefathers’ diets,” explained Prof Burn. “Because we were giving starch as well as aspirin we would also have expected to see a decrease in cancers in the placebo group. However, there could be a number of reasons for this result – perhaps patients didn’t take the starch every day, or that it simply wasn’t resistant enough.”
There were minor problems due to aspirin side effects; out of over 1000 people, 11 in the aspirin group had notable gastro-intestinal bleeds or ulcers as opposed to nine in the placebo group. But this was counter-balanced by fewer strokes and heart attacks in the aspirin group.
The mechanism by which aspirin protects against cancer has yet to be elucidated, but the scientists believe that cancer stem cells are involved. “We do not think that the mechanisms discussed to date are likely to provide an explanation,” said Prof Burn. “For example, the inflammatory enzyme COX2(Cyclooxygenase-2), a protein that acts as an enzyme and specifically catalyzes the production of certain chemical messengers called prostaglandins, is over-expressed in early cancer, but our results suggest an effect that predates the cancer, and may even predate the adenoma which precedes it. We believe that aspirin may have an effect on the survival of aberrant stem cells in the colon. These cancer stem cells are normally resistant to chemotherapy, but if a stem cell mutates but does not reveal its potential until an adenoma is formed, and if aspirin reduced the chances of such cells surviving, this would explain our results.”
The team intends to undertake a further study to see whether a smaller dose of aspirin would have the same beneficial effect or not. “We are planning to ask people with Lynch syndrome to agree to ‘toss a coin’ and take, say, either one or two aspirin tablets per day. Then we can see whether the people on the lower dose have the same protection, with fewer side effects. The problem is that, to have a significant result, this will need about 10 times as many people as we needed for our first trial, but the good news is that everyone gets treated,” said Prof Burn.
For more information:
Professor John Burn, from the Institute of Human Genetics, Newcastle University, Newcastle upon Tyne, UK, said that he believed that he and his colleagues might have uncovered a simple way of controlling cancer stem cells, which are essential to the formation of malignant tumors.
The clinical trial, which involved 1071 carriers of the Lynch syndrome mutation in 42 centers worldwide, randomized participants to a daily dose of 600mg aspirin and/or 30g Novelose®, a resistant starch that escapes digestion in the small intestine. “Although there were many reports that aspirin might have a beneficial effect in a range of cancers,” said Prof Burn, “they were from case control and epidemiological studies. We decided that the only way to achieve conclusive proof was to undertake a randomized trial in a high risk population.”
Lynch syndrome, often called hereditary nonpolyposis colorectal cancer (HNPCC), is a rare type type of inherited cancer of the digestive tract that increases a patient’s risk of cancer, particularly the colon and rectum. People with Lynch syndrome have an increased risk of cancers of the stomach, small intestine, liver, gallbladder ducts, upper urinary tract, brain, skin, and prostate. Women carriers also have a high risk of developing endometrial and ovarian cancers.
These patients tend to develop cancer quickly, so the scientists expected to see answers at an early stage. The first results were disappointing, however; at an average of 29 months after randomization the scientists saw no evidence of the benefits of aspirin in the high-risk population studied.
“Our original design allowed for long term post trial follow-up,” noted Prof Burn. “We have managed to track down most of those who completed the trial – around 75% of the original consent cohort – with information extending up to 10 years from randomization. We found that, around four years after randomization, there was a divergence in the incidence of cancers between the aspirin and placebo groups. To date, there have been only six colon cancers in the aspirin group as opposed to 16 who took placebo. There is also a reduction in endometrial cancer. This is a statistically significant result and we are delighted – all the more so because we stopped giving the aspirin after four years, yet the effect is continuing, and is directly correlated with the duration of aspirin use on the trial.”
Although scientists believe that diet is a major factor in the prevention of colorectal cancers, there are no randomized trial data which can prove it, since running proper, controlled trials of diet is extremely difficult. However, there is a strong inverse relationship between colon cancer and how much starch people eat. Resistant starch, after escaping digestion in the upper gut, is fermented in the colon and forms short chain fatty acids, which are powerful anti-cancer agents.
“Our very large colon probably evolved to capture such nutrients from our forefathers’ diets,” explained Prof Burn. “Because we were giving starch as well as aspirin we would also have expected to see a decrease in cancers in the placebo group. However, there could be a number of reasons for this result – perhaps patients didn’t take the starch every day, or that it simply wasn’t resistant enough.”
There were minor problems due to aspirin side effects; out of over 1000 people, 11 in the aspirin group had notable gastro-intestinal bleeds or ulcers as opposed to nine in the placebo group. But this was counter-balanced by fewer strokes and heart attacks in the aspirin group.
The mechanism by which aspirin protects against cancer has yet to be elucidated, but the scientists believe that cancer stem cells are involved. “We do not think that the mechanisms discussed to date are likely to provide an explanation,” said Prof Burn. “For example, the inflammatory enzyme COX2(Cyclooxygenase-2), a protein that acts as an enzyme and specifically catalyzes the production of certain chemical messengers called prostaglandins, is over-expressed in early cancer, but our results suggest an effect that predates the cancer, and may even predate the adenoma which precedes it. We believe that aspirin may have an effect on the survival of aberrant stem cells in the colon. These cancer stem cells are normally resistant to chemotherapy, but if a stem cell mutates but does not reveal its potential until an adenoma is formed, and if aspirin reduced the chances of such cells surviving, this would explain our results.”
The team intends to undertake a further study to see whether a smaller dose of aspirin would have the same beneficial effect or not. “We are planning to ask people with Lynch syndrome to agree to ‘toss a coin’ and take, say, either one or two aspirin tablets per day. Then we can see whether the people on the lower dose have the same protection, with fewer side effects. The problem is that, to have a significant result, this will need about 10 times as many people as we needed for our first trial, but the good news is that everyone gets treated,” said Prof Burn.
For more information:
- Abstract no: 6000, Gastro-intestinal malignancies, colorectal cancer session, Monday 11.00 hrs CEST (Hall 2)
Also read these PubMed abstracts:
- Hua A, Mackenzie GG, Rigas B. The differential cell signaling effects of two positional isomers of the anticancer NO-donating aspirin. Int J Oncol. 2009 Oct;35(4):837-44.
- Barry EL, Sansbury LB, Grau MV, Ali IU, Tsang S, et al. Cyclooxygenase-2 Polymorphisms, Aspirin Treatment, and Risk for Colorectal Adenoma Recurrence--Data from a Randomized Clinical Trial. Cancer Epidemiol Biomarkers Prev. 2009 Sep 15. [Epub ahead of print]
- Lang DL. Aspirin as Colorectal Cancer Adjuvant Therapy. Gastroenterology. 2009 Aug 22. [Epub ahead of print]
- Neugut AI. Aspirin as adjuvant therapy for colorectal cancer: a promising new twist for an old drug. JAMA. 2009 Aug 12;302(6):688-9
- Chan AT, Giovannucci EL, Meyerhardt JA, Schernhammer ES, et al. Aspirin dose and duration of use and risk of colorectal cancer in men. Gastroenterology. 2008 Jan;134(1):21-8. Epub 2007 Sep 26.
Wednesday, January 14, 2009
Waste from Olive Grinding May Inhibit Colorectal Cancer
Researchers from the University of Granada and the University of Barcelona have shown that treatment with maslinic acid, a triterpenoid compound isolated from olive-skin pomace, results in a significant inhibition of cell proliferation and causes apoptotic death in colorectal cancer cells.
Triterpenoids, which also includes maslinic or crataegolic acid, are compounds present in a wide range of plants used in traditional medicine and known to have anti-carcinogenic properties. Low concentrations of maslinic acid, a pentacyclic terpene, can be found in plants with medicinal properties. However, the compound is present in high concentrations in the leaf and the olive skin wax extracted from alpeorujo, the crushed olive waste from olive grinding, or dry olive-pomace oil.
Based on the results of the study, the researchers feel that the compound has the capacity to inhibit or prevent cancer as well as regulating apoptosis or programmed death in human HT29 colon adenocarcinoma cell lines via the intrinsic mitochondrial pathway. Scientifics now suggest that this mechanism of action could be a useful new therapeutic strategy for the treatment of colorectal cancer as it allows controlling the hyperplasia and hypertrophy processes.
A novel compound
This study is the first to investigate the precise molecular mechanisms of the anti-carcinogenic and pro-apoptotic effects of maslinic acid against colorectal cancer. Chemopreventive agents of a natural origin, often a part of our daily diet, may provide a cheap, effective way of controlling such diseases such as colorectal cancer. A wide range of European studies in recent years has shown that triterpenoids hinder carcinogenesis by intervening in pathways such as carcinogen activation, DNA repair, cell cycle arrest, cell differentiation and the induction of apoptosis in cancer cells.
Therapeutic use in HIV
In a number of previous but unrelated studies, researchers from the university of Granada have also shown that maslinic or crataegolic acid inhibits serine proteases or serine endopeptidases,
an enzyme used by HIV to release itself from the infected cell into the extracellular environment and, consequently, to spread the infection into the whole body. They determined that the use of maslinic acid can effective reduce, up to 80%, AIDS spreading in the body. Furthermore, maslinic acid is very active against opportunistic parasitic infections, including protozoa Cryptosporidium, a parasite commonly found in HIV-patients presenting with intestine infection and diarrhea.
The therapeutic effects of maslinic acid in the fight against AIDS are now simultaneously being studied by the researchers in Granada and by Professor Dr. Vallejo Nájera and his team at the Hospital Carlos III in Madrid, Spain.
Anti-inflammatory properties
While maslinic acid is only one of the compounds found in the leaf and the olive skin wax, researches have long observed the potential health and medical benefits of olive oil. Researchers from the Lipids and Atherosclerosis Unit at the Hospital Universitario Reina Sofía de Córdoba in Spain, carried out a study in order to determine the influence of the micronutrients of certain fats on cardiovascular diseases, diabetes or cancer. They also tried to discern if the consumption of these micronutrients could possibly modify the inflammatory process in healthy people.
Doctor Pablo Pérez Martínez, one of the researchers, studying these effects, said that ‘the main property of olive oil is its richness of antioxidants, which makes it a unique fat. Therefore, we must clarify which is the added value of its components, including maslinic acid, as that is the only way to establish that a healthy diet must contain olive oil as its main fat.’ Martínez believes that because ‘olive oil is… the main source of fats… in the Mediterranean diet, it provides [this diet] with high-nutritional-value micro-components.’ According to the researcher, such a diet reduces LDL-C, brings arterial pressure down, improves diabetes control and lessen effects from thrombosis.
For more information, read:
- Reyes-Zurita FJ, Rufino-Palomares EE, Lupiáñez JA, Cascante M. Maslinic acid, a natural triterpene from Olea europaea L., induces apoptosis in HT29 human colon-cancer cells via the mitochondrial apoptotic pathway. Cancer Lett. 2009 Jan 8;273(1):44-54. Epub 2008 Sep 14.
Also read PubMed abstracts:
- Parra A, Rivas F, Lopez PE, et al. Solution- and solid-phase synthesis and anti-HIV activity of maslinic acid derivatives containing amino acids and peptides. Bioorg Med Chem. 2008 Dec 25. [Epub ahead of print].
- Juan ME, Planas JM, Ruiz-Gutierrez V, et al. Antiproliferative and apoptosis-inducing effects of maslinic and oleanolic acids, two pentacyclic triterpenes from olives, on HT-29 colon cancer cells. Br J Nutr. 2008 Jul;100(1):36-43. Epub 2008 Feb 26.
- Juan ME, Wenzel U, Ruiz-Gutierrez V, Daniel H, Planas JM. Olive fruit extracts inhibit proliferation and induce apoptosis in HT-29 human colon cancer cells. J Nutr. 2006 Oct;136(10):2553-7. Contact the authors.
- Juan ME, Wenzel U, Daniel H, Planas JM. Erythrodiol, a natural triterpenoid from olives, has antiproliferative and apoptotic activity in HT-29 human adenocarcinoma cells. Mol Nutr Food Res. 2008 May;52(5):595-9. Contact the authors.
- Reyes FJ, Centelles JJ, Lupiáñez JA, Cascante M. (2Alpha,3beta)-2,3-dihydroxyolean-12-en-28-oic acid, a new natural triterpene from Olea europea, induces caspase dependent apoptosis selectively in colon adenocarcinoma cells. FEBS Lett. 2006 Nov 27;580(27):6302-10. Epub 2006 Oct 27.
- Gamet-Payrastre L, Li P, Lumeau S, Cassar G, et al. Sulforaphane, a Naturally Occurring Isothiocyanate, Induces Cell Cycle Arrest and Apoptosis in HT29 Human Colon Cancer. Cells. Cancer Res. 2000 Mar 1;60(5):1426-33.
Thursday, December 11, 2008
Preliminary Study Results Demonstrate that Zoledronic Acid May Have Anti-Tumor Properties
Early evaluations of zoledronic acid, a bisphosphonate used for the treatment of bone metastases in advanced breast cancer, suggest a possible direct anti-tumor effect when combined with neoadjuvant chemotherapy in breast cancer treatment, according to data presented at the CTRC-AACR San Antonio Breast Cancer Symposium. Bisphosphonates may therefore offer an (neo)adjuvant therapeutic strategy of potential importance.
“Zoledronic acid is primarily targeted to bone and metastasis within the bone marrow microenvironment, but it may also be enhancing the response in the primary breast tumor,” said Robert Coleman, M.D., FRCP, professor of medical oncology at the University of Sheffield in the United Kingdom. Coleman is the lead researcher on the AZURE (Adjuvant Zoledronic Acid to Reduce Recurrence) trial, which is evaluating the effect of zoledronic acid on breast cancer.
Although the larger AZURE trial is still being evaluated, if the findings in this smaller study are confirmed, the effect could be 'practice changing,' Coleman said. The AZURE trial, a prospective, randomized, open label, clinical trial , enrolled 3,360 women with stage II/III breast cancer to determine whether treatment with zoledronic acid in addition to adjuvant or neoadjuvant chemotherapy would improve disease outcomes. Coleman and colleagues performed a retrospective pathology analysis on 205 patients who received neoadjuvant chemotherapy to determine zoledronic acid’s impact on the primary tumor. Zoledronic acid appeared to reduce tumor size from 30 mm in the chemotherapy alone group to 20.5 mm in the combination group. After adjusting for variables like estrogen receptor status and treatment duration, the difference remained at 42.4 mm in the chemotherapy group and 28.2 mm in the combination group. The pathological complete response rate was 5.8% in the chemotherapy arm and 10.9% in the zoledronic acid group.
The number of patients requiring mastectomy was 77.9% in the chemotherapy group and 65.3% in the combination group. “Zoledronic acid is currently approved for the treatment of bone metastasis and osteoporosis. If the AZURE trial remains positive, then we’ll file for an additional indication,” said Coleman.
For more information
“Zoledronic acid is primarily targeted to bone and metastasis within the bone marrow microenvironment, but it may also be enhancing the response in the primary breast tumor,” said Robert Coleman, M.D., FRCP, professor of medical oncology at the University of Sheffield in the United Kingdom. Coleman is the lead researcher on the AZURE (Adjuvant Zoledronic Acid to Reduce Recurrence) trial, which is evaluating the effect of zoledronic acid on breast cancer.
Although the larger AZURE trial is still being evaluated, if the findings in this smaller study are confirmed, the effect could be 'practice changing,' Coleman said. The AZURE trial, a prospective, randomized, open label, clinical trial , enrolled 3,360 women with stage II/III breast cancer to determine whether treatment with zoledronic acid in addition to adjuvant or neoadjuvant chemotherapy would improve disease outcomes. Coleman and colleagues performed a retrospective pathology analysis on 205 patients who received neoadjuvant chemotherapy to determine zoledronic acid’s impact on the primary tumor. Zoledronic acid appeared to reduce tumor size from 30 mm in the chemotherapy alone group to 20.5 mm in the combination group. After adjusting for variables like estrogen receptor status and treatment duration, the difference remained at 42.4 mm in the chemotherapy group and 28.2 mm in the combination group. The pathological complete response rate was 5.8% in the chemotherapy arm and 10.9% in the zoledronic acid group.
The number of patients requiring mastectomy was 77.9% in the chemotherapy group and 65.3% in the combination group. “Zoledronic acid is currently approved for the treatment of bone metastasis and osteoporosis. If the AZURE trial remains positive, then we’ll file for an additional indication,” said Coleman.
For more information
- Winter MC, Thorpe HC, Burkinshaw R, Beevers SJ, Coleman RE, The addition of zoledronic acid to neoadjuvant chemotherapy may influence pathological response exploratory evidence for direct anti-tumor activity in breast cancer. Abstract 5101; SABCS, December 10-14, 2008.
Monday, December 8, 2008
Patients may benefit from new therapeutic approaches in several platelet disorders
A new combination therapy for previously untreated idiopathic thrombocytopenic purpura (ITP), an investigational oral treatment for chronic ITP, a low-dose platelet transfusion strategy for patients with hypoproliferative thrombocytopenia, and a new therapeutic platelet transfusion approach following high-dose chemotherapy and autologous stem cell transplantation, may benefit patients with various forms of thrombocytopenia.
Thrombocytopenia is a group of bleeding disorders characterized by a low number of platelets in the blood. Failed platelet production, increased splenic sequestration of platelets with normal platelet survival, increased platelet destruction or consumption, dilution of platelets, or a combination of these are the main causes of this condition.
Four studies presented during the during the 50th Annual Meeting of the American Society of Hematology in San Francisco, CA (December 6 - 9) on Saturday, highlighted significant advances in treatment and survival outcomes for patients with various forms of thrombocytopenia.
“We have some very exciting data on novel therapeutic approaches to minimize bleeding episodes in patients with platelet disorders,” explained Kenneth Kaushansky, MD, 2008 President of the American Society of Hematology and Helen M. Ranney Professor and Chair of the Department of Medicine at the University of California, San Diego School of Medicine. “The results of these studies will likely transform the way hematologists treat and manage these conditions, ultimately resulting in improvements in overall patient outcomes such as reducing bruising and unnecessary bleeding that can result if left untreated.”
Types of thrombocytopenia, a blood disorder with 50 to 150 new cases per 1 million people each year, are typically classified by one of three causes: low production of platelets in the bone marrow, increased breakdown of platelets in the bloodstream, or increased breakdown of platelets in the spleen or liver, which can be induced by certain anemias, cancers, infections, or medications. Symptoms can include bruising, nose bleeds, bleeding in the mouth, and rash-like spots on the skin.
If left untreated, thrombocytopenia can become a life-threatening condition when blood platelet counts fall below 5,000 microliters because the risk of serious hemorrhaging or (excessive bleeding) increases. Normal blood platelet counts are typically between 150,000 to 450,000 microliters in adults. Treatment for thrombocytopenia is dependent on the cause and severity of the condition and can include drug therapy, splenectomy (the spleen breaks down blood cells such as platelets), and platelet transfusions.
Rituximab and Dexamethasone vs Dexamethasone Alone in Idiopathic thrombocytopenic purpura
Results from a multicenter phase III study conducted by a team of researchers from Clinica Ematologica DIRM AOUD, Udine, Italy, were presented by Francesco Zaja, MD.
This study is the first trial to prospectively determine that adding the immunotherapy drug rituximab, an anti-CD20 monoclonal antibody, to dexamethasone, a steroid that is a standard therapy for idiopathic thrombocytopenic purpura (ITP), is safe and effective in adult patients with previously untreated ITP, an autoimmune disorder characterized by low platelet counts. Primary ITP, which typically occurs in an otherwise healthy individuals, has an unknown etiology.
After analyzing the data, the researchers concluded that this treatment regimen could be an effective option prior to splenectomy for some patients as well as a possible cure for others.
In this study, patients were randomized to one of two treatment regimens: oral dexamethasone alone (40 mg) given on the first four days of treatment or the same regimen of dexamethasone plus rituximab given as an intravenous infusion (375 mg/m2) once a week for four weeks. Some patients in the dexamethasone-only arm who failed to achieve a sustained response and had platelet counts of less than or equal to 20 x 109/L following 30 days of therapy up to the end of six months received a salvage (rescue) treatment of rituximab plus dexamethasone.
The primary objective of the study was to compare the sustained response (platelet counts greater than or equal to 50 x 109/L from one month to six months from the beginning of therapy) between the two treatment groups. Secondary objectives included overall safety, initial response (platelet count of 50 x 109/L after 30 days of treatment), activity of the salvage therapy (dexamethasone/rituximab) in patients not responding to dexamethasone alone, the identification of clinical and laboratory factors predictive of response, and the pharmacokinetic parameters of rituximab (the level of ritixumab circulating in the blood of patients during the study period) and their potential relation to response.
The researchers examined the results for all enrolled patients, regardless of whether or not they completed the study (intention-to-treat basis, ITT), and on a per-protocol (PP) basis, examining those who had completed the treatment regimen. The ITT group included 52 patients treated with dexamethasone alone and 49 treated with rituximab/dexamethasone. The PP group included 38 patients treated with dexamethasone alone and 26 treated with rituximab/dexamethasone. ITT and PP sustained response rates were 63 percent and 85 percent in the rituximab/dexamethasone combination arm as compared with 36 percent and 39 percent in the dexamethasone-alone arm.
A total of 27 patients who failed to achieve an initial or sustained response in the dexamethasone-alone arm received the salvage treatment. In this group, ITT and PP sustained response rates were 56 percent and 59 percent, respectively.
While were no clinical or laboratory factors predictive of a sustained response identified in the study, the researchers did report a mild increase in the incidence of severe adverse events in the dexamethasone-plus-rituximab arm (2 percent in dexamethasone arm versus 6 percent in dexamethasone-plus-rituximab arm).
For more infromation, read:
Francesco Zaja, Michele Baccarani, Patrizio Mazza, Nicola Vianelli, et al. A Prospective Randomized Study Comparing Rituximab and Dexamethasone Vs Dexamethasone Alone in ITP: Results of Final Analysis and Long Term Follow up. (Plenary Session), Blood (ASH Annual Meeting Abstracts) 2008 112: Abstract #1
Click here for an educational resource (The ITP Paradox).
Also read Pubmed abstracts:
Effects of Prophylactic Platelet Dose on Transfusion Outcomes (PLADO Trial)
Patients with hypoproliferative thrombocytopenia can be safely and effectively transfused with a low dose of platelets, a strategy that can reduce costs and help prevent shortages in the blood supply. This is the conclusion of Sherrill J. Slichter, MD and her team of researchers at Puget Sound Blood Center for the National Heart, Lung, and Blood Institute Transfusion Medicine/Hemostasis Clinical Trials Network, Seattle, WA, analyzing the data of the first large-scale clinical trial comparing the effects of different platelet-transfusion dosing regimens on hemostatic outcomes.
A total of 1,272 patients with hypoproliferative thrombocytopenia, which is caused by failure of the marrow to produce platelets, who were expected to be hospitalized with platelet counts of less than or equal to 10,000 microliters for more than five days were enrolled in the study and received at least one platelet transfusion. Patients were randomized to receive one of three platelet-transfusion dosing regimens: a low dose (1.1 x 1011 platelets/m2), a medium dose (2.2 x 1011 platelets/m2), or a high dose (4.4 x 1011 platelets/m2). An acceptable dose of platelets could be within 25 percent (lower or higher) of the target dose.
Participating patients were stratified into four groups based on the cause of thrombocytopenia: those who had received chemotherapy for a hematologic malignancy (313 patients), chemotherapy for a solid tumor (seven patients), autologous stem cell transplant (429 patients), or an allogeneic stem cell transplant (523 patients). Patients were prophylactically transfused on days when platelet counts were less than or equal to 10,000 microliters.
The primary endpoint of the study was the percentage of patients with Grade 2 or higher bleeding, calculated using the WHO Bleeding Scale. Grade 2 bleeding is clinically significant bleeding that does not require a red blood cell transfusion. Grade 2 or higher bleeding occurred in 71 percent of patients in the low-dose arm, 69 percent in the medium-dose arm, and 70 percent in the high-dose arm. Grade 3 or higher bleeding, which generally does require treatment by red blood cell transfusion, was seen in 12 percent of patients in the low-dose arm, 9 percent in the medium-dose arm, and 10 percent in the high-dose arm. Grade 4 bleeding, the most serious, was seen in 3 percent, 2 percent, and 2 percent of patients in the low-dose, medium-dose, and high-dose arms, respectively. The median number of red blood cell transfusions (usually given for anemia) was four in each treatment arm. Treatment dose did not affect the frequency of any bleeding grade in any of the four patient groups.
For more information, please read:
Sherrill J. Slichter, MD, Richard M. Kaufman, MD, Susan F Assmann, PhD, Mark E. Brecher, MD, BC. Effects of Prophylactic Platelet (Plt) Dose on Transfusion (Tx) Outcomes (PLADO Trial) Blood (ASH Annual Meeting Abstracts) 2008 112: Abstract #285
Also read PubMed abstracts:
Patients who received eltrombopag were eight times more likely to achieve platelet counts of 50,000 to 400,000 microliters during the six-month treatment period as compared with those in the placebo arm. While baseline median platelet counts were 16,000 microliters in both groups, platelet counts never exceeded 30,000 microliters in the placebo group. This is in contrast to median platelet counts rising to 36,000 microliters in the eltrombopag group after one week of treatment and ranging from 52,000 to 91,000 microliters for the remainder of the study. Median platelet counts returned to baseline levels two weeks after stopping eltrombopag.
Significantly fewer patients treated with eltrombopag experienced any bleeding or clinically significant bleeding throughout the study as compared with those in the placebo arm. Additionally, more patients in the eltrombopag arm were able to stop or reduce other ITP medication and required less rescue therapy compared with those in the placebo group. Overall incidence of adverse events was similar in both treatment groups and was mostly mild to moderate.
More information, please read:
Gregory Cheng, Mansoor N Saleh, James B Bussel, Claus Marcher. Oral Eltrombopag for the Long-Term Treatment of Patients with Chronic Idiopathic Thrombocytopenic Purpura: Results of a Phase III, Double- Blind, Placebo-Controlled Study (RAISE). Blood (ASH Annual Meeting Abstracts) 2008 112: Abstract #400
Also read PubMed abstracts:
Also read NEJM article (full article):
McHutchison JG, Dusheiko G, Shiffman ML, Rodriguez-Torres M. Eltrombopag for Thrombocytopenia in Patients with Cirrhosis Associated with Hepatitis C. N Engl J Med. 2007 Nov 29;357(22):2227-36. Clieck here for the PubMed abstract. Author reply.
Thrombocytopenia is a group of bleeding disorders characterized by a low number of platelets in the blood. Failed platelet production, increased splenic sequestration of platelets with normal platelet survival, increased platelet destruction or consumption, dilution of platelets, or a combination of these are the main causes of this condition.
Four studies presented during the during the 50th Annual Meeting of the American Society of Hematology in San Francisco, CA (December 6 - 9) on Saturday, highlighted significant advances in treatment and survival outcomes for patients with various forms of thrombocytopenia.
“We have some very exciting data on novel therapeutic approaches to minimize bleeding episodes in patients with platelet disorders,” explained Kenneth Kaushansky, MD, 2008 President of the American Society of Hematology and Helen M. Ranney Professor and Chair of the Department of Medicine at the University of California, San Diego School of Medicine. “The results of these studies will likely transform the way hematologists treat and manage these conditions, ultimately resulting in improvements in overall patient outcomes such as reducing bruising and unnecessary bleeding that can result if left untreated.”
Types of thrombocytopenia, a blood disorder with 50 to 150 new cases per 1 million people each year, are typically classified by one of three causes: low production of platelets in the bone marrow, increased breakdown of platelets in the bloodstream, or increased breakdown of platelets in the spleen or liver, which can be induced by certain anemias, cancers, infections, or medications. Symptoms can include bruising, nose bleeds, bleeding in the mouth, and rash-like spots on the skin.
If left untreated, thrombocytopenia can become a life-threatening condition when blood platelet counts fall below 5,000 microliters because the risk of serious hemorrhaging or (excessive bleeding) increases. Normal blood platelet counts are typically between 150,000 to 450,000 microliters in adults. Treatment for thrombocytopenia is dependent on the cause and severity of the condition and can include drug therapy, splenectomy (the spleen breaks down blood cells such as platelets), and platelet transfusions.
Rituximab and Dexamethasone vs Dexamethasone Alone in Idiopathic thrombocytopenic purpura
Results from a multicenter phase III study conducted by a team of researchers from Clinica Ematologica DIRM AOUD, Udine, Italy, were presented by Francesco Zaja, MD.
This study is the first trial to prospectively determine that adding the immunotherapy drug rituximab, an anti-CD20 monoclonal antibody, to dexamethasone, a steroid that is a standard therapy for idiopathic thrombocytopenic purpura (ITP), is safe and effective in adult patients with previously untreated ITP, an autoimmune disorder characterized by low platelet counts. Primary ITP, which typically occurs in an otherwise healthy individuals, has an unknown etiology.
After analyzing the data, the researchers concluded that this treatment regimen could be an effective option prior to splenectomy for some patients as well as a possible cure for others.
In this study, patients were randomized to one of two treatment regimens: oral dexamethasone alone (40 mg) given on the first four days of treatment or the same regimen of dexamethasone plus rituximab given as an intravenous infusion (375 mg/m2) once a week for four weeks. Some patients in the dexamethasone-only arm who failed to achieve a sustained response and had platelet counts of less than or equal to 20 x 109/L following 30 days of therapy up to the end of six months received a salvage (rescue) treatment of rituximab plus dexamethasone.
The primary objective of the study was to compare the sustained response (platelet counts greater than or equal to 50 x 109/L from one month to six months from the beginning of therapy) between the two treatment groups. Secondary objectives included overall safety, initial response (platelet count of 50 x 109/L after 30 days of treatment), activity of the salvage therapy (dexamethasone/rituximab) in patients not responding to dexamethasone alone, the identification of clinical and laboratory factors predictive of response, and the pharmacokinetic parameters of rituximab (the level of ritixumab circulating in the blood of patients during the study period) and their potential relation to response.
The researchers examined the results for all enrolled patients, regardless of whether or not they completed the study (intention-to-treat basis, ITT), and on a per-protocol (PP) basis, examining those who had completed the treatment regimen. The ITT group included 52 patients treated with dexamethasone alone and 49 treated with rituximab/dexamethasone. The PP group included 38 patients treated with dexamethasone alone and 26 treated with rituximab/dexamethasone. ITT and PP sustained response rates were 63 percent and 85 percent in the rituximab/dexamethasone combination arm as compared with 36 percent and 39 percent in the dexamethasone-alone arm.
A total of 27 patients who failed to achieve an initial or sustained response in the dexamethasone-alone arm received the salvage treatment. In this group, ITT and PP sustained response rates were 56 percent and 59 percent, respectively.
While were no clinical or laboratory factors predictive of a sustained response identified in the study, the researchers did report a mild increase in the incidence of severe adverse events in the dexamethasone-plus-rituximab arm (2 percent in dexamethasone arm versus 6 percent in dexamethasone-plus-rituximab arm).
For more infromation, read:
Francesco Zaja, Michele Baccarani, Patrizio Mazza, Nicola Vianelli, et al. A Prospective Randomized Study Comparing Rituximab and Dexamethasone Vs Dexamethasone Alone in ITP: Results of Final Analysis and Long Term Follow up. (Plenary Session), Blood (ASH Annual Meeting Abstracts) 2008 112: Abstract #1
Click here for an educational resource (The ITP Paradox).
Also read Pubmed abstracts:
- Medeot M, Zaja F, Vianelli N, Battista M, et al. Rituximab therapy in adult patients with relapsed or refractory immune thrombocytopenic purpura: long-term follow-up results. Eur J Haematol. 2008 Sep;81(3):165-9. Epub 2008 May 27.
- Toffoletti E, Zaja F, Chiarvesio A, Michelutti A, et al. No evidences for B-cell clonality by spectratyping analysis in patients with idiopathic thrombocytopenic purpura undergoing rituximab therapy. Haematologica. 2008 May;93(5):795-6.
- Stasi R, Cooper N, Del Poeta G, Stipa E, et al. Analysis of regulatory T-cell changes in patients with idiopathic thrombocytopenic purpura receiving B cell-depleting therapy with rituximab. Blood. 2008 Aug 15;112(4):1147-50. Epub 2008 Mar 28.
Effects of Prophylactic Platelet Dose on Transfusion Outcomes (PLADO Trial)
Patients with hypoproliferative thrombocytopenia can be safely and effectively transfused with a low dose of platelets, a strategy that can reduce costs and help prevent shortages in the blood supply. This is the conclusion of Sherrill J. Slichter, MD and her team of researchers at Puget Sound Blood Center for the National Heart, Lung, and Blood Institute Transfusion Medicine/Hemostasis Clinical Trials Network, Seattle, WA, analyzing the data of the first large-scale clinical trial comparing the effects of different platelet-transfusion dosing regimens on hemostatic outcomes.
A total of 1,272 patients with hypoproliferative thrombocytopenia, which is caused by failure of the marrow to produce platelets, who were expected to be hospitalized with platelet counts of less than or equal to 10,000 microliters for more than five days were enrolled in the study and received at least one platelet transfusion. Patients were randomized to receive one of three platelet-transfusion dosing regimens: a low dose (1.1 x 1011 platelets/m2), a medium dose (2.2 x 1011 platelets/m2), or a high dose (4.4 x 1011 platelets/m2). An acceptable dose of platelets could be within 25 percent (lower or higher) of the target dose.
Participating patients were stratified into four groups based on the cause of thrombocytopenia: those who had received chemotherapy for a hematologic malignancy (313 patients), chemotherapy for a solid tumor (seven patients), autologous stem cell transplant (429 patients), or an allogeneic stem cell transplant (523 patients). Patients were prophylactically transfused on days when platelet counts were less than or equal to 10,000 microliters.
The primary endpoint of the study was the percentage of patients with Grade 2 or higher bleeding, calculated using the WHO Bleeding Scale. Grade 2 bleeding is clinically significant bleeding that does not require a red blood cell transfusion. Grade 2 or higher bleeding occurred in 71 percent of patients in the low-dose arm, 69 percent in the medium-dose arm, and 70 percent in the high-dose arm. Grade 3 or higher bleeding, which generally does require treatment by red blood cell transfusion, was seen in 12 percent of patients in the low-dose arm, 9 percent in the medium-dose arm, and 10 percent in the high-dose arm. Grade 4 bleeding, the most serious, was seen in 3 percent, 2 percent, and 2 percent of patients in the low-dose, medium-dose, and high-dose arms, respectively. The median number of red blood cell transfusions (usually given for anemia) was four in each treatment arm. Treatment dose did not affect the frequency of any bleeding grade in any of the four patient groups.
For more information, please read:
Sherrill J. Slichter, MD, Richard M. Kaufman, MD, Susan F Assmann, PhD, Mark E. Brecher, MD, BC. Effects of Prophylactic Platelet (Plt) Dose on Transfusion (Tx) Outcomes (PLADO Trial) Blood (ASH Annual Meeting Abstracts) 2008 112: Abstract #285
Also read PubMed abstracts:
- Slichter SJ, Evidence-based platelet transfusion guidelines. Hematology Am Soc Hematol Educ Program. 2007;2007:172-8.
- Slichter SJ, Platelet transfusion therapy. Hematol Oncol Clin North Am. 2007 Aug;21(4):697-729, vii.
Therapeutic platelet transfusion without prophylactic transfusion may significantly reduces platelet transfusion needs.
This study is the first worldwide randomized trial showing that one-quarter to one-third of all platelet transfusions were given unnecessarily in the past and can be reduced in the future without any harm to patients following high-dose chemotherapy and autologous stem cell transplantation, according to Dr. Wandt. MD, at the Klinikum Nuremberg Nord, Nuremberg, Germany.
In this multicenter, randomized trial, the researchers found that the development of major bleeding following high-dose chemotherapy and autologous stem cell transplant can be prevented through an experimental therapeutic strategy in which patients receive platelet transfusions only if they have experienced clinically relevant bleeding. The experimental strategy in this trial was compared with a traditional preventive transfusion strategy in which patients received a transfusion if platelet counts were less than or equal to 10/nL. The researchers concluded that the experimental strategy was both cost effective and safe in this patient population.
A total of 171 patients who had recently received high-dose chemotherapy or autologous stem cell transplant for the treatment of various hematologic cancers, including multiple myeloma, non-Hodgkin lymphoma, Hodgkin disease, and acute leukemia, were randomized to one of two treatment arms: a traditional arm that received preventive platelet transfusions or an experimental arm that was treated only if the patient had experienced signs of clinically relevant bleeding. The primary objective of the study was the reduction of platelet transfusions by 15 to 25 percent. Secondary objectives included safety, duration of leukopenia and thrombocytopenia, and the number of red blood cell transfusions.
Platelet transfusions were significantly reduced by 27 percent in the experimental arm as compared with the traditional arm. In the experimental arm, 46 percent of patients did not need any platelet transfusions, compared with 22 percent of patients in the traditional arm. Using clinically relevant bleeding as the trigger for platelet transfusions rather than using platelet counts of less than or equal to 10/nL as the trigger resulted in more minor hemorrhages occurring in the experimental arm as compared with the traditional arm (28.7 percent versus 9.5 percent); however, no life-threatening or fatal bleeding was reported. The duration of leukopenia and the need for red blood cell transfusions were the same in both arms.
For more information, please read:
Hannes Wandt, MD, Knut Wendelin, MD, Kerstin Schaefer-Eckart, MD, Markus Thalheimer, MD. A Therapeutic Platelet Transfusion Strategy without Routine Prophylactic Transfusion Is Feasible and Safe and Reduces Platelet Transfusion Numbers Significantly: Preliminary Analysis of a Randomized Study in Patients after High Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation. Blood (ASH Annual Meeting Abstracts) 2008 112: Abstract #286.
Also read PubMed abstracts:
Wandt H, Schaefer-Eckart K, Frank M. et al. A therapeutic platelet transfusion strategy is safe and feasible in patients after autologous peripheral blood stem cell transplantation. Bone Marrow Transplant. 2006 Feb;37(4):387-92.
Oral Eltrombopag for the treatment of chronic Idiopathic Thrombocytopenic Purpura (ITP)
This double-blind, multicenter, phase III study found that long-term therapy with eltrombopag, a thrombopoietin-receptor agonist, compared with placebo treatment significantly increased platelet counts, decreased bleeding symptoms, allowed for a reduction of baseline ITP therapy, and reduced the use of rescue medications in previously treated patients with chronic ITP. In chronic ITP, low blood platelet counts persist unless treated and can last for an indefinite amount of time.
In this study Gregory Cheng, MD and his team of researchers at the Chinese University of Hong Kong, Hong Kong, China, stratified 197 patients with platelet counts less than 30,000 microliters by splenectomy status, use of baseline ITP medication, and platelets of less than or equal to 15,000 microliters. Patients were randomized to receive either eltrombopag at a starting dose of 50 mg once daily (135 patients) or placebo once daily (62 patients).
Depending on individual platelet response, the dose of eltrombopag could be titrated within a range from 25 mg once daily to a maximum dose of 75 mg once daily. The primary endpoint of the study was the odds of achieving platelet counts between 50,000 and 400,000 microliters in patients receiving eltrombopag as compared with placebo. To measure the drug’s safety, bleeding symptoms were prospectively evaluated using the WHO Bleeding Scale.Patients who received eltrombopag were eight times more likely to achieve platelet counts of 50,000 to 400,000 microliters during the six-month treatment period as compared with those in the placebo arm. While baseline median platelet counts were 16,000 microliters in both groups, platelet counts never exceeded 30,000 microliters in the placebo group. This is in contrast to median platelet counts rising to 36,000 microliters in the eltrombopag group after one week of treatment and ranging from 52,000 to 91,000 microliters for the remainder of the study. Median platelet counts returned to baseline levels two weeks after stopping eltrombopag.
Significantly fewer patients treated with eltrombopag experienced any bleeding or clinically significant bleeding throughout the study as compared with those in the placebo arm. Additionally, more patients in the eltrombopag arm were able to stop or reduce other ITP medication and required less rescue therapy compared with those in the placebo group. Overall incidence of adverse events was similar in both treatment groups and was mostly mild to moderate.
More information, please read:
Gregory Cheng, Mansoor N Saleh, James B Bussel, Claus Marcher. Oral Eltrombopag for the Long-Term Treatment of Patients with Chronic Idiopathic Thrombocytopenic Purpura: Results of a Phase III, Double- Blind, Placebo-Controlled Study (RAISE). Blood (ASH Annual Meeting Abstracts) 2008 112: Abstract #400
Also read PubMed abstracts:
- Stasi R. Evangelista ML, Amadori S. Novel thrombopoietic agents: a review of their use in idiopathic thrombocytopenic purpura. Drugs. 2008;68(7):901-12
- Lawson, A. Eltrombopag in thrombocytopenia. N Engl J Med. Mar 6;358(10):1072; author reply 1072-3
- Newland A. Emerging strategies to treat chronic immune thrombocytopenic purpura. Eur J Haematol Suppl. 2008 Feb;(69):27-33.
Also read NEJM article (full article):
McHutchison JG, Dusheiko G, Shiffman ML, Rodriguez-Torres M. Eltrombopag for Thrombocytopenia in Patients with Cirrhosis Associated with Hepatitis C. N Engl J Med. 2007 Nov 29;357(22):2227-36. Clieck here for the PubMed abstract. Author reply.
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