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
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Showing posts with label oncology. Show all posts
Showing posts with label oncology. Show all posts
Thursday, November 25, 2010
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:
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
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]
Saturday, December 12, 2009
Small, HER2-Positive, Tumors Linked with Poor Prognosis
Patients with breast cancer whose tumors were HER2-positive and one centimeter or smaller had a significant risk of relapse compared with other tumor types, according to a new study presented at the CRTC-AACR San Antonio Breast Cancer Symposium.
“The current guidelines call for no further therapy if the tumors are less than five millimeters or consider therapy if the tumors are from six to 10 millimeters, but this data challenges that thinking and shows this group of women may benefit from additional therapy,” said Ana M. Gonzalez-Angulo, M.D., assistant professor in the Departments of Breast Medical Oncology and Systems Biology at the University of Texas M. D. Anderson Cancer Center (MDACC).
Gonzalez-Angulo and Ronjay Rakkhit, chief fellow of Hematology-Oncology at M. D. Anderson, and colleagues retrospectively studied 965 patients from MDACC and validated their findings with 350 patients from two European institutions. Patients with a lack of receptor information, and/or who had received adjuvant chemotherapy or trastuzumab at any time were excluded.
“This is the largest study of its kind in a patient population, and as our ability to detect tumors improves, this patient population will only continue to increase. Further, it answers a common question oncologist have in daily practice – which early stage patients may be in need of additional therapy,” said AMG. Patients were diagnosed between 1990 and 2003. Median age of the patients at diagnosis was 57 years. All tumors were one centimeter or smaller. Most of the tumors (68%) were hormone receptor-positive, while 10 percent were HER2-positive and 23% were triple receptor-negative.
Five-year, recurrence-free survival was 77.1% 93.7% in patients with HER2-positive and HER2-negative tumors, respectively, and five-year distant recurrence-free survival was 86.4% and 97.2%, in patients with HER2-positive and HER2-negative tumors, respectively. Patients with HER2-positive tumors had 2.68 times greater risk of recurrence and 5.3 times higher the risk of distant recurrence than those with HER2-negative tumors.
Patients with HER2-positive tumors had 5.09 times the risk of recurrence and 7.81 times the risk of distant recurrence compared to patients with hormone receptor-positive tumors.
Data on 350 additional patients treated at two other institutions showed reproducibility, said Gonzalez. “This paper shows that patients with HER2-positive tumors one centimeter or less have a significant risk of relapse and should be considered for clinical trials of systemic anti-HER2 adjuvant therapy, or if a clinical trial is not available, adjuvant therapy should be discussed with them”, said Gonzalez-Angulo.
“The current guidelines call for no further therapy if the tumors are less than five millimeters or consider therapy if the tumors are from six to 10 millimeters, but this data challenges that thinking and shows this group of women may benefit from additional therapy,” said Ana M. Gonzalez-Angulo, M.D., assistant professor in the Departments of Breast Medical Oncology and Systems Biology at the University of Texas M. D. Anderson Cancer Center (MDACC).
Gonzalez-Angulo and Ronjay Rakkhit, chief fellow of Hematology-Oncology at M. D. Anderson, and colleagues retrospectively studied 965 patients from MDACC and validated their findings with 350 patients from two European institutions. Patients with a lack of receptor information, and/or who had received adjuvant chemotherapy or trastuzumab at any time were excluded.
“This is the largest study of its kind in a patient population, and as our ability to detect tumors improves, this patient population will only continue to increase. Further, it answers a common question oncologist have in daily practice – which early stage patients may be in need of additional therapy,” said AMG. Patients were diagnosed between 1990 and 2003. Median age of the patients at diagnosis was 57 years. All tumors were one centimeter or smaller. Most of the tumors (68%) were hormone receptor-positive, while 10 percent were HER2-positive and 23% were triple receptor-negative.
Five-year, recurrence-free survival was 77.1% 93.7% in patients with HER2-positive and HER2-negative tumors, respectively, and five-year distant recurrence-free survival was 86.4% and 97.2%, in patients with HER2-positive and HER2-negative tumors, respectively. Patients with HER2-positive tumors had 2.68 times greater risk of recurrence and 5.3 times higher the risk of distant recurrence than those with HER2-negative tumors.
Patients with HER2-positive tumors had 5.09 times the risk of recurrence and 7.81 times the risk of distant recurrence compared to patients with hormone receptor-positive tumors.
Data on 350 additional patients treated at two other institutions showed reproducibility, said Gonzalez. “This paper shows that patients with HER2-positive tumors one centimeter or less have a significant risk of relapse and should be considered for clinical trials of systemic anti-HER2 adjuvant therapy, or if a clinical trial is not available, adjuvant therapy should be discussed with them”, said Gonzalez-Angulo.
Saturday, October 3, 2009
New Drug May Offer Hope for Adrenocortical Carcinoma Patients
TGen Clinical Research Services (TCRS) at Scottsdale Healthcare in Scottsdale, Arizona, recently announced the start of a clinical trial for a drug designed to combat adrenocortical carcinoma (ACC), a rare but deadly cancer that forms in the cortex (steroid hormone-producing tissue) of the adrenal glands, a small organ on top of each kidney that makes steroid hormones, adrenaline, and noradrenaline.
The adrenal glands are responsible for making several critical hormones, including cortisol, which the body needs in order to respond to stress and which helps to maintain normal blood sugar levels in children.
Adrenal carcinoma (ACC) affects 1 to 2 per million population annually and may be curable if treated at an early stage. Radical surgical excision is the treatment of choice for localized malignancies and remains the only method by which long-term disease-free survival may be achieved. Overall 5-year survival for tumors resected for cure is approximately 40%. Retrospective studies have identified two important prognostic factors: completeness of resection and stage of disease. The most common sites of metastases are the peritoneum, lung, liver, and bone.
Other than surgery, the only treatment for ACC is the exacting use of a compound called mitotane (Lysodren®, Bristol-Myers Squibb), a chemical relative of DDT, which the U.S. banned as an insecticide in 1972, systemic chemotherapy, or (for localized lesions) radiation therapy.
While use of mitotane in ACC patients reduces tumors, it also diminishes adrenal gland function, requiring patients to take hormone replacements for the rest of their lives. In addition, mitotane must be administered for at least three months in order to reach a therapeutic level. Even then, it has proved effective in about 22% of ACC cases. When given with other chemotherapy drugs, the effectiveness of mitotane may be improved, but patients often suffer debilitating side effects.
Clinicians at TGen Clinical Research Services (TCRS), a strategic alliance between the Translational Genomics Research Institute (TGen) and Scottsdale Healthcare, hope that a new compound, OSI-906, a small molecule IGF-1R inhibitor that blocks the chemical pathway that otherwise allows the ACC tumors to grow out of control.
The drug candidate is developed by OSI Pharmaceuticals Inc. of Melville, N.Y., and will stop ACC tumor growth — perhaps even promote tumor shrinkage — without the toxic side effects of current chemotherapies. The trial will focus on patients with inoperable tumors who have relapsed or failed to respond to conventional therapies.
IGF-1R inhibitor
OSI-906 is a potent, selective orally active inhibitor of the insulin-like growth factor-1 receptor (IGF-1R) which has been viewed as an important therapeutic target due to its involvement in the growth and proliferation in a variety of human cancers, including adrenocortical carcinoma (ACC), ovarian and non-small cell lung cancers.
The new drug candidate stimulates proliferation, enables onogenic transformation, and suppresses apoptosis. Inhibitors of IGF-1R are expected to have broad utility in oncology since the over-expression of IGF-1R and/or its ligands or the down-regulation of ligand binding proteins occurs in numerous human malignancies including lung, colon, breast, prostate, brain and skin cancers. In addition, signaling through the IGF system has been implicated in protecting tumor cells from apoptosis induced by anti-cancer treatments such as cytotoxic agents and EGFR inhibitors. Scientists therefore believe that OSI-906 may be useful both as a single agent and in combination with other targeted therapies such as erlotinib (Tarceva® marketed by Genentech Bioncology and OSI Pharmaceuticals).
Ongoing research
During the 2009 annual meeting of ASCO, the American Society of Clinical Oncology, a number of abstracts were published with IGF-1R inhibitors in a range of cancers, making a case for insulin growth factor receptor (IGF-1R) inhibitors as a potential target for cancer therapeutics. So far, the data presented at ASCO has been very preliminary and isolated responses were seen.
In addition to OSI (OSI-906), a number of pharmaceutical and research companies have active, ongoing research programs in the clinic. Many other companies are involved in preliminary research in different stages in different cancers (Exelixis/XL228, Amgen/AMG-479, Roche/R1507, Pfizer/CP-751,871/Figitumumab, BMS/BMS-754807, Merck/MK-0646, and Imclone/Lilly/IMC A12). Others companies, including Sanofi-Aventis, Novartis, Eisai, Biogen Idec, are interested to see how this new class pans out.
OSI-906 trial
A clinical trial of OSI-906 is expected to last several years and include 135 patients, with 30-40 enrolled at TCRS. As there is no standard therapy available, two-thirds of the patients will receive the drug OSI-906 while one-third receives a placebo. Sites elsewhere in the U.S., as well as in Europe and Australia, are expected to enroll patients over the coming months.
“The trial is major step toward helping patients with ACC, who often face radical surgery as part of their treatment,” said Dr. Michael J. Demeure, who will oversee the trial locally. Dr. Demeure is a TGen Senior Investigator and a Scottsdale Healthcare surgeon experienced in removing ACC tumors.
“It’s a big operation requiring a large incision because these tumors can be the size of a football. Unfortunately many patients’ tumors have spread so we can’t remove it all, so new treatments are needed.’’ Demeure explained. “This unique partnership between Scottsdale Healthcare and TGen allows us to bring the newest and most promising treatments to patients with cancer right here in Arizona.”
The TCRS clinic in the Virginia G. Piper Cancer Center at Scottsdale Healthcare Shea is the first site worldwide approved for these clinical trials.
"Being the first site in the world for clinical trials of this drug adds to the long list of ‘firsts’ for the Virginia G. Piper Cancer Center,” said Mark Slater, Ph.D., vice president of research. "Scottsdale Healthcare’s collaborations with world-class physicians and scientists are helping pave the way for exciting new cancer treatments to benefit patients with cancer everywhere.”
Although the disease is very rare, Demeure said that developing a new drugs against this orphan indication is worth the effort and expense. “Patients with rare tumors have unique challenges. Often it is difficult for them to find a doctor who even knows about their disease,” he said. “What we learn taking care of those patients with ACC could help us learn how to take care of others with rare tumors.’’
The clinical trial follows nearly 3 1/2 years of research at TGen, initiated through the efforts of patient advocate and ACC survivor, Mr. Troy Richards.
Richards, a Scottsdale resident, has battled ACC since 1999. To combat what little research he saw being done on the disease, he began the Advancing Treatments for Adrenocortical Carcinoma (ATAC) fund, which helped finance the ACC Research Program at TGen.
"The ACC project at TGen has finally given those of us with the disease hope for better treatments, and maybe one day a cure,” said Mr. Richards. “It is my hope that this program can serve as a model for other rare diseases, and that patients will realize they do have the power to make a difference.”
Dr. Kimberly Bussey, a TGen Associate Investigator and Lead Investigator for TGen’s Adrenocortical Carcinoma Research Program, said, “Troy brings a sense of urgency and a connection to the ACC patient community that made this trial possible. This is a huge accomplishment for the ACC Research Program at TGen and a great testament to what patient-advocated research can accomplish in a short period of time.”
“We are eagerly awaiting the opening of this study,” said Dr. Maqbool Halepota, an oncologist with the Palo Verde Hematology/Oncology group based at the Virginia G. Piper Cancer Center at Scottsdale Healthcare. “I firmly believe that targeted therapies are the future of cancer care, and our partnership with TCRS allows patients in the Phoenix area access to many innovative trials.”
For additional information:
The adrenal glands are responsible for making several critical hormones, including cortisol, which the body needs in order to respond to stress and which helps to maintain normal blood sugar levels in children.
Adrenal carcinoma (ACC) affects 1 to 2 per million population annually and may be curable if treated at an early stage. Radical surgical excision is the treatment of choice for localized malignancies and remains the only method by which long-term disease-free survival may be achieved. Overall 5-year survival for tumors resected for cure is approximately 40%. Retrospective studies have identified two important prognostic factors: completeness of resection and stage of disease. The most common sites of metastases are the peritoneum, lung, liver, and bone.
Other than surgery, the only treatment for ACC is the exacting use of a compound called mitotane (Lysodren®, Bristol-Myers Squibb), a chemical relative of DDT, which the U.S. banned as an insecticide in 1972, systemic chemotherapy, or (for localized lesions) radiation therapy.
While use of mitotane in ACC patients reduces tumors, it also diminishes adrenal gland function, requiring patients to take hormone replacements for the rest of their lives. In addition, mitotane must be administered for at least three months in order to reach a therapeutic level. Even then, it has proved effective in about 22% of ACC cases. When given with other chemotherapy drugs, the effectiveness of mitotane may be improved, but patients often suffer debilitating side effects.
Clinicians at TGen Clinical Research Services (TCRS), a strategic alliance between the Translational Genomics Research Institute (TGen) and Scottsdale Healthcare, hope that a new compound, OSI-906, a small molecule IGF-1R inhibitor that blocks the chemical pathway that otherwise allows the ACC tumors to grow out of control.
The drug candidate is developed by OSI Pharmaceuticals Inc. of Melville, N.Y., and will stop ACC tumor growth — perhaps even promote tumor shrinkage — without the toxic side effects of current chemotherapies. The trial will focus on patients with inoperable tumors who have relapsed or failed to respond to conventional therapies.
IGF-1R inhibitor
OSI-906 is a potent, selective orally active inhibitor of the insulin-like growth factor-1 receptor (IGF-1R) which has been viewed as an important therapeutic target due to its involvement in the growth and proliferation in a variety of human cancers, including adrenocortical carcinoma (ACC), ovarian and non-small cell lung cancers.
The new drug candidate stimulates proliferation, enables onogenic transformation, and suppresses apoptosis. Inhibitors of IGF-1R are expected to have broad utility in oncology since the over-expression of IGF-1R and/or its ligands or the down-regulation of ligand binding proteins occurs in numerous human malignancies including lung, colon, breast, prostate, brain and skin cancers. In addition, signaling through the IGF system has been implicated in protecting tumor cells from apoptosis induced by anti-cancer treatments such as cytotoxic agents and EGFR inhibitors. Scientists therefore believe that OSI-906 may be useful both as a single agent and in combination with other targeted therapies such as erlotinib (Tarceva® marketed by Genentech Bioncology and OSI Pharmaceuticals).
Ongoing research
During the 2009 annual meeting of ASCO, the American Society of Clinical Oncology, a number of abstracts were published with IGF-1R inhibitors in a range of cancers, making a case for insulin growth factor receptor (IGF-1R) inhibitors as a potential target for cancer therapeutics. So far, the data presented at ASCO has been very preliminary and isolated responses were seen.
In addition to OSI (OSI-906), a number of pharmaceutical and research companies have active, ongoing research programs in the clinic. Many other companies are involved in preliminary research in different stages in different cancers (Exelixis/XL228, Amgen/AMG-479, Roche/R1507, Pfizer/CP-751,871/Figitumumab, BMS/BMS-754807, Merck/MK-0646, and Imclone/Lilly/IMC A12). Others companies, including Sanofi-Aventis, Novartis, Eisai, Biogen Idec, are interested to see how this new class pans out.
OSI-906 trial
A clinical trial of OSI-906 is expected to last several years and include 135 patients, with 30-40 enrolled at TCRS. As there is no standard therapy available, two-thirds of the patients will receive the drug OSI-906 while one-third receives a placebo. Sites elsewhere in the U.S., as well as in Europe and Australia, are expected to enroll patients over the coming months.
“The trial is major step toward helping patients with ACC, who often face radical surgery as part of their treatment,” said Dr. Michael J. Demeure, who will oversee the trial locally. Dr. Demeure is a TGen Senior Investigator and a Scottsdale Healthcare surgeon experienced in removing ACC tumors.
“It’s a big operation requiring a large incision because these tumors can be the size of a football. Unfortunately many patients’ tumors have spread so we can’t remove it all, so new treatments are needed.’’ Demeure explained. “This unique partnership between Scottsdale Healthcare and TGen allows us to bring the newest and most promising treatments to patients with cancer right here in Arizona.”
The TCRS clinic in the Virginia G. Piper Cancer Center at Scottsdale Healthcare Shea is the first site worldwide approved for these clinical trials.
"Being the first site in the world for clinical trials of this drug adds to the long list of ‘firsts’ for the Virginia G. Piper Cancer Center,” said Mark Slater, Ph.D., vice president of research. "Scottsdale Healthcare’s collaborations with world-class physicians and scientists are helping pave the way for exciting new cancer treatments to benefit patients with cancer everywhere.”
Although the disease is very rare, Demeure said that developing a new drugs against this orphan indication is worth the effort and expense. “Patients with rare tumors have unique challenges. Often it is difficult for them to find a doctor who even knows about their disease,” he said. “What we learn taking care of those patients with ACC could help us learn how to take care of others with rare tumors.’’
The clinical trial follows nearly 3 1/2 years of research at TGen, initiated through the efforts of patient advocate and ACC survivor, Mr. Troy Richards.
Richards, a Scottsdale resident, has battled ACC since 1999. To combat what little research he saw being done on the disease, he began the Advancing Treatments for Adrenocortical Carcinoma (ATAC) fund, which helped finance the ACC Research Program at TGen.
"The ACC project at TGen has finally given those of us with the disease hope for better treatments, and maybe one day a cure,” said Mr. Richards. “It is my hope that this program can serve as a model for other rare diseases, and that patients will realize they do have the power to make a difference.”
Dr. Kimberly Bussey, a TGen Associate Investigator and Lead Investigator for TGen’s Adrenocortical Carcinoma Research Program, said, “Troy brings a sense of urgency and a connection to the ACC patient community that made this trial possible. This is a huge accomplishment for the ACC Research Program at TGen and a great testament to what patient-advocated research can accomplish in a short period of time.”
“We are eagerly awaiting the opening of this study,” said Dr. Maqbool Halepota, an oncologist with the Palo Verde Hematology/Oncology group based at the Virginia G. Piper Cancer Center at Scottsdale Healthcare. “I firmly believe that targeted therapies are the future of cancer care, and our partnership with TCRS allows patients in the Phoenix area access to many innovative trials.”
For additional information:
- Scottsdale Clinical Research Institute
- Scottsdale Healthcare Foundation
- Virginia G. Piper Cancer Center
- TGen Clinical Research Services
Monday, June 1, 2009
An Exclusive Global Alliance for Novel Targeted Oncology Therapies
European pharmaceutical giant Sanofi-aventis and US based Exelixis Inc, a development-stage biotechnology company dedicated to the discovery and development of novel small molecule therapeutics for the treatment of cancer and other serious diseases, announced late last week a global license agreement for XL147 (an orally available small molecule inhibitor of phosphoinositide-3-kinase) and XL765 (an orally available small molecule, dual inhibitor of PI3K and mTOR, which plays a central role in tumor cell proliferation) and an exclusive collaboration for the discovery of inhibitors of phosphoinositide-3 kinase (PI3K) for the management of solid malignancies.
Activation of the PI3K pathway is a frequent event in human tumors, promoting cell proliferation and cell survival, as well as resistance to chemotherapy and radiotherapy.
The phosphoinositide-3-kinase (PI3K) pathway is triggered in normal cells upon exposure to growth factors. It regulates a cascade of proliferation and survival signals. The PI3K pathway is one of the primary deregulated signaling pathways in human cancer. Activation of the PI3K pathway is a frequent event in human tumors, promoting cell proliferation, survival, and resistance to chemotherapy and radiotherapy. Novel therapeutics impacting the PI3K pathway, alone or in combination, are therefore considered to have a high therapeutic potential.
Under the license agreement, Sanofi-aventis will have an exclusive worldwide license to XL147, an oral PI3K inhibitor, and XL765, an oral dual inhibitor of PI3K and mTOR (mammalian target of rapamycin). Both are currently in phase 1 clinical trials. Sanofi-aventis will have sole responsibility for all subsequent clinical, regulatory, manufacturing and commercial activities. Exelixis will participate in ongoing and potential future clinical trials.
Under the exclusive discovery collaboration, sanofi-aventis and Exelixis will combine research efforts to establish several preclinical programs related to isoform-selective inhibitors of PI3K.
Sanofi-aventis will have sole responsibility for all subsequent clinical, regulatory, commercial and manufacturing activities of the products that result from the collaboration. However, Exelixis may be responsible for conducting certain clinical trials.
“We are very excited about integrating such novel targeted therapies with high therapeutic potential in our portfolio,” said Marc Cluzel, Senior Vice-President R&D, Sanofi-aventis. “We look forward to combining our efforts with Exelixis to develop innovative drugs in the best interest of patients suffering from cancers. This alliance is aligned with our strategy to create value through strategicpartnerships that deliver new therapeutic options”.
Under the terms of the agreements, Sanofi-aventis will pay Exelixis an upfront cash payment as well as development and regulatory milestone payments that could reach over $1 billion in aggregate for existing and future programs under both agreements. In addition, Exelixis will be entitled to receive royalties and commercial milestones on sales when products are commercialized.
The license agreement is subject to antitrust clearance under the Hart-Scott-Rodino Antitrust Improvements Act.
Activation of the PI3K pathway is a frequent event in human tumors, promoting cell proliferation and cell survival, as well as resistance to chemotherapy and radiotherapy.
The phosphoinositide-3-kinase (PI3K) pathway is triggered in normal cells upon exposure to growth factors. It regulates a cascade of proliferation and survival signals. The PI3K pathway is one of the primary deregulated signaling pathways in human cancer. Activation of the PI3K pathway is a frequent event in human tumors, promoting cell proliferation, survival, and resistance to chemotherapy and radiotherapy. Novel therapeutics impacting the PI3K pathway, alone or in combination, are therefore considered to have a high therapeutic potential.
Under the license agreement, Sanofi-aventis will have an exclusive worldwide license to XL147, an oral PI3K inhibitor, and XL765, an oral dual inhibitor of PI3K and mTOR (mammalian target of rapamycin). Both are currently in phase 1 clinical trials. Sanofi-aventis will have sole responsibility for all subsequent clinical, regulatory, manufacturing and commercial activities. Exelixis will participate in ongoing and potential future clinical trials.
Under the exclusive discovery collaboration, sanofi-aventis and Exelixis will combine research efforts to establish several preclinical programs related to isoform-selective inhibitors of PI3K.
Sanofi-aventis will have sole responsibility for all subsequent clinical, regulatory, commercial and manufacturing activities of the products that result from the collaboration. However, Exelixis may be responsible for conducting certain clinical trials.
“We are very excited about integrating such novel targeted therapies with high therapeutic potential in our portfolio,” said Marc Cluzel, Senior Vice-President R&D, Sanofi-aventis. “We look forward to combining our efforts with Exelixis to develop innovative drugs in the best interest of patients suffering from cancers. This alliance is aligned with our strategy to create value through strategicpartnerships that deliver new therapeutic options”.
Under the terms of the agreements, Sanofi-aventis will pay Exelixis an upfront cash payment as well as development and regulatory milestone payments that could reach over $1 billion in aggregate for existing and future programs under both agreements. In addition, Exelixis will be entitled to receive royalties and commercial milestones on sales when products are commercialized.
The license agreement is subject to antitrust clearance under the Hart-Scott-Rodino Antitrust Improvements Act.
Thursday, January 8, 2009
Upcoming Phoenix conference highlights 'molecular oncology' for oncologists and their patients
Physician-scientists from the Arizona based Translational Genomics Research Institute (TGen), a non-profit organization dedicated to conducting groundbreaking medical research in with life changing results, and Scottsdale Healthcare, a primary clinical research site for TGen in the Virginia G. Piper Cancer Center in Scottsdale, AZ, will present their latest findings and techniques at a national conference designed to provide cancer doctors with new treatments for their patients.
'Molecular Oncology: The Sixth Vital Sign, What Every Oncologist Should Know' is intended to help oncologists provide better diagnosis, early detection as well as drugs and other treatments that in some cases can slow the growth or even shrink tumors.
'Given the explosion of new information on the genetic and cellular features of malignancy, the modern oncologist must master the significance and application of cancer-related sciences,' said Dr. Ramesh K. Ramanathan, Medical Director of TGen Clinical Research Services at Scottsdale Healthcare, a partnership between TGen and Scottsdale Healthcare Corp.
Personalized Medicine
Beyond the five vital signs of pulse, respiration, temperature, blood pressure and pain, is a new sixth 'vital sign' – molecular therapeutics. This new 'vital sign' offers oncologists the opportunity to identify the causes of disease at the molecular level in order to provide the right drugs in the right amounts at the right times for the specific needs of individual patients. This new approach is becoming better known in health circles as personalized medicine or theragnostics.
However, the the concept that information about a patient's genotype or gene expression profile can be used to tailor medical care to an individual's needs requires understanding of the link between the mechanisms of action of novel therapeutics and specific tumor geneticts, thereby unifying molecular diagnostics and therapeutics.
Given the explosion of new information on the genetic and cellular features of malignancy and the rapidly growing armamentarium of targeted therapeutics, oncologists today must master the understanding, appreciate the significance and value the application of cancer-related basic and clinical sciences. 'This gap in knowledge and its application in clinical practice will be addressed in this conference,' Ramanathan explained.
Dr. Ramanathan is the co-program director of the conference, along with Dr. Daniel Von Hoff, TGen's Physician-In-Chief and the Chief Scientific Officer at TCRS. Both doctors conduct groundbreaking personalized-medicine research and clinical drug trials at TCRS in Scottsdale, and both are on the clinical faculty of the University of Arizona College of Medicine. Both will present at the conference.
Other TGen and Scottsdale Healthcare scientists scheduled to present include: Dr. Jeffrey Trent, TGen's President and Scientific Director; Dr. Raoul Tibes, Director of the Hematological Malignancies Program at TCRS and an Associate Investigator at TGen; Dr. Stephen P. Anthony, Chief Medical Officer of TGen Drug Development Services (TD2) and a Senior Investigator at TGen; Dr. John Carpten, Director of TGen’s Integrated Cancer Genomics Division and a Senior Investigator at TGen; and Gayle Jameson, M.S.N., Director of Supportive Care at TCRS and an Associate Investigator at TGen.
Target audience
Besides oncologists, the target audience includes all physicians and health professionals involved in caring for cancer patients, and researchers interested in new cancer diagnostics and therapeutics.
Key objectives of the conference include:
'Molecular Oncology: The Sixth Vital Sign, What Every Oncologist Should Know' is intended to help oncologists provide better diagnosis, early detection as well as drugs and other treatments that in some cases can slow the growth or even shrink tumors.
'Given the explosion of new information on the genetic and cellular features of malignancy, the modern oncologist must master the significance and application of cancer-related sciences,' said Dr. Ramesh K. Ramanathan, Medical Director of TGen Clinical Research Services at Scottsdale Healthcare, a partnership between TGen and Scottsdale Healthcare Corp.
Personalized Medicine
Beyond the five vital signs of pulse, respiration, temperature, blood pressure and pain, is a new sixth 'vital sign' – molecular therapeutics. This new 'vital sign' offers oncologists the opportunity to identify the causes of disease at the molecular level in order to provide the right drugs in the right amounts at the right times for the specific needs of individual patients. This new approach is becoming better known in health circles as personalized medicine or theragnostics.
However, the the concept that information about a patient's genotype or gene expression profile can be used to tailor medical care to an individual's needs requires understanding of the link between the mechanisms of action of novel therapeutics and specific tumor geneticts, thereby unifying molecular diagnostics and therapeutics.
Given the explosion of new information on the genetic and cellular features of malignancy and the rapidly growing armamentarium of targeted therapeutics, oncologists today must master the understanding, appreciate the significance and value the application of cancer-related basic and clinical sciences. 'This gap in knowledge and its application in clinical practice will be addressed in this conference,' Ramanathan explained.
Dr. Ramanathan is the co-program director of the conference, along with Dr. Daniel Von Hoff, TGen's Physician-In-Chief and the Chief Scientific Officer at TCRS. Both doctors conduct groundbreaking personalized-medicine research and clinical drug trials at TCRS in Scottsdale, and both are on the clinical faculty of the University of Arizona College of Medicine. Both will present at the conference.
Other TGen and Scottsdale Healthcare scientists scheduled to present include: Dr. Jeffrey Trent, TGen's President and Scientific Director; Dr. Raoul Tibes, Director of the Hematological Malignancies Program at TCRS and an Associate Investigator at TGen; Dr. Stephen P. Anthony, Chief Medical Officer of TGen Drug Development Services (TD2) and a Senior Investigator at TGen; Dr. John Carpten, Director of TGen’s Integrated Cancer Genomics Division and a Senior Investigator at TGen; and Gayle Jameson, M.S.N., Director of Supportive Care at TCRS and an Associate Investigator at TGen.
Target audience
Besides oncologists, the target audience includes all physicians and health professionals involved in caring for cancer patients, and researchers interested in new cancer diagnostics and therapeutics.
Key objectives of the conference include:
- Explaining the molecular and cellular features of malignancy in diagnostic and therapeutic approaches to the treatment of cancer, and identifying new diagnostic tools.
- Assessing the effects and early clinical results of new, targeted drug therapies on solid tumors and malignant blood cancers.
- Identifying new drug therapies that optimize treatment results and minimize side effects in specific biologic and clinical scenarios.
- Evaluating clinical trials and translational methods of care and their proper use in clinical decision-making and patient management.
The conference is sponsored by TGen, Scottsdale Healthcare's Virginia G. Piper Cancer Center and Physicians' Education Resource (PER) of Dallas. The conference is certified for Continuing Medical Education.
For more information:
- 'The Sixth Vital Sign' runs Jan. 22-24, 2009 at the Arizona Grand Resort.
- Personalized Medicine Coalition
Also read PubMed abstracts:
- Acharya CR, Hsu DS, Anders CK, Anguiano A, et al. Gene expression signatures, clinicopathological features, and individualized therapy in breast cancer. JAMA 2008 Apr 2;299(13):1574-87. Click here for a full text version of this article.
- Pene F, Courtine E, Cariou A, Mira JP. Toward theragnostics. Crit Care Med. 2009 Jan;37(1 Suppl):S50-8.
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.
Sunday, December 7, 2008
Combining targeted therapy drugs may treat previously resistant tumors
Blocking two cell signaling pathways leads to dramatic shrinkage of K-Ras-mutated tumors in animal model. This is the conclusion of a team of cancer researchers from several Boston academic medical centers. The team believes that their findings offer a potential treatment for a group of tumors that have resisted previous approaches of treatment with selected targeted therapies.
In their report published in the december issue of Nature Medicine, investigators from Dana-Farber Cancer Institute, a principal teaching affiliate of the Harvard Medical School, Massachusetts General Hospital (MGH) Cancer Center, the original and largest teaching hospital of Harvard Medical School and Beth Israel Deaconess Medical Center (BIDMC) Cancer Center, a patient care, teaching and research affiliate of Harvard Medical School, report that combining two different kinase inhibitors, drugs that interfere with specific cell-growth pathways, led to significant tumor shrinkage in mice with lung cancer driven by mutations in the K-Ras gene.
K-ras, which is part of the ras family of oncogenes which also includes H-ras and N-ras, is involved in the development of a variety of human malignancies. The K-ras oncogene resides on chromosome 12p12, and encodes a 21-kD protein (p21ras) involved in the G-protein signal transduction pathway, modulating cellular proliferation and differentiation. The ras pathway is important in the transmission of growth-promoting signals from the cell surface receptors and affect the production and regulation of key proteins. Mutations of the K-Ras gene occur long before the formation of the actual cancer.
Controversial
So far, researchers believe that the clinical significance of K-ras mutations is somewhat controversial. But a number of studies have shown lower median survival times in patients with mutation-positive tumors in gastrointestinal malignancies. As it turns out, K-ras mutations are one of the most common genetic abnormalities in colon, pancreatic cancers and bile duct carcinomas, detectable in greater than 75% of tumors. These cancers are extremely resistant to treatment.
In gynecological malignancies and endometrial carcinomas, K-ras mutations are noted in up to a third of cases. Studies have shown that in postmenopausal women with endometrial carcinomas, K-ras mutations appear to be an independent risk factor for adverse prognosis. Researchers believe that that the presence of K-ras mutations in endometrial hyperplasia specimens may identify a group of patients with a high probability for progression.
K-ras mutations are also associated with nearly 30% of non-small-cell lung cancer, the leading cause of cancer deaths in the United Sates. In limited stage adenocarcinomas, usually is seen peripherally in the lungs, the presence of K-ras mutation is independently associated with more aggressive disease and decreased patient survival.
"Finding a way to effectively treat K-Ras-mutated cancers would be a huge advance in solid tumor oncology, since these mutations are common in several incurable cancers," explained Jeffrey Engelman, MD, PhD, of the MGH Cancer Center, one of the report's co-lead authors. "Cancers with K-Ras mutations have been resistant to all targeted therapies to date, and it is exciting to learn that a combination of PI3K and MEK inhibitors, two families of drugs currently in clinical development, may be highly effective in these cancers."
The current study began with a focus on the PI3K signaling pathway, which is key to cell survival and known to control cellular motility and adhesion. PI3K mutations have caused tumor development in laboratory studies, but their role had not yet been studied in an animal model. The research team developed a transgenic mouse in which administration of the drug doxycycline induces the expression of cancer-associated PI3K mutations, leading to development of lung tumors.
Treatment of those animals with an investigational PI3K inhibitor did lead to rapid tumor regression. Since previous studies suggested that PI3K inhibition might also block K-Ras-induced tumor development, the investigators also tested the PI3K inhibitor in mice with K-Ras-stimulated tumors.
That treatment was ineffective, but since K-Ras also activates the MEK/ERK signaling pathway, the researchers treated the animals with an investigational MEK inhibitor and with a combination of both drugs. Treatment with the MEK inhibitor alone caused only a modest reduction in tumor size, but combined treatment with both agents caused the K-Ras-stimulated lung tumors to virtually disappear.
"For several years we have known that K-Ras activates two major pathways — the PI3K pathway and the MEK/MAPK pathway — and that these pathways have many redundant functions in tumor growth and survival," notes Lewis Cantley, PhD, of the BIDMC Cancer Center, one of the study's co-corresponding authors. Contley continues: "Inhibitors of both of these pathways are now in clinical trials, and in this paper we show that, while either agent alone has a minor effect on K-Ras-driven tumors in mice, combining inhibitors of both pathways eradicates these tumors with minimal toxicity."
Kwok-Kin Wong, MD, PhD, of Dana-Farber, also a co-corresponding author, adds, "The results of our study are truly remarkable and provide a strong and compelling scientific rationale to test this combination therapy in human phase 1 and 2 trials. This work would not have been possible without the highly productive collaboration between our laboratories at Mass. General, Beth Israel Deaconess and Dana-Farber."
Wong is an assistant professor of medicine at Harvard Medical School, where Engelman is also an assistant professor in medicine and Cantley is the Castle Professor of Medicine.
The researchers are hoping to advance towards clinical trials by testing combination therapy against other models of K-Ras-mutated cancer, including those that involve additional mutations in other tumor-associated genes, and to investigate whether K-Ras-associated tumors will become resistant to combination therapy, a problem that has plagued other targeted cancer therapies.
Also read PubMed abstracts:
- Engelman JA, Chen L , Tan X, Crosby K et al. Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Na. Med 2008 Dec;14(12):1351-1356. Epub 2008 Nov 30.
- Zhao L, Vogt PK. Class I PI3K in oncogenic cellular transformation. Oncogene 2008 Sep 18;27(41):5486-96.
- Yuan TL, Cantley LC . PI3K pathway alterations in cancer: variations on a theme. Oncogene 2008 Sep 18;27(41):5497-510.
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