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
Showing posts with label patients. Show all posts
Showing posts with label patients. Show all posts
Monday, October 25, 2010
Wednesday, December 16, 2009
Denosumab Superior to Zoledronic Acid in Reducing Incidence of Skeletal-Related Events in Breast Cancer Patients with Bone Metastases
Data Presented at earlier this month at the San Antonio Breast Cancer Symposium demonstrates that treatment with denosumab, a new drug in late stage clinical development, is superior to the standard of care in advanced breast cancer patients. Among patients with bone metastasis from breast cancer, denosumab was superior to zoledronic acid in reducing the incidence of complications from bone metastases.
"Denosumab prevented more events, was better tolerated and is more convenient for patients," said Alison Stopeck, M.D., associate professor of medicine at the University of Arizona Cancer Center who presented the results of this phase III, double blind study at the 2009 CTRC-AACR San Antonio Breast Cancer Symposium.
Stopeck and colleagues enrolled 2,048 patients with bone metastasis who had never received treatment with intravenous bisphosphonates. They randomly assigned patients to treatment with 120 mg subcutaneous denosumab (Amgen) or 4 mg intravenous zoledronic acid (Zometa, Novartis) every four weeks.
Denosumab, is an investigational first fully human monoclonal antibody developed by Amgen. It works differently from existing bone treatments by specifically targeting a protein called RANK Ligand (RANKL), which plays an important role in regulating osteoclast activity and function and has been linked with increased bone loss and complications from bone metastases.
Stopeck presented data confirming that denosumab significantly delayed time to first on-study skeletal-related event compared with zoledronic acid (HR=0.82; 95% CI, 0.71-0.95), as well as time to first, and subsequent, on-study skeletal-related event (rate ratio=0.77; 95% CI, 0.66-0.89). In this study, patients assigned to denosumab had 491 skeletal-related events compared with 623 for patients assigned to zoledronic acid.
"In clinical trials testing new medications for bone metastases, treatment success is measured by whether the bone complications, or skeletal related events, caused by the tumor are reduced or delayed," Stopeck explained. "Skeletal complications from bone metastases are a critical and painful health concern for patients with advanced breast cancer, and can increase the risk of mortality. Patients who have a first skeletal related event are twice as likely to experience a subsequent SRE, so it is imperative to treat these advanced breast cancer patients."
“Denosumab resulted in a considerable delay in the development of moderate-to-severe pain compared to zoledronic acid,” Stopeck said.
Additional data from this study showed that denosumab significantly reduced the mean annual skeletal morbidity rate (SMR) (the ratio of the number of skeletal complications to the time on trial) compared with Zometa (0.45 vs. 0.58, respectively; p=0.004).
Overall, the incidence of adverse events (96% denosumab, 97% zoledronic acid) and serious adverse events (44% denosumab, 46% zoledronic acid) was consistent with what has previously been reported for these two agents. Adverse events potentially associated with acute phase reactions during the first three days of the study were reported in 10.4 percent of the denosumab arm and 27.3% of the zoledronic acid arm. Adverse events potentially associated with renal toxicity occurred in 4.9% of patients treated with denosumab compared to 8.5% in patients treated with zoledronic acid.
Osteonecrosis of the jaw (ONJ) was seen infrequently in both treatment groups (20 patients receiving denosumab [2.0%] as compared with 14 patients [1.4%t] receiving Zometa). Rates of new primary malignancies were similar between treatment arms (5 patients receiving denosumab [0.5%] and 5 receiving zoledronic acid [0.5%]). Time to disease progression or overall survival was balanced between the study arms.
At 34 months, 30.7% of patients treated with denosumab arm experienced at least one skeletal-related event (95% CI, 33.5%-39.4%) compared with 36.5% of those treated with zoledronic acid. Denosumab also reduced mean skeletal morbidity rate (0.45 vs. 0.58; P=.004).
Clinical relevance
Bone metastases, cancer cells that separate from tumors and migrate to bone tissue where they settle and grow, occur in more than 1.5 million people worldwide. With improvements in cancer care, including earlier diagnosis and new treatment options, leading to increases in survival rates, the number of patients developing metastatic disease secondary to a primary cancer is increasing. Bone metastases are a significant problem for patients with certain types of advanced cancer, with incidence rates of nearly 100 percent in myeloma patients and as high as 75 percent in breast and prostate cancer patients.
With bone metastases the growing cancer cells weaken and destroy the bone around the tumor. The damage the tumor has caused to the bone can result in a number of serious complications, collectively called SREs. These include fracture of a bone, the need for radiation to bone, the need for bone surgery, or spinal cord compression. All are serious complications for advanced cancer patients.
The economic burden of United States (U.S.) patients with bone metastases is significant and was estimated to be $12.6 billion last year. Patients with bone metastases who experience an SRE incur significantly higher medical costs compared with those who do not experience an SRE.
The results of this study are therefore clinically relevant. Before the availability of bisphosphonates 64% patients with breast cancer with bone metastases generally developed a skeletal-related event, including fracture or pain. With the introduction of Bisphosphonates, this was reduced this to 43%. Today, with more potent agents such as zoledronic acid, the development of skeletal-related event are less than 34%. The results of this trial comparing denosumab vs zoledronic acid shows further improvement with a 27% reduction of incidence rate.
This oral presentation of the denosumab 136 data by Dr. Alison Stopeck was presented at the 2009 CTRC-AACR San Antonio Breast Cancer Symposium. on Thursday, December 10 at 3:15 PM (CT) in Exhibit Hall D of the Henry B. Gonzalez Convention Center, San Antonio, Texas.
For more information
"Denosumab prevented more events, was better tolerated and is more convenient for patients," said Alison Stopeck, M.D., associate professor of medicine at the University of Arizona Cancer Center who presented the results of this phase III, double blind study at the 2009 CTRC-AACR San Antonio Breast Cancer Symposium.
Stopeck and colleagues enrolled 2,048 patients with bone metastasis who had never received treatment with intravenous bisphosphonates. They randomly assigned patients to treatment with 120 mg subcutaneous denosumab (Amgen) or 4 mg intravenous zoledronic acid (Zometa, Novartis) every four weeks.
Denosumab, is an investigational first fully human monoclonal antibody developed by Amgen. It works differently from existing bone treatments by specifically targeting a protein called RANK Ligand (RANKL), which plays an important role in regulating osteoclast activity and function and has been linked with increased bone loss and complications from bone metastases.
Stopeck presented data confirming that denosumab significantly delayed time to first on-study skeletal-related event compared with zoledronic acid (HR=0.82; 95% CI, 0.71-0.95), as well as time to first, and subsequent, on-study skeletal-related event (rate ratio=0.77; 95% CI, 0.66-0.89). In this study, patients assigned to denosumab had 491 skeletal-related events compared with 623 for patients assigned to zoledronic acid.
"In clinical trials testing new medications for bone metastases, treatment success is measured by whether the bone complications, or skeletal related events, caused by the tumor are reduced or delayed," Stopeck explained. "Skeletal complications from bone metastases are a critical and painful health concern for patients with advanced breast cancer, and can increase the risk of mortality. Patients who have a first skeletal related event are twice as likely to experience a subsequent SRE, so it is imperative to treat these advanced breast cancer patients."
“Denosumab resulted in a considerable delay in the development of moderate-to-severe pain compared to zoledronic acid,” Stopeck said.
Additional data from this study showed that denosumab significantly reduced the mean annual skeletal morbidity rate (SMR) (the ratio of the number of skeletal complications to the time on trial) compared with Zometa (0.45 vs. 0.58, respectively; p=0.004).
Overall, the incidence of adverse events (96% denosumab, 97% zoledronic acid) and serious adverse events (44% denosumab, 46% zoledronic acid) was consistent with what has previously been reported for these two agents. Adverse events potentially associated with acute phase reactions during the first three days of the study were reported in 10.4 percent of the denosumab arm and 27.3% of the zoledronic acid arm. Adverse events potentially associated with renal toxicity occurred in 4.9% of patients treated with denosumab compared to 8.5% in patients treated with zoledronic acid.
Osteonecrosis of the jaw (ONJ) was seen infrequently in both treatment groups (20 patients receiving denosumab [2.0%] as compared with 14 patients [1.4%t] receiving Zometa). Rates of new primary malignancies were similar between treatment arms (5 patients receiving denosumab [0.5%] and 5 receiving zoledronic acid [0.5%]). Time to disease progression or overall survival was balanced between the study arms.
At 34 months, 30.7% of patients treated with denosumab arm experienced at least one skeletal-related event (95% CI, 33.5%-39.4%) compared with 36.5% of those treated with zoledronic acid. Denosumab also reduced mean skeletal morbidity rate (0.45 vs. 0.58; P=.004).
Clinical relevance
Bone metastases, cancer cells that separate from tumors and migrate to bone tissue where they settle and grow, occur in more than 1.5 million people worldwide. With improvements in cancer care, including earlier diagnosis and new treatment options, leading to increases in survival rates, the number of patients developing metastatic disease secondary to a primary cancer is increasing. Bone metastases are a significant problem for patients with certain types of advanced cancer, with incidence rates of nearly 100 percent in myeloma patients and as high as 75 percent in breast and prostate cancer patients.
With bone metastases the growing cancer cells weaken and destroy the bone around the tumor. The damage the tumor has caused to the bone can result in a number of serious complications, collectively called SREs. These include fracture of a bone, the need for radiation to bone, the need for bone surgery, or spinal cord compression. All are serious complications for advanced cancer patients.
The economic burden of United States (U.S.) patients with bone metastases is significant and was estimated to be $12.6 billion last year. Patients with bone metastases who experience an SRE incur significantly higher medical costs compared with those who do not experience an SRE.
The results of this study are therefore clinically relevant. Before the availability of bisphosphonates 64% patients with breast cancer with bone metastases generally developed a skeletal-related event, including fracture or pain. With the introduction of Bisphosphonates, this was reduced this to 43%. Today, with more potent agents such as zoledronic acid, the development of skeletal-related event are less than 34%. The results of this trial comparing denosumab vs zoledronic acid shows further improvement with a 27% reduction of incidence rate.
This oral presentation of the denosumab 136 data by Dr. Alison Stopeck was presented at the 2009 CTRC-AACR San Antonio Breast Cancer Symposium. on Thursday, December 10 at 3:15 PM (CT) in Exhibit Hall D of the Henry B. Gonzalez Convention Center, San Antonio, Texas.
For more information
- Downey L, Livingstone R, Stopeck A. Diagnosing and treating breast cancer in elderly women: a call for improved understanding. J Am Geriatr Soc 2007 Oct;55(10):1636-44. Epub 2007 Aug 28.
- Coleman R. Potential use of bisphosphonates in the prevention of metastases in early-stage breast cancer. Clin Breast Cancer 2007 Jul;7 Suppl 1:S29-35
- Coleman R. On the horizon: can bisphosphonates prevent bone metastases? Breast. 2007 Dec;16 Suppl 3:S21-7. Epub 2007 Nov 7. Review.
- Coleman RE. The benefits and costs of bisphosphonates. J Support Oncol 2007 Nov-Dec;5(10):483-4.
- Brown JE, Coleman RE. The present and future role of bisphosphonates in the management of patients with breast cancer. Breast Cancer Res. 2002;4(1):24-9. Epub 2001 Nov 26. Review.
- Rosen LS, Gordon D, Kaminski M, Howell A, Belch A, et al. Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase III, double-blind, comparative trial. Cancer J. 2001 Sep-Oct;7(5):377-87.
- Coleman RE. Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev. 2001 Jun;27(3):165-76. Review.
- Capanna R, Coia LR, Coleman R. et al. eds. Textbook of Bone Metastases
Hoboken, NJ: Edition: John Wiley and Sons; 2005:105.
- Mundy GR. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer. 2002 Aug;2(8):584-93. Review
- Schulman KL, Kohles J. Economic burden of metastatic bone disease in the U.S. Cancer. 2007 Jun 1;109(11):2334-42.
- Mortimer JE, Schulman K, Kohles JD. Patterns of bisphosphonate use in the United States in the treatment of metastatic bone disease. Clin Breast Cancer. 2007 Aug;7(9):682-9.
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.
Subscribe to:
Posts (Atom)
Posts
