RandyW Posted November 10, 2007 Share Posted November 10, 2007 Three Anemia Drugs To Get Stronger Warning Labels 09 Nov 2007 Warning labels on three anemia drugs used by one million Americans undergoing chemotherapy or who have kidney failure have been strengthened to alert users about increased risk of heart attack, stroke, a worsening of their condition, and even death, said the manufacturers, Amgen and Johnson & Johnson earlier this week. The decision, which has been made in consultation with the US Food and Drug Administration, affects Amgen's Epogen and Aranesp, and Johnson & Johnson's Procrit. These drugs belong to a class known as erythropoiesis-stimulating agents or ESAs. ESAs are a bioengineered protein similar to one made in the kidneys that causes bone marrow to produce more red blood cells. Concern about ESAs has been growing since a number of studies has revealed an increased risk of death in cancer patients with anemia that did not arise as a result of chemotherapy, that kidney dialysis patients could be overusing them, and that they increase tumour growth and reduce survival. The US Food and Drug Administration (FDA) said yesterday, Thursday 8th November, that it had approved revised boxed warnings and other labelling changes for Aranesp, Epogen and Procrit because of the increased risks to patients with cancer and chronic kidney failure. Epogen, Procrit and Aranesp are approved by the FDA for the treatment of anemia in certain cancer patients with anemia caused by chemotherapy, and for the treatment of anemia in patients with chronic kidney failure. The three drugs are also FDA approved for treatment of certain cases of anemia in patients who are about to have major surgery, in order to reduce the need for blood transfusions. And they are also approved for HIV patients with anemia caused by zidovudine (AZT) therapy, said the FDA. The new warnings add to the changes made in March this year, include advice from FDA advisory panels, and say that ESAs do not show reductions in symptoms of anemia, fatigue and quality of life in patients with cancer. The changes in March reflected the resuts of six studies that showed survival was reduced and tumours developed more rapidly when cancer patients were given ESAs targeted at hemoglobin levels of 12 grams per deciliter (g/dL) or more. The latest warnings tell cancer patients that recent studies showed tumour growth and reduced survival in patients with advanced breast, head and neck, lymphoid and non small-cell lung cancer who took ESAs to reach a hemoglobin target of 12 g/dL or more. The warnings also stress there is no evidence that the same risks are present for patients taking ESAs to reach lower targets than 12 g/dL, which is believed to be the more common level reached in clinical practice, said the FDA. Doctors look at a patient's hemoglobin count and recommend the dose of ESA to raise that count to a certain target level. Dr Janet Woodcock, the FDA's deputy commissioner for scientific and medical programs, who is also the chief medical officer and acting director of its Center for Drug Evaluation and Research, said that doctors prescribing ESAs for patients with cancer should take into account the risk of increased tumour growth and reduced survival. "ESAs should be used in patients with cancer only when their anemia is due to chemotherapy and only at the lowest dose necessary to avoid the need for blood transfusions," she said. The warnings specify that ESAs should not be used by cancer patients unless their anemia was caused by chemotherapy, and that they should stop taking ESAs once the chemotherapy has finished. Further trials are to be carried out to test different doses of ESAs on a range of tumour types. The new labels also warn there is no evidence that ESAs improved symptoms of anemia, quality of life, fatigue, or well-being in controlled trials with cancer patients or HIV patients on AZT therapy. For kidney failure patients, the new warnings say that ESAs should not be used to attain a hemoglobin level above the 10 g/dL to 12 g/dL target range. They state that maintaining levels above this range increases the risk of stroke, heart attack, heart failure, and death. They also contain precise instructions on dosage and hemoglobin monitoring for patients with chronic kidney failure whose hemoglobin levels are not responding well to ESA treatment. A new Medication Guide will also be issued to update patients on the safety and effectiveness of ESAs. Click here for FDA. Written by: Catharine Paddock Copyright: Medical News Today Not to be reproduced without permission of Medical News Today -------------------------------------------------------------------------------- Article URL: http://www.medicalnewstoday.com/articles/88232.php Main News Category: Regulatory Affairs / Drug Approvals Also Appears In: Cancer / Oncology, Urology / Nephrology, Blood / Hematology, -------------------------------------------------------------------------------- Quote Link to comment Share on other sites More sharing options...
gpawelski Posted November 13, 2007 Share Posted November 13, 2007 EPO is a natural substance made by the kidney. It stimulates the bone marrow to make red blood cells. Healthy adults are usually at about 15 grams a deciliter. It looks like increasing the hemoglobin level above 12 is very risky with pharmaceutical EPO. Pharmaceutical EPO make sludgy blood. when blood gets too thick they can die of heart attacks and strokes. There is some evidence that clots were not the problem in previous trials, but that EPO may spur tumor growth (it is a growth factor afterall). A growth factor is about twenty small proteins that attach to specific receptors on the surface of stem cells in bone marrow and promote differentiation and maturation of these cells into morphotic constituents of blood. Blood is a circulating tissue composed of fluid plasma and cells (red blood cells, white blood cells, platelets). Problems with blood composition or circulation can lead to downstream tissue (which is made up of cells) dysfunction. If pharmaceutical EPO stimulates the bone marrow to make red blood cells, it could feed the growth of tumors in cancer patients. Some studies suggest that certain tumor cells, such as those in head and neck cancer, have proteins on their surface that bind to EPO. When that happens, it sets off a cascade of reactions spurring growth. Studies done by Dr. Jennifer R. Grandis, professor at the University of Pittsburgh, found enough biologic possibility that they can serve as a growth factor for the cancer cell. The FDA backed CMS' National Coverage Decision (NCD), which limited use of the drugs because they have been shown to spur tumor growth. The FDA has stated that the health risks associated with the use of pharmaceutical EPO (ESAs) for cancer patients include: Promotion of tumor growth in patients with advanced breast, head and neck, lymphoid, and non-small cell lung malignancies in studies adminstered EPO to target a hemoglobin of >12 g/dL, and have not been excluded with lower target hemoglobin levels. FDA's approved labeling recommends use of the lowest dose necessary to avoid the need for blood transfusions and transfusions are not normally given to patients whose hemoglobin is 10 g/dL or higher. The recommendation in the approved labeling that the hemoglobin not exceed 12 g/dL in cancer patients "is intended as an upper safety limit, not a target for therapy." Lee Newcomer, with United Health Group, had stated at the 12th annual conference of the National Comprehensive Cancer Network, 44% of patients having blood work-ups indicated they were not anemic. Len Lichtenfeld, deputy chief medical officer for the American Cancer Society, reiterated that Newcomer was right on the spot on this. Few drugs work the way we think and few physicians/scientists take the time to think through what it is they are using them for. A New York Times article stated that anemia drugs, given by injection, have been heavily advertised, and there is evidence that they have been overused, in part because oncologists can make money by using more of the drug. Lichtenfeld told United Press International, "Probably more than a billion dollars is spent on erythropoietin each year, which makes it one of the most expensive cancer drugs." According to Dr. John Glaspy, director of UCLA's Outpatient Oncology Clinic, one complicating factor, experts say, is that oncologists make significant revenue buying cancer drugs from manufacturers and charging patients a higher price for receiving the drugs in their offices. That profit motive could influence some doctors' decisions. Let's take physicians out of the retail pharmacy business and force them to be physicians again! Quote Link to comment Share on other sites More sharing options...
gpawelski Posted January 4, 2008 Share Posted January 4, 2008 Most doctors and patients would agree the drugs are very helpful for patients when used to correct "severe" anemia, which can be debilitating and even life-threatening. The drugs reduce the need for somewhat risky blood transfusions and can give patients more energy and improve their quality of life. ''These are drugs that were presumed to be entirely safe, given for supportive care and to improve quality of life,'' not to actually treat cancer, said Dr. Eric Winer, director of breast oncology center at the Dana-Farber Cancer Institute in Boston. ''So any concern that they could shorten someone's life are taken quite seriously.'' There is little evidence that the drugs make much difference for patients with "moderate" anemia. Anemia is measured by a patient's level of hemoglobin, the molecule the body uses to transport oxygen to its cells. Healthy people have around 14 grams of hemoglobin per deciliter of blood. Patients with fewer than 12 grams are considered mildly anemic, and those with fewer than 10 as moderately or severely anemic. The labels on the drugs approved by the FDA encourage doctors to aim for a hemoglobin level of 10 to 12. Critics of the drugs say their increased use has been driven by profit. According to Dr. John Glaspy, director of UCLA's Outpatient Oncology Clinic, one complicating factor is that oncologists make significant revenue buying cancer drugs from manufacturers and charging patients a higher price for receiving the drugs in their offices. That profit motive could influence some doctors' decisions. Len Lichtenfeld, deputy chief medical officer for the American Cancer Society, told UPI last year that "probably more than a billion dollars is spent on erythropoietin each year, which makes it one of the most expensive cancer drugs." A six-month course of treatment can cost more than $10,000 per patient. After this issue had started to be reported, U.S. Oncology took an 8-10 million dollar hit in its first-quarter SEC report last year, including reduced pre-tax income due to lower use of anemia drugs. They also were handicapped by CMS stopping the Medicare Demonstration Project which paid chemotherapy providers $130 per report, per infusional-chemotherapy recipient, on a patient's level of nausea, vomiting, pain and fatigue, something that Congress found out that they were supplying free of charge anyway. A continuance of the Medicare Demonstration Project would have exacerbated existing economic and clinical problems instead of resolving them by increasing the temptations for physicians to overuse injectable drugs and promise to aggravate the economic problems Congress attempted to fix with the new Medicare law. A New York Times article reported last year that Federal laws bar drug companies from paying doctors to prescribe medicines that are given in pill form and purchased by patients from pharmacies. However, companies can rebate part of the price that doctors pay for drugs, like the anemia medicines, which they dispense in their offices as part of treatment. Doctors receive the rebates after they buy the drugs from the companies, but they also receive reimbursement from Medicare or private insurers for the drugs, often at a markup over the doctors' purchase price. Although the new Medicare bill tried to curtail this kind of drug concession, private insurers still go along with it. What needs to be done is to remove the profit incentive from the choice of drug treatments. Let's take physicians out of the retail pharmacy business and force them be doctors again! Quote Link to comment Share on other sites More sharing options...
RandyW Posted January 4, 2008 Author Share Posted January 4, 2008 FDA Reports New Risks Posed by Anemia Drugs ESAs can spur faster cancer growth and earlier death, agency says By Steven Reinberg Posted 1/3/08 THURSDAY, Jan. 3 (HealthDay News) -- Two new studies offer further evidence of the health risks posed by the anemia drugs known as erythropoiesis-stimulating agents (ESAs), U.S. officials announced Thursday. Related News Video: Health News & Features Join a Discussion More from Health The studies showed that patients with breast or advanced cervical cancer who took the drugs as treatment for chemotherapy-induced anemia died sooner or had more rapid tumor growth than patients not on the drugs, U.S. Food and Drug Administration officials said in a prepared statement. On Nov. 8, the FDA approved new "black box" warnings on labels of the three ESAs -- Aranesp, Epogen and Procrit. The warnings detailed the dangers to patients with cancer and patients with chronic kidney failure. Those dangers include heart attack, stroke, heart failure and cancer tumor growth and shortened survival, the FDA said. The drugs had been touted as a treatment to lessen fatigue and improve quality of life among cancer, HIV and other patients with anemia, but the revised label said there was no evidence to back that claim. The label change was the fifth such change since Procrit was approved in 1989, FDA officials said. Results of the two studies released Thursday were not among the six studies that led to the Nov. 8 label revision. Taken together, all eight studies show more rapid tumor growth or shortened survival when patients with breast, non-small cell lung, head and neck, lymphoid or cervical cancers received ESAs compared to patients who didn't get this therapy, the FDA said. The FDA said it plans to discuss the new findings and re-examine the risks and benefits of ESAs for patients with chemotherapy-induced anemia at a public advisory committee meeting in the next few months. "This new information further underscores the safety concerns regarding the use of ESAs in patients with cancer, which FDA addressed in previous communications," Dr. Janet Woodcock, the FDA's deputy commissioner for scientific and medical programs, chief medical officer, and acting director of the Center for Drug Evaluation and Research, said in the statement. "FDA is reviewing these data and may take additional action. In the meantime, FDA recommends that health care providers review the risks and benefits of ESAs outlined in the product label and discuss this information with their patients." According to the FDA statement: On Nov. 30, Amgen Inc., manufacturer of the three ESAs -- Aranesp, Epogen, and Procrit -- provided the FDA with information from the 733-patient PREPARE study of women who received chemotherapy before undergoing surgery for breast cancer. After three years, 14 percent of the patients who received Aranesp to treat their anemia had died, compared to 9.8 percent who did not get the drug. Tumor growth was also faster in patients receiving Aranesp. On Dec. 4, Amgen informed the FDA of the results of a study by the National Cancer Institute's Gynecologic Oncology Group of patients receiving chemotherapy and radiation for advanced cervical cancer. The patients were given either Procrit to maintain hemoglobin levels above 12 grams per deciliter of blood or blood transfusions as needed. After three years, 66 percent of the patients who did not take Procrit were alive and free of cancer growth, compared to 58 percent who had received the drug. In announcing the label revision in November, Dr. John Jenkins, director of the FDA's Office of New Drugs, said, "We are emphasizing that ESAs should be used at the lowest dose necessary to avoid blood transfusions, since that is the only identifiable benefit for ESAs. Doctors should have discussions with their patients about whether to use ESAs at all." The three drugs are synthetic versions of a protein made in the kidney that tells bone marrow to produce red blood cells. The drugs are manufactured by Amgen, of Thousand Oaks, Calif. Procrit is marketed and distributed by Ortho Biotech LP of Bridgewater, N.J., a subsidiary of Johnson & Johnson. For cancer patients, November's revised warnings emphasized that the drugs can cause tumor growth and reduce survival among patients with advanced breast, head and neck, lymphoid and non-small cell lung tumors. This is especially true when the dose is designed to produce a hemoglobin level of 12 grams per deciliter of blood or more. For hemoglobin levels less than 12 grams per deciliter, the label says there's no evidence to determine if the drugs cause any of these problems, the FDA said. The revised label also made it clear that ESAs should be used in cancer patients only when their anemia is caused by chemotherapy and not from other causes. Also, ESAs should be stopped when the patient's chemotherapy has ended, the FDA said. The revised label also said there's no evidence that ESAs improve symptoms of anemia, quality of life, fatigue, or patient well-being in cancer patients or patients with HIV taking the drug AZT. More information For more information on ESAs, visit the U.S. Food and Drug Administration. Copyright © 2007 ScoutNews, LLC. All rights reserved. Quote Link to comment Share on other sites More sharing options...
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