Cary Posted June 9, 2004 Share Posted June 9, 2004 http://tinyurl.com/38bky Doctors argue over use of placebos in cancer trials By AMY DOCKSER MARCUS The Associated Press 6/8/04 9:15 AM The Wall Street Journal In a controversial shift, some of the most promising new cancer drugs are heading into clinical trials where only some patients will get the actual drug. Other patients will be given a placebo. The use of placebos is a sharp departure from past practices and is strongly opposed by some influential cancer researchers. Placebo trials generally haven't been used in life-threatening diseases such as cancer. If there is any kind of effective therapy available, the argument goes, it is unethical to give a placebo. Now, drug makers including Bayer Pharmaceuticals Corp., Pfizer Inc. and Genentech are adding placebo arms to their trials in an effort to speed promising new drugs to market. Because placebo trials make it easier to verify results, the strategy can cut down on the need for additional studies and lead to faster regulatory approval. Many in the cancer community are angry about the new approach, saying that it denies desperately ill people a last best hope. Some leading cancer centers, including the M.D. Anderson Cancer Center in Houston and the University of Michigan Cancer Center in Ann Arbor, have refused to put patients in clinical trials that use placebos. Patient-advocacy groups have met with drug makers including Pfizer and Bayer in an effort to change their minds about running trials with placebo arms. Some of the most high-profile new drugs used placebo arms in recent trials, including OSI Pharmaceuticals, Genentech and Roche Group's Tarceva for lung cancer and Bayer and Onyx Pharmaceuticals Inc.'s BAY 43-9006 for kidney cancer. A Pfizer drug being tested for gastrointestinal stromal tumor (GIST) also has run a recent trial with a placebo arm. At the American Society of Clinical Oncology meeting this weekend, researchers presented positive results from the Tarceva and BAY 43-9006 trials. The practice of using placebos in a study -- whereby some patients get the active drug, but others are given look-alike sugar pills and no treatment -- is the gold standard for drug research in many fields of medicine. The strategy makes it much easier to determine whether it is the drug, and not some other factor, that is making the difference in patients. The U.S. Food and Drug Administration, responding to patients' concerns, has developed accelerated approval processes to speed drugs to needy patients even without placebo-based trials. Richard Pazdur, director of the FDA's oncology-drug products, says "we have not insisted that trials be placebo controlled." Drug companies say that such accelerated approval still requires certain additional trials that add to what already is an estimated $800 million price tag to bring a drug to market. And the research still takes longer to accomplish. In addition to patients' meetings with Pfizer and Bayer in the past few months, other efforts are under way by patient advocates to influence trial design. A GIST patient-advocate organization, the Life Raft Group, has set up a Clinical Trials Advisory Group of cancer patients to lobby drug companies against placebo trials. In November, three major professional organizations of cancer clinicians, oncologists and researchers will meet to come up with better ways to design trials for the new therapies that are emerging. All this comes amid growing concern that it is getting harder to get patients to participate in cancer-drug studies in the first place. Just 3 percent of adult cancer patients enroll in clinical trials, according to the President's Cancer Panel report issued last week. A number of national organizations, including the National Cancer Institute, the Lance Armstrong Foundation and the National Coalition for Cancer Survivorship, all are trying to increase the percentage of adult cancer patients who enroll in trials. What all these groups have found is that one reason patients don't enroll is fear of getting a placebo, so the outcome of this current debate is sure to affect recruitment efforts. The University of Michigan Cancer Center in Ann Arbor, along with the M.D. Anderson Cancer Center in Houston, both refused to participate in Pfizer's clinical trial for GIST patients because of their concerns over the trial's placebo arm. "There is almost no good reason to ever do a placebo trial in cancer," says Laurence Baker, director of clinical research at the University of Michigan center. "The only advantage is expediency to the drug manufacturer." When OSI Pharmaceuticals ran recent Phase III clinical trials for its drug Tarceva, for advanced lung cancer, the company didn't include any U.S. sites, concluding "it would take too long to enroll patients" because of the trial's placebo arm, according to OSI Pharmaceuticals Chief Executive Colin Goddard. This meant that patients here lost early access to a potentially beneficial drug. The company reported this weekend at ASCO that the drug extended the lives of patients who took it. Mr. Goddard acknowledged that patients on placebo died more quickly than those with the drug. But that "thanks to the sacrifice of those patients, we've taken lung-cancer treatment forward," Mr. Goddard said. "Future patients will benefit." Some drug companies say they are working to come up with innovative trial designs. In the current Phase III trials for Pfizer's GIST drug, called SU-11,258, doctors are allowed to intervene if a patient's tumor grows more than 20 percent. If it turns out the patient wasn't receiving the active drug, the patient is allowed to "cross over" to the drug arm and begin receiving the medicine. "We tried to minimize the number of people getting a placebo," says Charles Baum, the global clinical leader for the drug at Pfizer. Bernie Kaplan, 64, who was diagnosed with GIST in 2000 is enrolled in the Pfizer trial. When the first assessment showed that his tumors had grown, "I was praying I was on placebo," he says. It turned out he had been given a sugar pill. When he started receiving the drug, his tumors shrank. Many pharmaceutical companies say the very nature of these new cancer drugs makes it imperative to have a placebo arm for comparison. Unlike traditional chemotherapy, which is designed to shrink or eradicate tumors, many of these drugs aim to stop or slow tumors' growth and allow someone to live with their cancer. This makes it harder to measure if it is the drug that is working, or whether someone simply has a less-aggressive tumor. In addition, some of the diseases these drugs are targeted at have no other therapy against which a new drug can be compared. Bayer, which is testing its BAY 43-9006 in kidney-cancer patients, adopted a placebo-trial design in its Phase III trial of the drug that began in October 2003. This weekend, the company reported extremely promising results with an earlier-phase trial of the drug -- 37 out of 106 kidney-cancer patients had their tumors shrink 25 percent or more, and 38 had stable disease. Early positive results such as this make patient-advocate groups even angrier that some patients in later trials won't get any drug, effectively meaning they will die. A group of patients met with Bayer in December to discuss the trial design but, says patient advocate Steve Dunn, "they wouldn't budge." Susan L. Kelley, Bayer's vice president for product development in oncology, says pharmaceutical companies are trying to do the right thing. She says there are no options for kidney-cancer patients against which to compare the new drug. And, Dr. Kelley says, the company cannot allow patients on placebo whose tumors grow to then receive the drug, because "it would confound our ability to follow survival. We need definitive evidence that the drug is active." Quote Link to comment Share on other sites More sharing options...
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