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April 2009 Volume 3 #2
 CAM: Heart health and PCa Buyer beware: CAM's dark side Immunotherapy: An overview CPCN Conference 2009 |
Immunotherapy: An Overview  By David L.B. MacQuarrieJust a few days ago, on April 14, 2009, Dendreon Corporation announced that its prostate cancer vaccine Provenge prolonged the survival of men with advanced prostate cancer. Well, actually, the press release said that the company's "pivotal Phase 3 IMPACT study of PROVENGE® (sipuleucel-T) in men with advanced prostate cancer met its primary endpoint of improving overall survival compared to a placebo control." Both mean approximately the same thing. The company's stock shot up, even though the U. S. Food and Drug Administration (FDA) may request a confirmatory trial. Why might it make this request? Provenge is the first vaccine immunotherapy up for FDA approval. The GVAX vaccine failed in late-stage clinical trials last year. "The successful outcome from the Phase 3 IMPACT study provides validation of the long-pursued goal of harnessing the human immune system against a patient's own cancer," said Dr. Mitchell H. Gold, president and CEO of Dendreon. But what is immunotherapy? And how might it help in the fight against prostate cancer? To understand the theory behind immunotherapy, you will find it helpful to get a clear picture of what it is exactly that the body's immune system does. The body's immune system is designed to fight off invading cells that it thinks might harm you. In fact, every day, the immune system might detect and destroy dozens of microscopic bacteria and viruses. For the immune system to be able to recognise the bacteria and viruses as harmful, however, it must be exposed to them. Only after exposure does it learn to recognise these attackers as harmful and worth fighting. Unfortunately, the immune system is not quite as efficient when it comes to fighting off some invaders, including cancers. So researchers are looking for ways to teach the body how to recognise cancer as dangerous, and they are turning to the history of vaccine development for answers. As noted, the only way that your immune system can learn to fight off a new invader is for it to be exposed to it. But being exposed to some bacteria or viruses, even once, can be life threatening. For this reason, then, scientists from the eighteenth century to the present have developed preventive vaccines to teach the body how to fight particularly dangerous invaders. Preventive vaccines might contain a weakened virus, a killed whole virus, or just a small part of a virus. The idea is to get your body to develop a way to fight that virus off should you come into contact with it again. Few cancers are caused by bacteria or viruses, so, for the most part, developing preventive vaccines for cancer isn't very practical. But therapeutic vaccines that stimulate the immune system to recognize and fight certain proteins specific to cancer cells have been reported as effective, and they have been tested in research on a number of different cancers, including melanoma, non-Hodgkin's lymphoma, and prostate cancer. Each of the therapeutic vaccines currently being tested in men with advanced prostate cancer works in a slightly different fashion, but all are designed to harness the immune system's ability to fight off disease and to teach that immune system to combat prostate cancer cells. But now to the therapeutic vaccine getting all the publicity these days--- Provenge. The vaccine has been tested in the fight against metastatic prostate cancer. Provenge is composed of a person's own immune cells that have been isolated from the blood and then sensitized to prostatic acid phosphatase, which is highly expressed in over 90% of all prostate cancer tumours. These sensitized cells are then infused back into the patient. Once inside the patient, the modified cells prime the patient's immune system to recognize and destroy prostate cancer cells roaming throughout the body. An earlier phase III study of Provenge (D9901) involved 127 men with advanced prostate cancer that had spread beyond the prostate and grown resistant to hormonal therapy. Eighty-two of the men received the vaccine, while the other 45 received a placebo. Patients given the vaccine experienced an average 18% increase in survival, compared with those on a placebo. Researchers tracked patient outcomes for three years. The patients taking the vaccine survived an average of 25.9 months, compared to 22 months for those not taking the vaccine. In the terms a research scientist uses, those receiving Provenge showed a median survival benefit of 4.5 months and a three-fold improvement in survival at 36 months. And by the three-year mark, 34% of those taking the vaccine remained alive, compared with just 11% in the placebo group. The side effects were minimal: some fever and shaking for a few days at the beginning of therapy. These symptoms did not persist throughout the course of the treatment. When the FDA, against a 13-4 recommendation of its own panel of experts, refused approval for Provenge and asked for more data, another phase III study was undertaken (D9902B). That's the one reporting success this month. Detailed results from this study will be presented at the plenary session of the American Urological Association's Annual Meeting in Chicago on Tuesday, April 28. What we know now is that the randomized, double-blind, and placebo-controlled study involved 512 men from various cancer centres, men who had metastatic hormone-resistant prostate cancer. And we know Dendreon reports that Provenge "significantly prolongs survival" in these men. "It certainly sounds good, but we really need to see the details," says Otis Brawley, chief medical officer of the American Cancer Society. "I will be watching with interest and some hope." But there are always many hoops to jump through when it comes to FDA approval, especially in first-of-its-kind treatments. Perhaps, too, the flip side of the immunotherapy coin has poisoned the waters somewhat for legitimate medical innovators. There are, after all, scores of questionable clinics claiming to use this approach successfully; their websites are crammed with unlikely tales of survival and remission. (See the article " Buyer Beware: The Dark Side of Complementary and Alternative Medicine.") Men with prostate cancer must always keep in mind that immunotherapy is just emerging as a possibly viable treatment option. As of yet, no therapeutic vaccine has been approved by the FDA for use in prostate cancer or in any other cancer. But researchers are optimistic that therapeutic vaccines might soon prove to be another effective strategy to help prolong the lives of men with advanced prostate cancer. |
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