Provenge Fights Prostate Cancer

By Dr. Ralph Moss

Prostate cancer is one of the most common cancers. Each year in the US, around 230,000 men are newly diagnosed with prostate cancer and 30,000 die of the disease.

A new form of immune therapy has shown a significant survival benefit in men who have metastatic androgen-independent prostate cancer, when compared to patients receiving placebo.

The treatment is called Provenge (APC8015) and is manufactured by Dendreon Corp. of Seattle. Provenge is called a vaccine, but unlike most vaccines, it is used not to prevent illness but to treat an already existing condition. The vaccine combines a protein that is found in most prostate cancer cells with a substance that helps the immune system recognize the cancer as a threat. In clinical trials, Provenge was well tolerated: the most common adverse events that were reported were fever and chills lasting for one to two days.

The vaccine is autologous in nature. That is, it is produced from the patient's own cells and must be custom made for each patient individually. First, patients have their blood run through a machine for two or three hours in order to extract certain immune system cells, called antigen presenting cells (APCs). These cells are then mixed with a protein called prostatic acid phosphatase (PAP) that is commonly found on most prostate tumors. The PAP is fused with another immune-stimulating substance called GM-CSF. The mixture is then returned to the patient in a one-hour infusion. This process is repeated three times over the course of a month. The basic idea is to alert the immune system that cells containing prostatic acid phosphatase, (i.e., prostate cancer cells) should now be attacked as if they were a foreign invader.

Antigen presenting cells (APCs), a class of cells that includes dendritic cells and macrophages, are of major importance in immunotherapy. They are distributed throughout the skin, respiratory tract, and gastrointestinal tract. APCs serve two major functions: they capture and process cell-surface markers, or antigens, for presentation to the T class of lymphocytes. And they also produce signals that are required for the proliferation and differentiation of those lymphocytes.

For several years, dendritic cell vaccines have been offered at CAM-oriented clinics in Mexico, the Caribbean and northern Europe, but have not been available in the US outside the strict confines of clinical trials.

In the latest study, men who were treated with Provenge survived on average 26 months, compared to 21.4 months for those who received only a placebo injection. This may not seem like much, but in fact this 4.5-month median survival benefit is said to be the longest ever reported from a Phase III study in advanced prostate cancer. It is better than the roughly 2.5-month benefit that was shown in clinical trials of Taxotere, a drug from Sanofi-Aventis. Taxotere is presently one of only a few approved forms of chemotherapy for patients whose cancer has spread beyond the prostate gland and is no longer responsive to hormonal therapy (the others are estramustine and mitoxantrone).

What is more, at three years, 28 of the 82 men who received Provenge were still alive, compared to only 4 of 45 patients in the placebo group. Provenge is now considered to have a shot at becoming the first anticancer therapy vaccine to be approved by the Food and Drug Administration (FDA). Approval will probably depend on the results of a larger study, currently underway, which should be reported by the end of 2005.

"This is provocative, it is promising. We now need to confirm this with an independent study," said Dr. Philip Kantoff, a Harvard Medical School professor who heads prostate cancer treatment at the Dana-Farber Cancer Institute in Boston. He was not involved in latest company-supported study.

The authors of the study emphasized the fact that the men who received the vaccine were actually living longer. However, paradoxically, the study did not achieve its primary goal of delaying the progression of the men's disease. This apparent contradiction has caused some controversy. Some critics contend that "time to progression" is the standard measurement of benefit and should have been extended if the vaccine were truly helping men live longer. Dr. Kantoff described his attitude as "skeptical."

But according to Dr. Stephen Small, MD, professor of medicine and urology at the University of California, San Francisco, who led the Phase III study, "Time to progression is interesting, but it isn't the gold standard. The gold standard is survival. We've improved survival....A therapy that prolongs life yet avoids the side-effects of other therapeutic approaches is clearly attractive to patients and physicians alike."

Dr. Small pointed out that the time to progression was not the right measure to use for judging cancer vaccines because cancer can worsen before the immune system starts to fight it. He said that Provenge improved the survival of all patients, not just those who had less aggressive cancers.

"The survival benefit seen with Provenge is the largest ever reported in this patient population with any therapy," said Dr. Small. "This survival benefit, combined with a favorable safety profile, has the potential to provide an important new treatment option for prostate cancer patients."

The results were reported on February 19, 2005 at the Multidisciplinary Prostate Cancer Symposium in Orlando, FL. Dendreon's stock price, which had been as high as $16 per share, sank in January when it was announced that the drug was failing to attain its primary objective of delaying the time to progression. When word leaked out about the survival advantage, its stock spike upward by 15 percent. However, within a week it had returned to its recent $6-7 range. This may have been the result of negative statements coming from others in the cancer research community.

According to the Seattle Times, "the treatment has numerous skeptics." These include Patrick Walsh, MD, a Johns Hopkins University urologist and a well-known prostate-cancer surgeon, who said the study was too small to allow definitive conclusions. He said it was unknown what other therapies patients may have had during the three-year follow-up period, which may have made a difference.

"The numbers here are just too small to make this a big deal," said Walsh. Dr. Howard West, an oncologist at Swedish Medical Center, Seattle, said the study would be a stronger statement if the survival edge was seen across a larger number of patients. Still, he called the finding "extremely intriguing."

In addition to Provenge, the company has another vaccine in development. This is called APC8024 and targets HER-2/neu positive cancers, including those of the breast, ovaries, colon and lung. is directed by Ralph W. Moss, Ph.D. Dr. Moss is the author of eleven acclaimed books including Antioxidants Against Cancer, Herbs Against Cancer, Questioning Chemotherapy, and Cancer Therapy. He consults for thousands of clients through his Moss Reports service. The Moss Reports specializes in educating cancer patients about the most promising alternative treatments for their condition.

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Marchione, Marilynn. Treatment for prostate cancer offers promise. Vaccine approach seeks to fight tumors. Associated Press, Feb. 17, 2005.

Pollack, Andrew. Prostate cancer vaccine shows promise in a trial. New York Times, Feb. 17, 2005.


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