Advisory Panel Recommends New Drug to Fight Prostate Cancer

Chicago Tribune

03-30-07

CHICAGO - A government panel gave the go-ahead Thursday for the first in a new class of anti-cancer drugs: an experimental agent that works by mobilizing the body's natural immune system to fight prostate cancer.

If the federal Food and Drug Administration accepts the recommendation of its advisory committee, as it usually does, the drug will become the first therapeutic cancer vaccine to win regulatory approval.

Unlike vaccines that prevent diseases such as polio and measles-or, in the case of the HPV vaccine, cervical cancer-therapeutic vaccines are meant to treat an existing disease.

The new agent, known by the trade name Provenge, has been tested only in late-stage prostate cancer patients and added only a few months to their lives. But scientists hailed the drug as a step in the right direction because it could be the first of many such vaccines, also called active cellular immunotherapies.

"This is an exciting time in prostate cancer," said Dr. Edwin Posadas of the University of Chicago, an oncologist who specializes in the disease. "We're not there yet, but we are definitely making progress.

"Ten years ago, if you had (advanced) prostate cancer, we could do nothing but treat the pain. Now we have effective chemotherapy and a growing repertoire of agents that look like they might have an impact on the disease."

Part of the excitement is due to the fact that Provenge demonstrates what researchers call "proof of principle"-evidence that the immune system can recognize and fight prostate cancer. The FDA's advisory committee voted 13-4 Thursday that the drug was effective.

Doctors would also be thrilled to have a targeted drug that can kill cancer cells gently, without causing debilitating side effects. The committee voted unanimously that it was safe.

The most common side effects of Provenge are flu-like fever and chills. It doesn't cause the hair loss or nerve damage that are common with chemotherapy, nor the hot flashes or mood swings of hormonal treatment. That's important, experts noted, because men are living longer with prostate cancer and doctors worry about their quality of life.

Prostate cancer is the most common malignancy in U.S. men, other than common skin cancers. More than a million men are living with the disease. The American Cancer Society estimates that nearly 220,000 new cases of prostate cancer will be diagnosed this year and more than 27,000 men will die of the illness.

Scientists have been working for decades-mostly without success-to find ways of getting the immune system to recognize tumor cells as the enemy and attack them the same way a preventive vaccine fights off infections.

Unlike invading viruses and bacteria, however, tumors are composed of the body's own cells, multiplied out of control. Although tumors carry molecular markers that could provoke an immune response, they aren't always visible to the immune system. Or, if they are spotted, they aren't perceived as alien and attacked.

So researchers have been forced to try increasingly sophisticated techniques to train the immune system to spot and fight tumor cells.

Provenge uses dendritic cells, special white blood cells that are uniquely able to attract the attention of other types of cells in the immune system, such as T cells.

Doctors harvest dendritic cells from the patient's blood and send them to a lab at Dendreon Corp., the company that developed Provenge. There the cells are mixed with a booster and a target molecule, or antigen, that's abundant on the surface of nearly all prostate cancer cells but not on normal cells.

The vaccine is then injected back into the patient, in three infusions that constitute the entire course of treatment. The dendritic cells present the prostate antigen to the T cells, showing them which molecular targets to attack. Then the T cells-which have long memories-search out and destroy diseased cells carrying the antigen.

Dr. Robert Flanigan, a urologic oncologist at Loyola University Medical Center who is involved in the clinical trials of Provenge, said the results of the trials were encouraging.

"This is a reasonable drug to give," he said, "because it's well tolerated."

Another investigator, Dr. Dennis Pessis of Rush University Medical Center, noted that the drug likely will be approved only for patients with advanced prostate cancer that has spread to other organs and has stopped responding to routine medications.

But he said he expected that, once the drug is on the market, some doctors will prescribe it "off-label" for less-advanced patients.

"Patients are going to request it (even though) I assume insurance would not cover it," said Pessis, adding that he expects the vaccine to be expensive.

The FDA's final ruling is expected by May 15.

Two prophylactic vaccines already have been approved to prevent viruses that can cause cancer-one for hepatitis B, which can lead to liver cancer, and the other for human papillomavirus, which can cause cervical cancer.

A number of other therapeutic cancer vaccines are in late-stage clinical trials and could come to market in the next few years. They include vaccines to treat lymphoma, kidney cancer, melanoma and multiple myeloma.

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