Dendreon says the patients’ white blood cells take up the antigen and within hours their surfaces bristle with fragments of the telltale molecule. The cells are then shipped back to the physician and infused into the patient. A full treatment includes three such procedures, two weeks apart.

Back inside the body, Dendreon claims the modified cells trigger the immune system to produce T cells that kill any cell sporting the PAP antigen — namely, prostate cancer cells.

In principle, that should eliminate the cancer, but Provenge does not shrink either the primary tumor or metastases.

Steven Rosenberg of the National Cancer Institute, a leading tumor immunologist, says that raises doubts over whether Provenge helps patients live longer, as the IMPACT trial reported.

“We have a lot of data that supports the idea that the product works the way it was designed to,” said Dr. Mark Frohlich, Dendreon’s chief medical officer. “We’re seeing evidence of immune-system activation. The only question is whether the T cells are killing the tumor.”

The FDA acknowledges that data supporting Provenge’s approval did not show the drug shrank tumors, but says the overall survival benefit was enough to bring it to market. Spokeswoman Rita Chapelle, citing data submitted by Dendreon, said there is a “lack of evidence of anti-tumor activity,” the reason for which “is unclear.”

SUSPICIONS OVER SURVIVAL BENEFIT

Huber’s analysis comes from data showing that men who received the placebo had very different survival times based on their age. Men older than 65 lived 17.3 months on placebo and 23 months with Provenge. Men younger than 65 lived 28 months after receiving placebo and 29 months after Provenge.

Other studies have shown that age generally does not affect how long a man survives with this form of prostate cancer, says Peter Iversen, a urologist and prostate-cancer surgeon at the University of Copenhagen and co-author of the paper with Huber.

Combining these findings led to the new paper’s conclusion: The four-month edge in median survival from Provenge for all patients was due to longer survival among older men who got the vaccine.

“There is no efficacy in the younger patients, the primary group where you would expect it,” said Huber.

Since the immune system weakens with age, an immune-based therapy should work better in younger men.

Some experts agree.

“If it was really a vaccine, you’d think younger men would show more response, since they are more immunocompetent,” said NCI’s Rosenberg.

On that basis, Huber and her co-authors, including two prostate-cancer specialists, argue the placebo used in the trial may have harmed the older men, cutting months off their lives and inadvertently making Provenge seem beneficial.

One way that could have occurred was through leukapheresis. That process removed about 90 percent of certain kinds of circulating white blood cells, according to calculations by immunologist Laura Haynes of the Trudeau Institute, a co-author of the JNCI paper.

The Provenge men got back about 32 percent of those cells, which had been stored at body temperature. The placebo men got back 12 percent, which had been incubated at near-freezing temperatures. Cold storage has been reported to kill “most, if not all, of those cells,” notes the JNCI paper. Moreover, said Haynes, “if you return dead and dying cells to older men you are likely to cause inflammation,” which can stoke the growth of cancerous cells.

Younger men were better able to replace the lost white blood cells, argued Iversen. Older men could not, resulting in early death.

“These cells are very specialized and there is research suggesting that removing them can harm older men,” he said.