Provenge: The Latest Controversy
Physicians want new treatments to work, especially for patients who no longer respond to existing treatments.
Physicians want new treatments to work, especially for patients who no longer respond to existing treatments.
It was controversial from the get go because it didn’t appear to affect disease progression and no evidence was presented to show it killed tumors. It was exorbitantly expensive, about $93,000 for a series of three infusions.
It was controversial from the get go because it didn’t appear to affect disease progression and no evidence was presented to show it killed tumors. It was exorbitantly expensive, about $93,000 for a series of three infusions.
Even that evidence of a few months extended survival is only by comparison to a placebo group of men age 65 and over. And then, the results on the placebo group over 65 did not take into account the effect of removing 26 billion mononuclear white blood cells and not replacing them.
Still, for men with late-stage prostate cancer, it seemed to provide hope that a new therapy, immunotherapy, could prolong life by a few months and, with more research, provide real help.
Dr. Catalona was concerned enough about Provenge that he wrote an article with his reactions in the Fall 2010 QUEST, My Concerns About Provenge Vaccine, (See www.drcatalona.com in archives of past QUESTs.)
In it, he said: I am concerned that information to the public has presented an unjustifiably optimistic view of vaccine therapy for prostate cancer and unrealistically suggests that Provenge will usher in a new era of cancer treatment more effective than surgery, radiation, or hormonal therapy.
In addition, from the data I have seen, I am skeptical that it will add materially to the treatment of patients with advanced-stage prostate cancer.
Now, an article published in the Journal of the National Cancer Institute (JNCI) by lead author Marie L. Huber, has reignited the controversy.
The JNCI article begins by stating: The absence of supportive data has raised the concern that the 4.1-month survival benefit [from Provenge] could be the result of a flaw in the trial design or from the chance imbalance of unmeasured prognostic variables.
We have reconsidered these trial results in light of unpublished data obtained from internal FDA documents that became available only after the approval of sipuleucel-T.
We believe that analysis of the data in their totality challenges the published interpretation of the trial results and suggests a different conclusion about the efficacy, and potentially safety, of sipuleucel-T.
Because these data have not been debated publicly, we hope that this commentary will stimulate consideration of their implications.
According to Huber, “The most logical explanation of the data I’ve seen is that Provenge treatment is harmful for older men and, at best, does nothing for men under 65. If my dad were a patient, I’d talk him through the facts before he made any treatment decisions.
“First and foremost, I’d want my dad to understand that to make Provenge, over 90% of a man’s circulating mononuclear white blood cells are harvested; 65% are lost in manufacture; and 35% are returned. Patients lose 20 billion cells whose normal role is to suppress their cancer,” Huber said.
All physicians want treatments to work. And Dr. Catalona, with his research collaborators, is working hard on research to improve treatments for prostate cancer and to discover the reasons for and the prevention of aggressive prostate cancer.
“We want and need to provide both care and hope, but false hope with possible detrimental care will do no one any good,” Dr. Catalona said.
As the JNCI article states: The safety of prostate cancer patients as well as the judicious development of beneficial immunotherapies depends on addressing the concerns raised and considering all possible interpretations of the…trial results.
