Provenge in 2012

BY MARK SCHOLZ, MD

Doctors finally seem to be comfortable with starting Provenge, a recently FDA approved immune therapy for prostate cancer.  Dendreon, the manufacturer of Provenge, just reported a sharp uptick in their quarterly financials, indicating that the use of Provenge is increasing as doctors increase the amount of the drug they order.

Although, Provenge has been on the market for 18 months but the medical community was slower to embrace this new treatment than was expected.  It seems that it has taken time for doctors to make peace with the fact that Provenge extends life, even though there is no lowering of PSA and very few side effects.

At Prostate Oncology Specialists, we recently completed an in-house review of the first 50 men treated with Provenge, I’ll jump right to the simple and somewhat mundane conclusion or our analysis: Provenge is relatively easy to give and side effects are uncommon.

Historically, the effectiveness of cancer treatments—like chemotherapy for example—has been closely associated with notable side effects. Side effects were often equated with effectiveness.  Even some of the new immune treatments, like Ipilimumab for example, usually have side effects. It’s ironic that patients receiving Ipilimumab on investigational trials are actually comforted when they get side effects—it confirms that they are not getting a placebo.

It’s also ironic that while doctors look for PSA decline as a measure of success, PSA has been rejected by the FDA as a method for measuring the effectiveness of drugs. The FDA demands a survival endpoint rather than changes in PSA.  (Personally, I think the FDA is crazy. I think that both PSA and survival endpoints are valid.)

Nevertheless, doctors and patients alike are confused. Their seemingly logical question is, “How can someone’s life be extended without PSA dropping?”  My explanation is as follows: When Provenge strengthens the immune system, is slows the rate of cancer growth.  Using the rise in PSA as analogous for cancer growth, Provenge slows the rate of PSA rise.

I am very comfortable with the idea that effective immune therapy slows cancer growth rather than reversing it.  This phenomenon of slowing the rate of PSA rise is exactly what we reported to the American Society of Clinical Oncology in 2010 when we presented our results with three medicines with immune activity, Leukine, Low-dose cytoxan and Celebrex.  The combination of these three agents caused substantial slowing in the rate of PSA rise.

Since Provenge is so well tolerated, the next logical step is to evaluate Provenge in combination with other immunologically active treatments.  MD Anderson is ramping up to do a trial of Provenge with full-dose Ipilimumab.  At Prostate Oncology Specialists we look forward to working with treatment options such as Provenge and Ipilimumab for our patients. Hopefully the net result will be greater than the sum of the parts.