Findings from study of immunotherapy vaccine in prostate cancer patients

Data from an ongoing study designed to explore the biologic and clinical activity of cancer immunotherapy sipuleucel-T, or Provenge, in patients with early stage recurrent prostate cancer who have a rising serum prostate specific antigen (PSA) level, but who have not yet developed metastatic disease will be presented by Oregon Health & Science University Cancer Institute researchers.

The study showed that sipuleucel-T did not significantly delay the time it took for a patient's PSA to reach a value of 3 ng/ml, the primary endpoint of the study, but it did show a prolongation in prostate-specific antigen doubling time (PSADT). In addition, there was a trend observed in slowing the time to metastatic disease for patients who received sipuleucel-T compared with those who received placebo, but this early trend did not reach statistical significance. The findings were presented at the 43rd Annual Meeting of the American Society of Clinical Oncologists (ASCO) in Chicago.

"While there was no delay in the time to PSA recurrence, we did observe a slowing in the rate of rise of serum PSA in exploratory analyses. Additional follow-up is needed to determine if this effect on PSA will translate into patient benefits," said Tomasz Beer, M.D., lead investigator, director of the Prostate Cancer Research program at the OHSU Cancer Institute; and associate professor of medicine, (hematology/medical oncology) OHSU School of Medicine.

The ongoing trial, known as P-11, is a double-blind, multi-center, randomized, placebo-controlled study involving 176 men, all of whom had prostatectomies and then had recurrent cancer as detected by a rise in the serum tumor marker, PSA. After three months of hormone therapy, 117 men received sipuleucel-T and 59 received placebo.

Sipuleucel-T was found to have a favorable safety profile. The most common side effects seen more commonly in sipuleucel-T-treated patients were fatigue, chills and fever.

The effects of sipuleucel-T on prostate cancer progression were analyzed in several ways using measurements of serum PSA. The primary analysis focused on time until the PSA reaches 3.0 ng/ml. Although there was a trend, the immunotherapy did not significantly delay cancer progression by this measure. However, investigators found the rate at which PSA was rising was 30 percent to 48 percent slower in patients who received sipuleucel-T compared to those who received placebo.

After patients' PSAs reached 3.0 ng/ml, they became eligible for one booster infusion of either sipuleucel-T or placebo in accordance with the treatment arm to which they were randomized. An immune monitoring protocol performed in a subset of patients demonstrated that the immune response elicited by sipuleucel-T was long-lived and still strong just prior to the booster infusion, which occurred an average of 21 months following initial treatment with the immune stimulating agent. Following a booster infusion of sipuleucel-T, patients demonstrated an immune response approximately 10- to 100-fold higher than measured in placebo arm patients.

Sipuleucel-T is manufactured by Dendreon Corporation. An FDA advisory committee recently supported the safety and effectiveness for the use of sipuleucel-T in men with metastatic, androgen- independent prostate cancer (a different and more advanced patient population than those observed in this study). The FDA has delayed the approval of sipuleucel-T until more clinical data are available from an ongoing study, known as IMPACT. If approved, sipuleucel-T would be the first FDA-approved treatment designed to train the body's own immune system to fight cancer.

Prostate cancer is the most common nonskin cancer in the United States and the third most common cancer worldwide. More than 1 million men in the United States have prostate cancer, with an estimated 218,890 new cases expected to be diagnosed in 2007, and more than 27,000 men expected to die this year from the disease.