Sipuleucel-T prolonged PSA doubling time in patients with androgen-dependent prostate cancer.


CHICAGO—Sipuleucel-T (Provenge), an experimental immunotherapy, is safe and potentially beneficial in men with androgen-dependent prostate cancer (ADPC), study findings suggest.

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The treatment, which was compared with placebo, prolonged patients’ PSA doubling time (PSADT), but did not significantly delay the time it took for a patient’s PSA level to rise to 3 ng/mL or greater, according to the study’s principal conclusions. Researchers observed a trend toward a delay in the development of metastatic disease.


The ongoing trial, known as P-11, is a double-blind, multi-center, randomized study involving 176 men with ADPC who had prostatectomies and then experienced cancer recurrence as indicated by rising PSA levels. After three months of hormone therapy, 117 men received sipuleucel-T and 59 received placebo.


The median time to biochemical failure was 18 months for sipuleu-cel-T and 15.4 months for placebo. The rate of PSA rise was 30% to 48% slower in the patients receiving sipuleucel-T, investigators reported. Sipuleucel-T had a favorable safety profile, researchers said. Fatigue, chills, and fever were the adverse effects seen more commonly in sipuleucel-T recipients than in placebo patients.


After patients’ PSA levels reached 3.0 ng/mL, they became eligible for one booster infusion of either sipuleucel-T or placebo, depending on the treatment arm to which they were randomized.


The investigators monitored immune response in a subset of sipuleucel-T and placebo treated patients and found that the immune response elicited by sipuleucel-T was durable and still strong just prior to booster infusion. The booster infusion occurred an average of 21 months following initial treatment. Following a booster infusion of sipuleucel-T, patients demonstrated an immune response 10-fold to 100-fold higher than in placebo patients.


“What we really need to know is if we can delay metastases and whether we delay death from prostate cancer.  We are still conducting this study so we don’t have those answers yet,” said study investigator Tomasz Beer, MD, director of the prostate cancer research program and associate professor of medicine at the Oregon Health & Science University Cancer Institute.


“The good news is that the treatment is well tolerated and so now there is additional safety data.”

Manufactured by Dendreon Corporation, sipuleucel-T is a cellular immunotherapy that targets the prostate-specific acid phosphatase (PAP) antigen. Sipuleucel-T is prepared by exposing each patient’s peripheral blood mononuclear cells to a fusion protein that includes the PAP target and the immune modulator GM-CSF.


Study findings were presented here at the American Society of Clinical Oncology annual meeting.


An FDA advisory committee recently endorsed its safety and effectiveness for use in men with meta-static, androgen-independent pros-tate cancer, a different and more advanced patient population than the men 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 try to train the body’s own immune system to fight prostate cancer.


“Right now, none of our data is showing that this therapy is something that we can take to our patients definitively. The issues of metastases, quality of life, and overall duration of survival are yet to be determined,” Dr. Beer said. “Hopefully, we will be able to know something about those issues over the next several years.”