Provenge prostate cancer vaccine linked to longer survival for asymptomatic hormone refractory stage

June 28, 2006 - A University of California, San Francisco study has found that men with advanced, often untreatable prostate cancer who received a therapeutic cancer vaccine went on to survive longer than those receiving a placebo.

Study findings showed the vaccine group lived up to an average of four-and-a-half months longer and had a greater than three-fold increase in survival at 36 months when compared to patients in the placebo group.

The study is reported in the July 1, 2006 issue of the Journal of Clinical Oncology [abstract]. The double-blind, placebo-controlled phase III clinical trial was conducted to test the efficacy of the vaccine, called Provenge (sipuleucel-T), in delaying disease progression and prolonging survival in patients with asymptomatic metastatic hormone refractory prostate cancer (HRPC).

Study results showed that the vaccine was well-tolerated by participants. The most common reported side effects such as fever and chills were typically mild.

Led by Eric J. Small, MD, UCSF professor of medicine and urology, the study was conducted in collaboration with 19 institutions in the United States and funded by the Dendreon Corporation, a biotechnology company that developed the vaccine.

"This trial is an important milestone in the development of new treatments for prostate cancer patients," said Small. "The potential survival benefit that was observed may offer important benefits to patients and would represent the first time that immunotherapy has provided a survival advantage in prostate cancer."

Provenge is an investigational immunotherapy vaccine designed to stimulate T-cell immunity to prostatic acid phosphatase, an antigen found in about 95 percent of prostate cancers but not in non-prostate tissue.

A total of 127 patients with asymptomatic metastatic HRPC received three transfusions of Provenge or placebo every two weeks. Of this group, 115 patients had progressive disease at the time of data analysis and all patients were followed for survival for 36 months.

Asymptomatic metastatic hormone refractory prostate cancer (HRPC) is a relatively advanced stage of the disease. HRPC develops if androgen deprivation treatments fail following either late diagnosis or failure of timely primary treatments (surgery, brachytherapy or external beam radiation). Treatment options are limited for patients at this stage of the disease except for chemotherapy.

The study showed that the median overall survival was 25.9 months for Provenge-treated patients and 21.4 months for placebo-treated patients. After three years, survival was 34 percent for those treated with the vaccine compared to 11 percent for those taking the placebo.

The clinical trial did not meet its primary endpoint of demonstrating a statistically significant difference in progression of the disease from diagnosis, according to Small.

"We found that the time to disease progression for sipuleucel-T was 11.7 weeks compared to 10.0 weeks for placebo," he said. "This shows the difficulties in using the worsening of the disease as an intermediate marker for overall survival of patients treated with immunotherapy," he said. "The study however, suggests that sipuleucel-T may provide a survival advantage to asymptomatic HRPC patients."

Many of the phase I and II clinical trials of the vaccine were also undertaken at UCSF and led by Small. He first presented results from the phase III trial at the 2005 meeting of the American Society of Clinical Oncology.

Dendreon Corporation, based in Seattle, Washington, hopes to market the Provenge product commercially in the coming year. Co-authors of the study are Paul F. Schelhammer, Eastern Virginia Medical School, Norfolk, VA; Celestia S. Higano, University of Washington; Charles H. Redfern, Sharp Healthcare, San Diego; John J. Nemunaitis, Mary Crowley Medical Research Center, Dallas; and Frank H. Valone, Suleman S. Verjee, Lori A. Jones and Robert M. Hershberg, Dendreon Corporation. UCSF is a leading university that consistently defines health care worldwide by conducting advanced biomedical research, educating graduate students in the life sciences, and providing complex patient care.