Sipuleucel-T: a vaccine for metastatic, asymptomatic, androgen-independent prostate cancer.
OBJECTIVE
To review the design, efficacy, safety, dosing, therapeutic, and pharmacoeconomic considerations of sipuleucel-T, an investigational, autologous, dendritic, cell-based prostate cancer vaccine.


METHODS
English-language literature searches of MEDLINE (1966-September 2007) and the Cochrane Database (2007, Issue 3) were performed using the terms sipuleucel-T, APC8015, and prostate cancer vaccine. Other data sources were identified from bibliographies of selected articles and from press releases.


METHODS
All published articles or abstracts on human studies of sipuleucel-T for androgen-independent prostate cancer (AIPC) were reviewed for inclusion. Manufacturer Web sites, Food and Drug Administration (FDA) documents, and the clinical trials registry were used to obtain information regarding ongoing clinical trials.


RESULTS
AIPC is an incurable disease with a median survival rate of 18-20 months. Docetaxel-based chemotherapy is currently the only FDA-approved treatment for AIPC with a survival benefit (2.4 mo). Sipuleucel-T is a novel active cellular immunotherapy under investigation for the treatment of metastatic, asymptomatic AIPC. In clinical trials, the primary endpoint of time to disease progression was not met; however, an underpowered analysis of data suggests that sipuleucel-T prolongs survival by a median of 4.5 months compared with placebo. Sipuleucel-T has been relatively well tolerated, although a possible increased risk of cerebrovascular events may exist. In May 2007, the FDA did not approve the biologics license application for sipuleucel-T since the primary endpoint of the Phase 3 trials was not met. However, its approval will be reconsidered by the FDA once interim survival results from an ongoing Phase 3 trial, IMPACT, are determined. These data are anticipated to be released in the fourth quarter of 2008.


CONCLUSIONS
Metastatic AIPC is an incurable disease that currently has limited treatment options. Approval of sipuleucel-T hinges on results from the IMPACT trial. If improved survival is shown, sipuleucel-T may become the first approved active cellular immunotherapy for treating metastatic, asymptomatic AIPC.
Patel
Punam H
PH
Drug Information Services, Virginia Commonwealth University Health System/Medical College of Virginia Hospitals, Richmond, VA 23298, USA.
Kockler
Denise R
DR
D019496:Cancer Vaccines / Q000009:adverse effects / Q000191:economics / Q000494:pharmacology*; D018849:Controlled Clinical Trials as Topic; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000276:immunology; D016019:Survival Analysis; D014020:Tissue Extracts / Q000009:adverse effects / Q000191:economics / Q000494:pharmacology*
D019496:Cancer Vaccines; D014020:Tissue Extracts; C511774:sipuleucel-T