The role of sipuleucel-T in therapy for castration-resistant prostate cancer: a critical analysis of the literature.
BACKGROUND
Sipuleucel-T, an autologous antigen-presenting cell vaccine loaded with prostate acid phosphatase conjugated with granulocyte-macrophage colony-stimulating factor (GM-CSF), yielded a survival advantage in men with metastatic castration-resistant prostate cancer (mCRPC).


OBJECTIVE
Critically analyze the role of sipuleucel-T in therapy for mCRPC.


METHODS
A systematic review of the literature was performed in June 2011 using Medline and an abstract search of major cancer conferences. The search strategy included the terms sipuleucel-T, APC-8015, castration-resistant, prostate cancer, and immunotherapy.


RESULTS
The era of targeted immunotherapy was initiated with the regulatory approval in 2010 of sipuleucel-T for asymptomatic and minimally symptomatic mCRPC. The median survival was prolonged by 4.1 mo (25.8 vs 21.7 mo; hazard ratio: 0.78; 95% confidence interval, 0.61-0.98; p=0.03), coupled with an improvement in 3-yr survival (31.7% vs 23.0%). Outcomes were characterized by the lack of tumor regression or delay in progression. Further development is proceeding in earlier stages of prostate cancer and in the context of a host of emerging agents.


CONCLUSIONS
The addition of sipuleucel-T, an immunotherapeutic agent, to the armamentarium represents a paradigm shift in therapy for mCRPC. The rational combination and proper sequencing of sipuleucel-T with other newly approved agents (abiraterone acetate, cabazitaxel) and emerging agents (MDV3100, TAK-700, ipilimumab) will be important to evaluate.
Texas Oncology, Houston, TX, USA. guru.sonpavde@usoncology.com
Guru
G
Sonpavde
Giuseppe
G
Di Lorenzo
Celestia S
CS
Higano
Philip W
PW
Kantoff
Ravi
R
Madan
Neal D
ND
Shore
D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D019317:Evidence-Based Medicine; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D013997:Time Factors; D014020:Tissue Extracts / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D019496:Cancer Vaccines; D014020:Tissue Extracts; C511774:sipuleucel-T