Interdisciplinary critique of sipuleucel-T as immunotherapy in castration-resistant prostate cancer.

Abstract

Sipuleucel-T was approved by the US Food and Drug Administration on April 29, 2010, as an immunotherapy for late-stage prostate cancer. To manufacture sipuleucel-T, mononuclear cells harvested from the patient are incubated with a recombinant prostatic acid phosphatase (PAP) antigen and reinfused. The manufacturer proposes that antigen-presenting cells exogenously activated by PAP induce endogenous T-cells to attack PAP-bearing prostate cancer cells. However, the lack of demonstrable tumor responses has prompted calls for scrutiny of the design of the trials in which sipuleucel-T demonstrated a 4-month survival benefit. Previously unpublished data from the sipuleucel-T trials show worse overall survival in older vs younger patients in the placebo groups, which have not been shown previously to be prognostic for survival in castration-resistant prostate cancer patients receiving chemotherapy. Because two-thirds of the cells harvested from placebo patients, but not from the sipuleucel-T arm, were frozen and not reinfused, a detrimental effect of this large repeated cell loss provides a potential alternative explanation for the survival "benefit." Patient safety depends on adequately addressing this alternative explanation for the trial results.

• Authors: Marie L Huber, Laura Haynes, Chris Parker, Peter Iversen
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 104 Issue 4 Pg. 273-9 (Feb 22 2012) ISSN: 1460-2105 [Electronic] United States
• PMID: 22232132 (Publication Type: Journal Article)

Chemical References

• Cancer Vaccines
• Tissue Extracts
• sipuleucel-T
• Acid Phosphatase
• prostatic acid phosphatase
• Protein Tyrosine Phosphatases

Topics

• Acid Phosphatase
• Age Factors
• Aged
• Aged, 80 and over
• Aging
• Cancer Vaccines (adverse effects, therapeutic use)
• Clinical Trials as Topic
• Humans
• Immunotherapy (adverse effects, methods)
• Male
• Middle Aged
• Neoplasms, Hormone-Dependent (drug therapy, immunology, mortality)
• Patient Selection
• Prognosis
• Prostatic Neoplasms (drug therapy, immunology, mortality)
• Protein Tyrosine Phosphatases (metabolism)
• Research Design
• Survival Analysis
• Tissue Extracts (adverse effects, therapeutic use)