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 Previously unpublished data from the sipuleucel-T trials show worse overall survival in older vs younger patients in the placebo groups, which have not been shown previously to be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.
Written by:
Huber ML, Haynes L, Parker C, Iversen P. Are you the author?
Trudeau Institute, Saranac Lake, NY; Academic Urology Unit, The Royal Marsden NHS Foundation Trust, UK; Department of Urology, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark.
Reference: J Natl Cancer Inst. 2012 Jan 30. Epub ahead of print.
doi: 10.1093/jnci/djr514
PubMed Abstract
PMID: 22232132
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