Interdisciplinary critique of sipuleucel-T as immunotherapy in castration-resistant prostate cancer.
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 Previously unpublished data from the sipuleucel-T trials show worse overall survival in older vs younger patients in the placebo groups, which have not been shown previously to be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.
Marie L
ML
Huber
Laura
L
Haynes
Chris
C
Parker
Peter
P
Iversen
D000135:Acid Phosphatase; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D019496:Cancer Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D018579:Patient Selection; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D012107:Research Design; D016019:Survival Analysis; D014020:Tissue Extracts / Q000009:adverse effects / Q000627:therapeutic use*
D019496:Cancer Vaccines; D014020:Tissue Extracts; C511774:sipuleucel-T; D000135:Acid Phosphatase; C428439:prostatic acid phosphatase; D017027:Protein Tyrosine Phosphatases