The JNCI Paper: Peer-reviewed Publication of the Alternative Explanation

Interdisciplinary Critique of Sipuleucel-T as Immunotherapy in Castration-Resistant Prostate Cancer

Huber ML, Haynes L, Parker C, Iversen P.           Access Free Article         Journal of the National Cancer Institute  Feb 22, 2012

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 Previously unpublished data from the sipuleucel-T trials show worse overall survival in older vs younger patients in the placebo groups, which have not been shown previously to be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.


Chris Parker, MD, MRCP, FRCR

Senior Lecturer and Honorary Consultant in Clinical Oncology and Prostate Cancer Translational Research at The Institute of Cancer Research and The Royal Marsden, UK.

Clinical Team: Urology Unit at The Royal Marsden

Hospital website: link

Research Interests:

  • active surveillance of low-risk disease
  • the role of post-operative adjuvant therapy
  • the role of bone-targeted therapy for advanced disease

Lab website: link

Dr Parker is a member of the UK Department of Health Prostate Cancer Advisory Group.

Peter Iversen, MD

Professor of Urology at Rigshospitalet, Copenhagen, Denmark, since 2006

Webpage: link

  • Professor Iversen has special interest in the research and treatment of prostate cancer and has been the Chief Coordinator of DAPROCA (Danish Prostatic Cancer Group). He has been active in several international groups and continues to be a member of the Scandinavian Prostatic Cancer Group, where he served as the Chairman from 1996-1999.
  • He has authored more than 200 peer-reviewed publications/ textbooks chapters
  • He has served as a Principal Investigator on several large multicenter prostate cancer trials and has given more than 500 presentations at major meetings- mostly on prostate cancer related topics.

Laura Haynes, Ph.D.

Faculty at the Trudeau Institute, Saranac Lake, NY

Research Interests:

  • The Impact of Aging on Immune Responses
  • Examination of Vaccine Efficacy and Protection from Infection

Lab website : link

Dr Haynes is also an Adjunct Associate Professor of Medicine, University of Vermont : link