Randomized trial of autologous cellular immunotherapy with sipuleucel-T in androgen-dependent prostate cancer.

Abstract

PURPOSE:

Sipuleucel-T, an autologous cellular immunotherapy, was investigated in a randomized, double-blind, controlled trial to determine its biologic activity in androgen-dependent prostate cancer (ADPC).

EXPERIMENTAL DESIGN:

Patients with prostate cancer detectable by serum prostate-specific antigen (PSA) following radical prostatectomy received 3 to 4 months of androgen suppression therapy, and were then randomized (2:1) to receive sipuleucel-T (n = 117) or control (n = 59). The primary endpoint was time to biochemical failure (BF) defined as serum PSA ≥ 3.0 ng/mL. PSA doubling time (PSADT), time to distant failure, immune response, and safety were also evaluated.

RESULTS:

Median time to BF was 18.0 months for sipuleucel-T and 15.4 months for control (HR = 0.936, P = 0.737). Sipuleucel-T patients had a 48% increase in PSADT following testosterone recovery (155 vs. 105 days, P = 0.038). With only 16% of patients having developed distant failure, the treatment effect favored sipuleucel-T (HR = 0.728, P = 0.421). The most frequent adverse events in sipuleucel-T patients were fatigue, chills, and pyrexia. Immune responses to the immunizing antigen were greater in sipuleucel-T patients at Weeks 4 and 13 (P < 0.001, all) and were sustained prior to boosting as measured in a subset of patients a median of 22.6 months (range: 14.3-67.3 months) following randomization.

CONCLUSIONS:

No significant difference in time to BF could be shown. The finding of increased PSADT in the sipuleucel-T arm is consistent with its biologic activity in ADPC. Long-term follow-up will be necessary to determine if clinically important events, such as distant failure, are affected by therapy. Treatment was generally well tolerated.

• Authors: Tomasz M Beer, Guy T Bernstein, John M Corman, L Michael Glode, Simon J Hall, Wayne L Poll, Paul F Schellhammer, Lori A Jones, Yi Xu, Jelle W Kylstra, Mark W Frohlich
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 17 Issue 13 Pg. 4558-67 (Jul 01 2011) ISSN: 1557-3265 [Electronic] United States
• PMID: 21558406 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Androgens
• Cancer Vaccines
• Tissue Extracts
• Intercellular Adhesion Molecule-1
• sipuleucel-T
• Prostate-Specific Antigen

Topics

• Aged
• Androgens (metabolism)
• Cancer Vaccines (adverse effects, therapeutic use)
• Humans
• Immunotherapy, Adoptive (adverse effects)
• Intercellular Adhesion Molecule-1 (immunology, metabolism)
• Male
• Middle Aged
• Prostate-Specific Antigen (metabolism)
• Prostatic Neoplasms (immunology, therapy)
• Tissue Extracts (adverse effects, therapeutic use)
• Treatment Outcome
• Up-Regulation (immunology)