Hormone Refractory Prostate Cancer: Focus on Sipuleucel-T

2009 ◽  
Vol 1 ◽  
pp. CMT.S1084
Author(s):  
Christian Doehn ◽  
Martin Sommerauer ◽  
Xiyuan Guo ◽  
Ingo Kausch ◽  
Dieter Jocham
Keyword(s):  
Prostate Cancer ◽  
Prostatic Acid Phosphatase ◽  
The United States ◽  
Phase Iii ◽  
Fusion Product ◽  
Hormone Refractory Prostate Cancer ◽  
Clinical Responses ◽  
Hormone Refractory ◽  
Macrophage Colony ◽  
Antigen Presenting

Sipuleucel-T is a vaccine based on autologous antigen presenting cells that are loaded with an antigen-cytokine (prostatic acid phosphatase and granulocyte-macrophage colony-stimulating factor) fusion product. Sipuleucel-T is given intravenous in weeks 0, 2, and 4. Within phase I–III trials, patients with metastatic hormone-refractory prostate cancer have been treated. In these trials an activation of the immune system could be demonstrated. Also, some clinical responses could be documented. Moreover, in a placebo-controlled phase III trial including 127 patients a statistical significantly prolongation of survival was achieved. Side effects from the vaccine are rather mild and included fever, myalgia, fatigue and others. The Food and Drug Administration in the United States requested further data before possible approval of sipuleucel-T.

Placebo-Controlled Phase III Trial of Immunologic Therapy with Sipuleucel-T (APC8015) in Patients with Metastatic, Asymptomatic Hormone Refractory Prostate Cancer

2006 ◽  
Vol 24 (19) ◽  
pp. 3089-3094 ◽  
Author(s):  
Eric J. Small ◽  
Paul F. Schellhammer ◽  
Celestia S. Higano ◽  
Charles H. Redfern ◽  
John J. Nemunaitis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
T Cell ◽  
Disease Progression ◽  
Statistical Significance ◽  
Prostatic Acid Phosphatase ◽  
Phase Iii ◽  
Controlled Study ◽  
Hormone Refractory Prostate Cancer ◽  
Cell Immunity ◽  
Hormone Refractory

Purpose Sipuleucel-T (APC8015) is an investigational immunotherapy product designed to stimulate T-cell immunity against prostatic acid phosphatase. A phase III study was undertaken to evaluate the safety and efficacy of sipuleucel-T in a placebo-controlled study. Patients and Methods A total of 127 patients with asymptomatic metastatic hormone refractory prostate cancer (HRPC) were randomly assigned in a 2:1 ratio to receive three infusions of sipuleucel-T (n = 82) or placebo (n = 45) every 2 weeks. On disease progression, placebo patients could receive APC8015F, a product made with frozen leukapheresis cells. Results Of the 127 patients, 115 patients had progressive disease at the time of data analysis, and all patients were followed for survival for 36 months. The median for time to disease progression (TTP) for sipuleucel-T was 11.7 weeks compared with 10.0 weeks for placebo (P = .052, log-rank; hazard ratio [HR], 1.45; 95%CI, 0.99 to 2.11). Median survival was 25.9 months for sipuleucel-T and 21.4 months for placebo (P = .01, log-rank; HR, 1.70; 95%CI, 1.13 to 2.56). Treatment remained a strong independent predictor of overall survival after adjusting for prognostic factors using a Cox multivariable regression model (P = .002, Wald test; HR, 2.12; 95%CI, 1.31 to 3.44). The median ratio of T-cell stimulation at 8 weeks to pretreatment was eight-fold higher in sipuleucel-T-treated patients (16.9 v 1.99; P < .001). Sipuleucel-T therapy was well tolerated. Conclusion While the improvement in the primary end point TTP did not achieve statistical significance, this study suggests that sipuleucel-T may provide a survival advantage to asymptomatic HRPC patients. Supportive studies are underway.

Prostate-specific antigen as a measure of disease outcome in metastatic hormone-refractory prostate cancer.

1993 ◽  
Vol 11 (4) ◽  
pp. 607-615 ◽  
Author(s):  
W K Kelly ◽  
H I Scher ◽  
M Mazumdar ◽  
V Vlamis ◽  
M Schwartz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Specific Antigen ◽  
Phase Iii ◽  
Cancer Center ◽  
Hormone Refractory Prostate Cancer ◽  
Data Set ◽  
Hormone Refractory

PURPOSE To evaluate the prognostic significance of pretreatment parameters and posttherapy declines in prostate-specific antigen (PSA) in relation to the survival of patients with hormone-refractory prostate cancer. PATIENTS AND METHODS One hundred ten assessable patients treated on seven sequential protocols at Memorial Sloan-Kettering Cancer Center (MSKCC) for hormone-refractory prostate cancer were evaluated for 29 different pretherapy and posttherapy parameters, including a posttherapy decline in PSA of 50% and 80% from baseline. RESULTS In the univariate analysis, initial Karnofsky performance status (KPS) > or = 80% was associated with a favorable outcome (P = .005), while age, extent of disease on bone scan, and individual sites of metastatic disease were not significant. No difference in survival was observed between patients with measurable or assessable (bone only) disease. Initial hemoglobin (HGB; P = .0012), alkaline phosphatase (ALK; P = .0015), and lactate dehydrogenase (LDH; P = .0002) levels were significant discriminators, while the initial PSA was not. Using a landmark analysis, a significantly longer median survival rate was observed for patients with a > or = 50% decline in PSA (median not reached) versus patients with a less than 50% decline in PSA (median, 8.6 months; P = .0001). Multivariate analysis using the Cox proportional hazards model showed that a > or = 50% decline in PSA (P = .0004) and the natural log of LDH (P = .0001) were the two most significant variables predicting survival. The model was confirmed on an independent data set from the Norwegian Radium Hospital (NRH) in Oslo, Norway. CONCLUSION The results suggest that posttherapy PSA declines can be used as a surrogate end point to evaluate new agents in hormone-refractory prostate cancer. The criteria for response need prospective validation in phase III trials.

scholarly journals Randomised phase III study of intravenous vinorelbine plus hormone therapy versus hormone therapy alone in hormone-refractory prostate cancer

2004 ◽  
Vol 15 (11) ◽  
pp. 1613-1621 ◽  
Author(s):  
R.P. Abratt ◽  
D. Brune ◽  
M.-A. Dimopoulos ◽  
J. Kliment ◽  
J. Breza ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Hormone Therapy ◽  
Phase Iii ◽  
Hormone Refractory Prostate Cancer ◽  
Phase Iii Study ◽  
Hormone Refractory
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