Phase II study of personalized peptide vaccination for castration-resistant prostate cancer patients who failed in docetaxel-based chemotherapy

BACKGROUND Docetaxel-based chemotherapy (DBC) showed limited clinical efficacy for castration-resistant prostate cancer (CRPC) patients. To explore cancer vaccine as a new treatment modality, we conducted a phase II study of personalized peptide vaccine (PPV) for DBC-resistant CRPC patients. METHODS Twenty DBC-resistant CRPC patients and 22 patients with no prior DBC, as a control, were treated with PPV using peptides chosen from 31 peptides in patients, respectively. Cytokines, inflammatory markers, and immune responses were measured as candidate biomarkers. DBC-resistant CRPC patients without PPV was set as a historical control for evaluation of clinical benefit of PPV. RESULTS Median overall survival (OS) time from the first vaccination was 14.8 months or not reached in DBC-resistant CRPC patients and patients with no prior DBC (log-rank; P = 0.07), respectively. Median OS time from the first day of progression disease was 17.8 and 10.5 months in DBC-resistant CRPC patients receiving PPV and those with no PPV (P = 0.1656), respectively. Elevated IL-6 levels before vaccination was an unfavorable factor for OS of DBC-resistant CRPC patients (P = 0.0161, hazard ratio (HR): 0.024, 95% CI:0.001–0.499) as well as all 42 patients with PPV(P = 0.0011, HR: 0.212, 95% CI:0.068–0.661) by multivariable analysis. CONCLUSIONS Further clinical study of PPV is recommended for DBC-resistant CRPC patients, because of the safety and possible prolongation of MST. Control of elevated IL-6 by combined therapy may provide much better clinical outcome. Prostate 72:834–845, 2012. © 2011 Wiley Periodicals, Inc.