Peptide vaccines with low-dose dexamethasone versus dexamethasone alone for chemotherapy-naive castration resistant prostate cancer: A randomized phase II study.
3 Background: We previously developed MHC class I restricted peptide vaccines for prostate cancer and carried out a phase 1 trial for castration resistant prostate cancer (CRPC) patients to assess safety and immunological evaluation. In the present study, we conducted a randomized phase 2 trial to evaluate the efficacy of peptide vaccination therapy for chemotherapy-naive CRPC patients. Methods: Early-stage CRPC (PSA<10ng/ml) patients positive for HLA-A02 or A24 or A3 super family were randomized into two treatment groups; peptide vaccine with low dose (1mg/day) dexamethasone (Dx) versus low dose Dx alone. Patients were vaccinated subcutaneously with 3 mg of selected peptides (max. 4 kinds) 6 times at two weeks interval. Dx 1mg/day p.o. was started on the first day of peptide vaccination. Toxicity was assessed monthly, and immunological responses such as cytotoxic T lymphocyte activity and clinical responses were evaluated every 3 months. The primary endpoint of this study is progression-free survival including serum PSA. Secondary endpoints are overall survival and safety. Results: A total of 83 chemotherapy-naive CRPC patients were selected for this trial. Of these 10 patients were excluded due to HLA type mismatch and exclusion criteria. 73 patients were enrolled and randomized; 37 in the vaccine treatment group and 36 in the Dx group. One patient in the Dx group self-withdrew from the study immediate after the randomization. Median time to PSA failure in the vaccine group was significant longer than the Dx group; 602 days vs 210 days, p<0.001 (Table). Conclusions: These findings suggest that combination therapy of peptide vaccines and low dose dexamethasone may be a promising tool for chemotherapy-naive CRPC patients. Clinical trial information: UMIN000000959.[Table: see text]