EVALUATION OF PHASE I II CLINICAL-TRIALS IN PROSTATE-CANCER WITH DENDRITIC CELLS AND PSMA PEPTIDES/

BACKGROUND. A phase I trial involving patients with advanced prostate cancer was con ducted to assess the safe administration of dendritic c ells (DC) and HLA-A0201-specific prostate-specific membrane antigen (P SMA) peptides (PSM-P1 or -P2). Thirty-three of the phase I participant s were subsequently enrolled in a phase II trial, which involved six i nfusions of DC pulsed with PSM-P1 and -P2 peptides. METHODS. Clinical monitoring was conducted up to 770 days from the start of the phase I study. Data collected included: complete blood count, bone and total a lkaline phosphatase, prostate markers, physical examination, performan ce status, bone scan, ProstaScint(R) scan, and chest X-ray, as well as assays to monitor cellular immune responses. RESULTS. Nine partial re sponders were identified in the phase II study based on National Prost ate Cancer Project (NPCP) criteria, plus 50% reduction of prostate-spe cific antigen. Four of the partial responders were also responders in the phase I study, with an average response duration of 225 days. Thei r combined average total response period was over 370 days. Five other responders were nonresponders in the phase I study. Their average par tial response period was 196 days. CONCLUSIONS. The responses observed in the phase I and Il clinical trials were significant and of long du ration. The partial-responder group included patients who continued to respond from phase I, as well as those who started to respond during the phase IT trial. Prostate 36:39-44, 1998. (C) 1998 Wiley-Liss, Inc.