High-dose calcitriol and carboplatin in metastatic androgen-independent prostate cancer.
Calcitriol acts synergistically with carboplatin in preclinical models of adenocarcinoma of the prostate. The authors sought to test high-dose oral calcitriol in combination with carboplatin in patients with metastatic androgen-independent prostate cancer. Seventeen patients received oral calcitriol (0.5 microg/kg) on day 1 and intravenous carboplatin (AUC 7 or AUC 6 in patients with prior radiation) on day 2, repeated every 4 weeks. PSA response was the primary end point and was defined as a 50% reduction confirmed 4 weeks later. Palliative response (2-point reduction or normalization of pain on the present pain intensity [PPI] scale without increased analgesic consumption) was also examined. One of 17 patients (6%, 95% CI, 0-28) achieved a confirmed PSA response. Four patients (24%, 95% CI, 7-49) had PSA reductions ranging from 24 to 38%. Of the 15 patients with a PPI > or = 1 point on entry, 3 (18%, 95% CI, 4-48) met criteria for palliative response. Treatment-related toxicity was mild and generally similar to that expected with single-agent carboplatin. Despite encouraging preclinical evidence, the addition of oral calcitriol to carboplatin in this study was not associated with an increase in the response rate when compared with the reported activity of carboplatin alone.
Beer
Tomasz M
TM
Department of Medicine, Oregon Health & Science University, Portland, Oregon 97239, USA. beert@ohsu.edu
Garzotto
Mark
M
Katovic
Nina M
NM
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002117:Calcitriol / Q000008:administration & dosage / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000627:therapeutic use*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D008297:Male; D008875:Middle Aged; D010166:Palliative Care; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016879:Salvage Therapy
D000970:Antineoplastic Agents; D016190:Carboplatin; D002117:Calcitriol