A phase II trial of dexamethasone, vitamin D, and carboplatin in patients with hormone‐refractory prostate cancer

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Abstract
BACKGROUND. A Phase II prospective trial was performed to study the efficacy of combination therapy with dexamethasone, calcitriol (1,25‐dihydroxyvitamin D3), and carboplatin in patients with hormone‐refractory prostate cancer (HRPC). Preclinical data from prostate cancer cell lines suggested a synergistic effect of these therapies. METHODS. All patients had pathologically confirmed prostate cancer with at least 2 consecutive increases in prostate‐specific antigen (PSA). Treatment started with 1 mg of oral dexamethasone given daily with 0.5 mcg of daily calcitriol added at the start of Week 5. Carboplatin (area under the concentration time curve = 2) was started at the beginning of Week 7. Initially, carboplatin was given weekly; however, the protocol was changed later to give carboplatin for the first 4 weeks of a 6‐week cycle. Of 40 patients who consented to participate, 6 patients were ineligible or declined to start therapy, leaving 34 treated patients. The median follow‐up was 80.7 weeks (range, 11.5–260 weeks). RESULTS. A formal PSA response was seen in 13 of 34 treated patients (38.2%; 95% confidence interval [95% CI], 22.2–56.4%). The median overall survival was 97.7 weeks (95% CI, 61–114 weeks). Significant adverse events that were observed during the trial period included 2 deaths (myocardial infarction and cardiogenic shock), 4 patients with Grade 3 neutropenia (according to the National Cancer Institute Common Toxicity Criteria, version 2.0), 2 patients with thrombosis, 2 patients with inflammatory bowel symptoms, and 2 patients with new‐onset diabetes mellitus. CONCLUSIONS. The novel combination of dexamethasone, calcitriol, and carboplatin for patients with HRPC produced a PSA response in 13 of 34 patients and had an acceptable side‐effect profile. Cancer 2006. © 2006 American Cancer Society.