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Keywords:

  • prostate neoplasms;
  • carboplatin;
  • dexamethasone;
  • vitamin D;
  • metronomic;
  • prostate-specific antigen;
  • human;
  • male;
  • antineoplastic combined chemotherapy protocols

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.