title: A phase II trial of dexamethasone, vitamin D, and carboplatin in patients with hormone-refractory prostate cancer.
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.
authors.affiliation: Department of Medicine, University of Colorado Health Sciences Center, Aurora, CO 80045-0511, USA. thomas.flaig@uchsc.edu
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Flaig
authors.forename: Albaha
authors.initials: A
authors.lastname: Barqawi
authors.forename: Gary
authors.initials: G
authors.lastname: Miller
authors.forename: Madeleine
authors.initials: M
authors.lastname: Kane
authors.forename: Chan
authors.initials: C
authors.lastname: Zeng
authors.forename: E David
authors.initials: ED
authors.lastname: Crawford
authors.forename: L Michael
authors.initials: LM
authors.lastname: Glodé
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome; D014807:Vitamin D / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*
chemical_list: D000726:Androgen Antagonists; D014807:Vitamin D; D003907:Dexamethasone; D016190:Carboplatin; D017430:Prostate-Specific Antigen