title: Weekly high-dose calcitriol and docetaxel in metastatic androgen-independent prostate cancer.
abstract: OBJECTIVE
  To determine the safety and efficacy of weekly high-dose oral calcitriol (Rocaltrol, Roche Pharmaceuticals, Basel, Switzerland) and docetaxel (Taxotere, Aventis Pharmaceuticals, Bridgewater, NJ) in patients with metastatic androgen-independent prostate cancer (AIPC).
  
  
  METHODS
  Thirty-seven patients were treated with oral calcitriol (0.5 micro g/kg) on day 1 followed by docetaxel (36 mg/m(2)) on day 2, repeated weekly for 6 weeks of an 8-week cycle. Patients maintained a reduced calcium diet and increased oral hydration. Prostate-specific antigen (PSA) response was the primary end point, which was defined as a 50% reduction in PSA level confirmed 4 weeks later.
  
  
  RESULTS
  Thirty of 37 patients (81%; 95% confidence interval [CI], 68% to 94%) achieved a PSA response. Twenty-two patients (59%; 95% CI, 43% to 75%) had a confirmed > 75% reduction in PSA. Eight of the 15 patients with measurable disease (53%; 95% CI, 27% to 79%) had a confirmed partial response. Median time to progression was 11.4 months (95% CI, 8.7 to 14 months), and median survival was 19.5 months (95% CI, 15.3 months to incalculable). Overall survival at 1 year was 89% (95% CI, 74% to 95%). Treatment-related toxicity was generally similar to that expected with single-agent docetaxel. Pharmacokinetics of either calcitriol or docetaxel were not affected by the presence of its companion drug in an exploratory substudy.
  
  
  CONCLUSIONS
  The combination of weekly oral high-dose calcitriol and weekly docetaxel is a well-tolerated regimen for AIPC. PSA and measurable disease response rates as well as time to progression and survival are promising when compared with contemporary phase II studies of single-agent docetaxel in AIPC. Further study of this regimen is warranted.
authors.affiliation: Oregon Health & Science University and Portland VA Medical Center, Portland, OR 97239, USA. beert@ohsu.edu
authors.forename: Tomasz M
authors.initials: TM
authors.lastname: Beer
authors.forename: Kristine M
authors.initials: KM
authors.lastname: Eilers
authors.forename: Mark
authors.initials: M
authors.lastname: Garzotto
authors.forename: Merrill J
authors.initials: MJ
authors.lastname: Egorin
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Lowe
authors.forename: W David
authors.initials: WD
authors.lastname: Henner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D002117:Calcitriol / Q000008:administration & dosage / Q000494:pharmacology; D018572:Disease-Free Survival; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate; D043823:Taxoids
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D017430:Prostate-Specific Antigen; D002117:Calcitriol; D017239:Paclitaxel