title: Phase 2 trial of weekly intravenous 1,25 dihydroxy cholecalciferol (calcitriol) in combination with dexamethasone for castration-resistant prostate cancer.
abstract: BACKGROUND
  Preclinical data indicate that there is substantial antitumor activity and synergy between calcitriol and dexamethasone. On the basis of these data, the authors conducted a phase 2 trial of intravenous (iv) calcitriol at a dose of 74 microg weekly (based on a recent phase 1 trial) and dexamethasone in patients with castration-resistant prostate cancer (CRPC).
  
  
  METHODS
  A 2-stage Kepner-Chang design was used. Oral dexamethasone at a dose of 4 mg was given weekly on Days 1 and 2, and iv calcitriol (74 microg over 1 hour) was administered weekly on Day 2 from 4 to 8 hours after the dexamethasone dose in patients with CRPC. Laboratory data were monitored weekly, and renal sonograms, computed tomography scans, and bone scans were obtained every 3 months. Disease response was assessed by using the Response Evaluation Criteria in Solid Tumors (RECIST) and standard criteria for prostate-specific antigen (PSA) response. The calcitriol dose was delineated by from the authors' recent phase 1 trial.
  
  
  RESULTS
  Of 18 evaluable patients, 15 patients were Caucasian (83%). No patients had a complete or partial response by either RECIST or PSA response criteria. Fourteen patients had progressive disease, 2 patients refused to continue treatment (after 64 days and 266 days), and 2 patients remain on the trial (for 306 days and 412 days).The median time to disease progression was 106 days (95% confidence interval, 80-182 days). Fourteen episodes of grade 3 or 4 toxicity were noted in 7 patients (hyperglycemia, hypocalemia, chest pain, dyspnea, hypercalcemia, hypophosphatemia, cardiac arrhythmia, and pain). Only 1 episode of grade 3/ 4 toxicity was related definitely to calcitriol (hypercalcemia). No treatment-related deaths were noted.
  
  
  CONCLUSIONS
  High-dose, iv calcitriol at a dose of 74 microg weekly in combination with dexamethasone was well tolerated but failed to produce a clinical or PSA response in men with CRPC.
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
authors.forename: Manpreet K
authors.initials: MK
authors.lastname: Chadha
authors.forename: Lili
authors.initials: L
authors.lastname: Tian
authors.forename: Terry
authors.initials: T
authors.lastname: Mashtare
authors.forename: Valencia
authors.initials: V
authors.lastname: Payne
authors.forename: Carrie
authors.initials: C
authors.lastname: Silliman
authors.forename: Ellis
authors.initials: E
authors.lastname: Levine
authors.forename: Michael
authors.initials: M
authors.lastname: Wong
authors.forename: Candace
authors.initials: C
authors.lastname: Johnson
authors.forename: Donald L
authors.initials: DL
authors.lastname: Trump
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002117:Calcitriol / Q000008:administration & dosage*; D002118:Calcium / Q000097:blood; D003404:Creatinine / Q000097:blood; D003907:Dexamethasone / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D019233:Retreatment
chemical_list: D003907:Dexamethasone; D003404:Creatinine; D017430:Prostate-Specific Antigen; D002117:Calcitriol; D002118:Calcium