title: Double-blinded randomized study of high-dose calcitriol plus docetaxel compared with placebo plus docetaxel in androgen-independent prostate cancer: a report from the ASCENT Investigators.
abstract: OBJECTIVE
  To compare the safety and activity of DN-101, a new high-dose oral formulation of calcitriol designed for cancer therapy, and docetaxel with placebo and docetaxel.
  
  
  METHODS
  Patients with progressive metastatic androgen-independent prostate cancer and adequate organ function received weekly docetaxel 36 mg/m2 intravenously for 3 weeks of a 4-week cycle combined with either 45 microg DN-101 or placebo taken orally 1 day before docetaxel. The primary end point was prostate-specific antigen (PSA) response within 6 months of enrollment, defined as a 50% reduction confirmed at least 4 weeks later.
  
  
  RESULTS
  Two hundred fifty patients were randomly assigned. Baseline characteristics were similar in both arms. Within 6 months, PSA responses were seen in 58% in DN-101 patients and 49% in placebo patients (P = .16). Overall, PSA response rates were 63% (DN-101) and 52% (placebo), P = .07. Patients in the DN-101 group had a hazard ratio for death of 0.67 (P = .04) in a multivariate analysis that included baseline hemoglobin and performance status. Median survival has not been reached for the DN-101 arm and is estimated to be 24.5 months using the hazard ratio, compared with 16.4 months for placebo. Grade 3/4 adverse events occurred in 58% of DN-101 patients and in 70% of placebo-treated patients (P = .07). Most common grade 3/4 toxicities for DN-101 versus placebo were neutropenia (10% v 8%), fatigue (8% v 16%), infection (8% v 13%), and hyperglycemia (6% v 12%).
  
  
  CONCLUSIONS
  This study suggests that DN-101 treatment was associated with improved survival, but this will require confirmation because survival was not a primary end point. The addition of weekly DN-101 did not increase the toxicity of weekly docetaxel.
authors.affiliation: Division of Hematology and Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA. beert@ohsu.edu
authors.forename: Tomasz M
authors.initials: TM
authors.lastname: Beer
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Ryan
authors.forename: Peter M
authors.initials: PM
authors.lastname: Venner
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Petrylak
authors.forename: Gurkamal S
authors.initials: GS
authors.lastname: Chatta
authors.forename: J Dean
authors.initials: JD
authors.lastname: Ruether
authors.forename: Charles H
authors.initials: CH
authors.lastname: Redfern
authors.forename: Louis
authors.initials: L
authors.lastname: Fehrenbacher
authors.forename: Mansoor N
authors.initials: MN
authors.lastname: Saleh
authors.forename: David M
authors.initials: DM
authors.lastname: Waterhouse
authors.forename: Michael A
authors.initials: MA
authors.lastname: Carducci
authors.forename: Daniel
authors.initials: D
authors.lastname: Vicario
authors.forename: Robert
authors.initials: R
authors.lastname: Dreicer
authors.forename: Celestia S
authors.initials: CS
authors.lastname: Higano
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Ahmann
authors.forename: Kim N
authors.initials: KN
authors.lastname: Chi
authors.forename: W David
authors.initials: WD
authors.lastname: Henner
authors.forename: Alan
authors.initials: A
authors.lastname: Arroyo
authors.forename: Fong W
authors.initials: FW
authors.lastname: Clow
mesh_terms: D000367:Age Factors; D000368:Aged; D000728:Androgens / Q000378:metabolism*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001707:Biopsy, Needle; D002117:Calcitriol / Q000008:administration & dosage* / Q000009:adverse effects; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010919:Placebos / Q000008:administration & dosage; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D018570:Risk Assessment; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000728:Androgens; D010919:Placebos; D043823:Taxoids; D000077143:Docetaxel; D017430:Prostate-Specific Antigen; D002117:Calcitriol