title: Phase II study on the addition of ASA404 (vadimezan; 5,6-dimethylxanthenone-4-acetic acid) to docetaxel in CRMPC.
abstract: OBJECTIVE
  This randomized phase II study evaluated ASA404 (vadimezan; 5,6-dimethylxanthenone-4-acetic acid) in combination with docetaxel in castration-refractory metastatic prostate cancer (CRMPC).
  
  
  METHODS
  Seventy-four patients with histopathologically confirmed CRMPC previously untreated with chemotherapy were randomized to receive either<or=10 cycles of docetaxel 75 mg/m2 alone (D; n=39) or docetaxel plus ASA404 1,200 mg/m2 (A-D; n=35). Study endpoints included prostate-specific antigen response, tumor response, median time to tumor progression, median survival, and toxicity.
  
  
  RESULTS
  The overall pattern of adverse events was similar in the two groups; however, there was a higher incidence of cardiac adverse events and neutropenia in the A-D group. Coadministration of ASA404 with docetaxel did not affect total systemic exposure of either drug. A higher prostate-specific antigen response rate was reported with A-D versus D (59.4% versus 36.8%), together with a larger median percentage reduction in prostate-specific antigen (84.0% versus 61.9%) and a shorter median time to prostate-specific antigen nadir (105 versus 119 d). Tumor response rate was 23.1% with A-D and 9.1% with D. Time to tumor progression and median survival were similar in the groups (time to tumor progression, 8.7 mo for A-D and 8.4 mo for D; survival, 17.0 mo for A-D and 17.2 mo for D). Hazard ratios for time to tumor progression and survival were 0.81 and 0.80, respectively, favoring A-D; 2-year survival was 33.3% with A-D and 22.8% with D.
  
  
  CONCLUSIONS
  The study met some endpoints (prostate-specific antigen response, tumor response) but not others (i.e., time to tumor progression). The results indicate that the combination of ASA404 with docetaxel has acceptable toxicity, lacks adverse pharmacokinetic interaction, and, overall, has activity in CRMPC.
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA. roberto.pili@roswellpark.org
authors.forename: Roberto
authors.initials: R
authors.lastname: Pili
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rosenthal
authors.forename: Paul N
authors.initials: PN
authors.lastname: Mainwaring
authors.forename: Guy
authors.initials: G
authors.lastname: Van Hazel
authors.forename: Sandy
authors.initials: S
authors.lastname: Srinivas
authors.forename: Robert
authors.initials: R
authors.lastname: Dreicer
authors.forename: Sanjay
authors.initials: S
authors.lastname: Goel
authors.forename: Joseph
authors.initials: J
authors.lastname: Leach
authors.forename: Shirley
authors.initials: S
authors.lastname: Wong
authors.forename: Peter
authors.initials: P
authors.lastname: Clingan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D004562:Electrocardiography / Q000187:drug effects; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D044004:Xanthones / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D043823:Taxoids; D044004:Xanthones; C066668:vadimezan; D000077143:Docetaxel; D017430:Prostate-Specific Antigen