title: Activity of second-line chemotherapy in docetaxel-refractory hormone-refractory prostate cancer patients : randomized phase 2 study of ixabepilone or mitoxantrone and prednisone.
abstract: BACKGROUND
  This randomized, noncomparative, multicenter, clinical trial evaluated ixabepilone or mitoxantrone/prednisone (MP) as second-line chemotherapy for taxane-refractory, hormone-refractory, prostate cancer (HRPC).
  
  
  METHODS
  Patients with HRPC that progressed during or within 60 days of cessation of taxane chemotherapy were randomly selected with equal probability to ixabepilone 35 mg/m(2) intravenously every 3 weeks, or mitoxantrone 14 mg/m(2) intravenously every 3 weeks and prednisone 5 mg orally twice daily. Treatment continued until progression or toxicity; crossover was allowed.
  
  
  RESULTS
  Forty-one patients were accrued to each arm of the study. The median number of cycles administered for each arm was 3. Median survival from protocol entry was 10.4 months with ixabepilone and 9.8 months with MP. Prostate-specific antigen (PSA) declines of >or=50% were observed in 17% of ixabepilone (95% CI, 7-32) and 20% of second-line MP patients (95% CI, 9-35). Partial responses were observed in 1 of 24 ixabepilone and in 2 of 21 MP patients with evaluable measurable disease. Median duration of second-line ixabepilone and MP treatment was 2.2 months and 2.3 months, respectively. For third-line crossover treatment, PSA declines of >or=50% were observed in 3 of 27 ixabepilone-treated and 4 of 15 MP-treated patients. Prior taxane response was associated with an increased likelihood of second-line ixabepilone or MP response. Low baseline lactate dehydrogenase and absence of visceral metastases independently predicted improved survival. The most common grade 3/4 toxicity associated with second-line treatment was neutropenia (54% of ixabepilone patients and 63% of MP patients).
  
  
  CONCLUSIONS
  Ixabepilone and MP had modest activity as second-line chemotherapy for docetaxel-refractory HRPC. The median survival for the entire cohort treated in this study was 9.8 months.
authors.affiliation: Department of Medicine, University of California at San Francisco, Comprehensive Cancer Center, San Francisco, California, USA. jrosenbe@medicine.ucsf.edu
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Rosenberg
authors.forename: Vivian K
authors.initials: VK
authors.lastname: Weinberg
authors.forename: W Kevin
authors.initials: WK
authors.lastname: Kelly
authors.forename: Dror
authors.initials: D
authors.lastname: Michaelson
authors.forename: Maha H
authors.initials: MH
authors.lastname: Hussain
authors.forename: George
authors.initials: G
authors.lastname: Wilding
authors.forename: Mitchell
authors.initials: M
authors.lastname: Gross
authors.forename: Douglass
authors.initials: D
authors.lastname: Hutcheon
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Small
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000556:secondary; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018592:Cross-Over Studies; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D034261:Epothilones / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000473:pathology; D011241:Prednisone / Q000008:administration & dosage; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016879:Salvage Therapy; D015996:Survival Rate; D043823:Taxoids / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D034261:Epothilones; D043823:Taxoids; D000077143:Docetaxel; D008942:Mitoxantrone; D017430:Prostate-Specific Antigen; C430592:ixabepilone; D011241:Prednisone