title: Phase III trial of androgen ablation with or without three cycles of systemic chemotherapy for advanced prostate cancer.
abstract: OBJECTIVE
  We conducted a phase III trial in patients with previously untreated metastatic prostate cancer to test the hypothesis that three 8-week cycles of ketoconazole and doxorubicin alternating with vinblastine and estramustine, given in addition to standard androgen deprivation, would delay the appearance of castrate-resistant disease.
  
  
  METHODS
  Eligible patients had metastatic prostate cancer threatening enough to justify sustained androgen ablation and were fit enough for chemotherapy. The primary end point was time to castrate-resistant progression as shown by increasing prostate-specific antigen, new radiographic lesions, worsening cancer-related symptoms, or receipt of any other systemic therapy.
  
  
  RESULTS
  Three hundred six patients were registered; 286 are reported. Median time to progression was 24 months (95% CI, 18 to 39 months) in the standard therapy arm, and 35 months (95% CI, 26 to 44 months) in the chemohormonal group (P = .39). At median follow-up of 6.4 years, overall survival was 5.4 years (95% CI, 4.7 to 7.8 years) in the standard therapy arm versus 6.1 years (95% CI, 5.1 to 10.1 years; P = .41). Prostate-specific antigen kinetics at the time of androgen ablation and the nadir after hormone treatment were strongly correlated with survival. Chemotherapy significantly increased the burden of therapy, with 51% of patients experiencing an adverse event of grade 3 or worse, especially thromboembolic events.
  
  
  CONCLUSIONS
  There is no role for ketoconazole and doxorubicin alternating with vinblastine and estramustine before emergence of a castrate-resistant phenotype.
authors.affiliation: Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, 1155 Pressler, CPB7.3462, Houston, TX 77030, USA. rmillika@mdanderson.org
authors.forename: Randall E
authors.initials: RE
authors.lastname: Millikan
authors.forename: Sijin
authors.initials: S
authors.lastname: Wen
authors.forename: Lance C
authors.initials: LC
authors.lastname: Pagliaro
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Brown
authors.forename: Brenda
authors.initials: B
authors.lastname: Moomey
authors.forename: Kim-Anh
authors.initials: KA
authors.lastname: Do
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Logothetis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004317:Doxorubicin / Q000008:administration & dosage; D004961:Estramustine / Q000008:administration & dosage; D006801:Humans; D007654:Ketoconazole / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D000726:Androgen Antagonists; D000903:Antibiotics, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D004961:Estramustine; D014747:Vinblastine; D004317:Doxorubicin; D007654:Ketoconazole