title: Phase II study of estramustine and vinblastine, two microtubule inhibitors, in hormone-refractory prostate cancer.
abstract: OBJECTIVE
  Estramustine phosphate (EMP) and vinblastine are two microtubule inhibitors with distinct molecular targets and at least additive antimicrotubule effects in vitro. Their modest single-agent activities in hormone-refractory prostate cancer, nonoverlapping toxicities, and lack of cross-resistance prompted a phase II trial in hormone-refractory prostate cancer.
  
  
  METHODS
  Thirty-six assessable patients at the Fox Chase Cancer Center and seven Fox Chase Cancer Center Network institutions were treated with oral EMP 600 mg/m2 on days 1 to 42 and vinblastine 4 mg/m2 intravenously (IV) once a week for 6 weeks. Courses were repeated every 8 weeks. Response assessment was based on a change in serum prostate-specific antigen (PSA) levels and was correlated with change in pain scores.
  
  
  RESULTS
  PSA decreased from baseline by at least 50% in 22 patients (61.1%) and by > or = 75% in eight patients (22.2%). A 50% or more decrease in PSA on three successive 2-week measurements together with an improved or stable pain score, performance status, and measurable soft tissue disease (if present) was required for a partial response (PR), which occurred in 11 patients for an overall response rate of 30.5% (95% confidence interval, 15.6% to 45.6%). In seven patients with measurable nonosseous disease, there was one PR (14%) and one minor response (MR). In 28 patients with assessable pain, major pain responses occurred in 12 (42.9%). PSA response (> or = 50% decrease times three measurements) was predictive of major pain response with a 93.7% specificity, a 50% sensitivity, and a positive predictive value of 85.7%.
  
  
  CONCLUSIONS
  We conclude that EMP and vinblastine is an active combination in hormone-refractory prostate cancer.
authors.affiliation: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111.
authors.forename: G R
authors.initials: GR
authors.lastname: Hudes
authors.forename: R
authors.initials: R
authors.lastname: Greenberg
authors.forename: R L
authors.initials: RL
authors.lastname: Krigel
authors.forename: S
authors.initials: S
authors.lastname: Fox
authors.forename: R
authors.initials: R
authors.lastname: Scher
authors.forename: S
authors.initials: S
authors.lastname: Litwin
authors.forename: P
authors.initials: P
authors.lastname: Watts
authors.forename: L
authors.initials: L
authors.lastname: Speicher
authors.forename: K
authors.initials: K
authors.lastname: Tew
authors.forename: R
authors.initials: R
authors.lastname: Comis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D004351:Drug Resistance; D004961:Estramustine / Q000008:administration & dosage; D012739:Gonadal Steroid Hormones / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008870:Microtubules / Q000187:drug effects*; D008875:Middle Aged; D010147:Pain Measurement; D017430:Prostate-Specific Antigen / Q000097:blood / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy*; D016019:Survival Analysis; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D012739:Gonadal Steroid Hormones; D004961:Estramustine; D014747:Vinblastine; D017430:Prostate-Specific Antigen