Phase II study of estramustine and vinblastine, two microtubule inhibitors, in hormone-refractory prostate cancer

Gary R. Hudes, Richard E. Greenberg, Robert L. Krigel, S. Fox, Richard M. Scher, Samuel Litwin, Perry Watts, L Speicher, Kenneth D. Tew, Robert L. Comis

Research output: Contribution to journalArticlepeer-review

257 Scopus citations

Abstract

Purpose: 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. Patients and 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 ≥ 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 (≥ 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%. Conclusion: We conclude that EMP and vinblastine is an active combination in hormone-refractory prostate cancer.

Original languageEnglish
Pages (from-to)1754-1761
Number of pages8
JournalJournal of Clinical Oncology
Volume10
Issue number11
DOIs
StatePublished - 1992

Keywords

  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols/pharmacology
  • Drug Resistance
  • Estramustine/administration & dosage
  • Gonadal Steroid Hormones/therapeutic use
  • Humans
  • Male
  • Microtubules/drug effects
  • Middle Aged
  • Pain Measurement
  • Prostate-Specific Antigen/blood
  • Prostatic Neoplasms/blood
  • Survival Analysis
  • Vinblastine/administration & dosage

Fingerprint

Dive into the research topics of 'Phase II study of estramustine and vinblastine, two microtubule inhibitors, in hormone-refractory prostate cancer'. Together they form a unique fingerprint.

Cite this