Phase 2 Study of Weekly Paclitaxel Plus Estramustine in Metastatic Hormone-Refractory Prostate Carcinoma: ECOG-ACRIN Cancer Research Group (E1898) Trial

Yu Ning Wong*, Judith Manola, Gary R. Hudes, Bruce J. Roth, Judd W. Moul, Andrea M. Barsevick, Richard M. Scher, Michael J. Volk, David J. Vaughn, Stephen D. Williams, Michael J. Fisch, David Cella, Michael A. Carducci, George Wilding

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

To assess the combination of estramustine and weekly paclitaxel with metastatic castration-resistant prostate cancer, 74 eligible patients were treated. The response rate was not better than those noted in subsequent phase 3 studies of docetaxel-based therapies. Because better-tolerated therapies have since been approved, we cannot recommend further development of this regimen. Introduction: This multicenter phase 2 study assessed the combination of estramustine and weekly paclitaxel with metastatic castration-resistant prostate cancer (CRPC). Patients and Methods: We enrolled 77 patients who had received no prior chemotherapy for CRPC between 1998 and 2000; a total of 74 subjects were eligible for the study. Each 8-week cycle included paclitaxel 90 mg/m2 provided intravenously weekly for 6 weeks, followed by 2 weeks off therapy and oral estramustine 280 mg twice daily for 3 days beginning 24 hours before the first dose of paclitaxel. The primary end point was rate of objective or prostate-specific antigen (PSA) response at 16 weeks. A 50% response rate was considered of further interest. Results: Eligible patients received a median of 3 cycles (range, 1-10 cycles). The response rate among patients with measurable disease was 34% (95% confidence interval [CI], 19-52). The PSA response rate was 58% (95% CI, 47-70). Clinical benefit rate was 45% (95% CI, 33-57). The median progression-free survival was 5.9 months (95% CI, 4.4-6.7). The median overall survival was 17.6 months (95% CI, 14.6-20.8). The most common clinical grade 3/4 toxicities were fatigue (14%) and sensory neuropathy (7%). Grade 3/4 hematologic toxicities included lymphopenia (21%) and anemia (9%). There was one toxicity-related death. Quality-of-life scores improved by week 8, but the change was not statistically significant. Conclusion: The combination has activity defined by PSA declines in CRPC but did not meet the protocol-specified end point for efficacy as defined by objective response rate. Since this study was conducted, more effective, better-tolerated regimens have been developed.

Original languageEnglish (US)
Pages (from-to)e315-e322
JournalClinical Genitourinary Cancer
Volume16
Issue number2
DOIs
StatePublished - Apr 2018

Keywords

  • Castration resistant
  • Chemotherapy
  • Clinical trials
  • Metastases
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Urology

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