Ixabepilone, mitoxantrone, and prednisone for metastatic castration-resistant prostate cancer after docetaxel-based therapy: A phase 2 study of the department of defense prostate cancer clinical trials consortium

Andrea L. Harzstark, Jonathan E. Rosenberg, Vivian K. Weinberg, Jeremy Sharib, Charles J. Ryan, David C. Smith, Lance C. Pagliaro, Tomasz M. Beer, Glenn Liu, Eric J. Small

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

BACKGROUND: Mitoxantrone plus prednisone and ixabepilone each have modest activity as monotherapy for second-line chemotherapy in patients with docetaxel-refractory castration-resistant prostate cancer. Clinical noncross-resistance was previously observed. Phase 1 testing determined the maximum tolerated dose and dose-limiting toxicities with the combination regimen; a phase 2 study was conducted to evaluate the activity of the combination. METHODS: Patients with metastatic progressive castration-resistant prostate cancer during or after 3 or more cycles of taxane-based chemotherapy enrolled in a phase 2 multicenter study of ixabepilone 35 mg/m2 and mitoxantrone 12 mg/m2 administered on Day 1 every 21 days with pegfilgrastim support, along with prednisone 5 mg twice daily. Patients were evaluated for disease response and toxicity. RESULTS: Results are reported for the 56 evaluable patients. Twenty-five (45%; 95% confidence interval [CI], 31%-59%) experienced confirmed ≥50% prostate-specific antigen (PSA) declines, 33 (59%; 95% CI, 45%-72%) experienced confirmed ≥30% PSA declines, and 8 of 36 patients (22%; 95% CI, 10%-39%) with measurable disease experienced objective responses. Median time to PSA or objective progression was 4.4 months (95% CI, 3.5-5.6), and median progression-free survival was also 4.4 months (95% CI, 3.0-6.0). Median overall survival was 12.5 months (95% CI, 10.2-15.9). Thirty-two percent of patients experienced grade 3 of 4 neutropenia, and 11% experienced grade 3 or higher neutropenic infections, including 1 treatment-related death. Grade 2 and 3 neuropathy occurred in 11% and 12.5% of patients, respectively. CONCLUSIONS: These results suggest that the combination of ixabepilone and mitoxantrone is both feasible and active in castration-resistant prostate cancer and requires dosing with pegfilgrastim.

Original languageEnglish (US)
Pages (from-to)2419-2425
Number of pages7
JournalCancer
Volume117
Issue number11
DOIs
StatePublished - Jun 1 2011

Keywords

  • Chemotherapy
  • Docetaxel
  • Ixabepilone
  • Metastatic
  • Mitoxantrone
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Ixabepilone, mitoxantrone, and prednisone for metastatic castration-resistant prostate cancer after docetaxel-based therapy: A phase 2 study of the department of defense prostate cancer clinical trials consortium'. Together they form a unique fingerprint.

  • Cite this

    Harzstark, A. L., Rosenberg, J. E., Weinberg, V. K., Sharib, J., Ryan, C. J., Smith, D. C., Pagliaro, L. C., Beer, T. M., Liu, G., & Small, E. J. (2011). Ixabepilone, mitoxantrone, and prednisone for metastatic castration-resistant prostate cancer after docetaxel-based therapy: A phase 2 study of the department of defense prostate cancer clinical trials consortium. Cancer, 117(11), 2419-2425. https://doi.org/10.1002/cncr.25810