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 Citations (Scopus)

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
Externally publishedYes

Fingerprint

docetaxel
Mitoxantrone
Castration
Prednisone
Prostatic Neoplasms
Clinical Trials
Confidence Intervals
Prostate-Specific Antigen
Therapeutics
Drug Therapy
Maximum Tolerated Dose
ixabepilone
Neutropenia
Multicenter Studies
Disease-Free Survival

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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

In: Cancer, Vol. 117, No. 11, 01.06.2011, p. 2419-2425.

Research output: Contribution to journalArticle

Harzstark, Andrea L. ; Rosenberg, Jonathan E. ; Weinberg, Vivian K. ; Sharib, Jeremy ; Ryan, Charles J. ; Smith, David C. ; Pagliaro, Lance C. ; Beer, Tomasz M. ; Liu, Glenn ; Small, Eric J. / 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. In: Cancer. 2011 ; Vol. 117, No. 11. pp. 2419-2425.
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title = "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",
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.",
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author = "Harzstark, {Andrea L.} and Rosenberg, {Jonathan E.} and Weinberg, {Vivian K.} and Jeremy Sharib and Ryan, {Charles J.} and Smith, {David C.} and Pagliaro, {Lance C.} and Beer, {Tomasz M.} and Glenn Liu and Small, {Eric J.}",
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T2 - A phase 2 study of the department of defense prostate cancer clinical trials consortium

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AU - Rosenberg, Jonathan E.

AU - Weinberg, Vivian K.

AU - Sharib, Jeremy

AU - Ryan, Charles J.

AU - Smith, David C.

AU - Pagliaro, Lance C.

AU - Beer, Tomasz M.

AU - Liu, Glenn

AU - Small, Eric J.

PY - 2011/6/1

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N2 - 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.

AB - 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.

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