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 (Tom) 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

    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 (Tom); 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 (Tom) ; 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.",
    keywords = "Chemotherapy, Docetaxel, Ixabepilone, Metastatic, Mitoxantrone, Prostate cancer",
    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 (Tom)} and Glenn Liu and Small, {Eric J.}",
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    T1 - Ixabepilone, mitoxantrone, and prednisone for metastatic castration-resistant prostate cancer after docetaxel-based therapy

    T2 - A phase 2 study of the department of defense prostate cancer clinical trials consortium

    AU - Harzstark, Andrea L.

    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 (Tom)

    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.

    KW - Chemotherapy

    KW - Docetaxel

    KW - Ixabepilone

    KW - Metastatic

    KW - Mitoxantrone

    KW - Prostate cancer

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