A phase 2 study of carboplatin plus docetaxel in men with metastatic hormone-refractory prostate cancer who are refractory to docetaxel

Robert W. Ross, Tomasz (Tom) Beer, Susanna Jacobus, Glenn J. Bubley, Mary Ellen Taplin, Christopher Ryan, Jiaoti Huang, William K. Oh

    Research output: Contribution to journalArticle

    91 Citations (Scopus)

    Abstract

    BACKGROUND. Prostate cancer is the second leading cause of cancer mortality among men in the U.S. To the authors' knowledge, there is no proven, effective, second-line therapy for docetaxel-refractory disease. Recent data suggest that platinum salts may be effective when combined with taxanes in metastatic hormone-refractory prostate cancer (HRPC). The authors conducted a phase 2 trial of docetaxel plus carboplatin chemotherapy in this disease setting. METHODS. Eligible men had metastatic HRPC that had progressed during or within 45 days after the completion of docetaxel-based chemotherapy. Patients were treated with intravenous docetaxel at a dose of 60 mg/m2 plus carboplatin at an area under the curve of 4 once every 21 days until they had either disease progression or unacceptable toxicity. RESULTS. Thirty-four patients were enrolled. Therapy was tolerated reasonably well; Grade 3 leukopenia (graded according to the Common Toxicity Criteria grading system) was the most common adverse event (experienced by 56% of patients), but there was only 1 episode of febrile neutropenia reported. Prostate-specific antigen (PSA) declines ≥50% were noted in 18% of patients, and measurable responses were observed in 14%. The median duration of PSA response was 5.7 months. The median progression-free survival was 3 months, and the median overall survival was 12.4 months. Patients were more likely to respond to the combination if they previously had responded to docetaxel. CONCLUSIONS. In men with HRPC who developed progressive disease during or shortly after treatment with docetaxel, the addition of carboplatin resulted in modest additional activity. Taxane-refractory HRPC is an area of unmet need, and the current trial has provided evidence that platinum chemotherapy may be an important therapeutic option.

    Original languageEnglish (US)
    Pages (from-to)521-526
    Number of pages6
    JournalCancer
    Volume112
    Issue number3
    DOIs
    StatePublished - Feb 1 2008

    Fingerprint

    docetaxel
    Carboplatin
    Prostatic Neoplasms
    Hormones
    Prostate-Specific Antigen
    Platinum
    Drug Therapy
    Taxoids
    Febrile Neutropenia
    Leukopenia
    Therapeutics
    Disease-Free Survival
    Area Under Curve
    Disease Progression
    Salts

    Keywords

    • Carboplatin
    • Chromogranin A
    • Docetaxel-refractory
    • Prostate cancer

    ASJC Scopus subject areas

    • Cancer Research
    • Oncology

    Cite this

    A phase 2 study of carboplatin plus docetaxel in men with metastatic hormone-refractory prostate cancer who are refractory to docetaxel. / Ross, Robert W.; Beer, Tomasz (Tom); Jacobus, Susanna; Bubley, Glenn J.; Taplin, Mary Ellen; Ryan, Christopher; Huang, Jiaoti; Oh, William K.

    In: Cancer, Vol. 112, No. 3, 01.02.2008, p. 521-526.

    Research output: Contribution to journalArticle

    Ross, Robert W. ; Beer, Tomasz (Tom) ; Jacobus, Susanna ; Bubley, Glenn J. ; Taplin, Mary Ellen ; Ryan, Christopher ; Huang, Jiaoti ; Oh, William K. / A phase 2 study of carboplatin plus docetaxel in men with metastatic hormone-refractory prostate cancer who are refractory to docetaxel. In: Cancer. 2008 ; Vol. 112, No. 3. pp. 521-526.
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    title = "A phase 2 study of carboplatin plus docetaxel in men with metastatic hormone-refractory prostate cancer who are refractory to docetaxel",
    abstract = "BACKGROUND. Prostate cancer is the second leading cause of cancer mortality among men in the U.S. To the authors' knowledge, there is no proven, effective, second-line therapy for docetaxel-refractory disease. Recent data suggest that platinum salts may be effective when combined with taxanes in metastatic hormone-refractory prostate cancer (HRPC). The authors conducted a phase 2 trial of docetaxel plus carboplatin chemotherapy in this disease setting. METHODS. Eligible men had metastatic HRPC that had progressed during or within 45 days after the completion of docetaxel-based chemotherapy. Patients were treated with intravenous docetaxel at a dose of 60 mg/m2 plus carboplatin at an area under the curve of 4 once every 21 days until they had either disease progression or unacceptable toxicity. RESULTS. Thirty-four patients were enrolled. Therapy was tolerated reasonably well; Grade 3 leukopenia (graded according to the Common Toxicity Criteria grading system) was the most common adverse event (experienced by 56{\%} of patients), but there was only 1 episode of febrile neutropenia reported. Prostate-specific antigen (PSA) declines ≥50{\%} were noted in 18{\%} of patients, and measurable responses were observed in 14{\%}. The median duration of PSA response was 5.7 months. The median progression-free survival was 3 months, and the median overall survival was 12.4 months. Patients were more likely to respond to the combination if they previously had responded to docetaxel. CONCLUSIONS. In men with HRPC who developed progressive disease during or shortly after treatment with docetaxel, the addition of carboplatin resulted in modest additional activity. Taxane-refractory HRPC is an area of unmet need, and the current trial has provided evidence that platinum chemotherapy may be an important therapeutic option.",
    keywords = "Carboplatin, Chromogranin A, Docetaxel-refractory, Prostate cancer",
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    T1 - A phase 2 study of carboplatin plus docetaxel in men with metastatic hormone-refractory prostate cancer who are refractory to docetaxel

    AU - Ross, Robert W.

    AU - Beer, Tomasz (Tom)

    AU - Jacobus, Susanna

    AU - Bubley, Glenn J.

    AU - Taplin, Mary Ellen

    AU - Ryan, Christopher

    AU - Huang, Jiaoti

    AU - Oh, William K.

    PY - 2008/2/1

    Y1 - 2008/2/1

    N2 - BACKGROUND. Prostate cancer is the second leading cause of cancer mortality among men in the U.S. To the authors' knowledge, there is no proven, effective, second-line therapy for docetaxel-refractory disease. Recent data suggest that platinum salts may be effective when combined with taxanes in metastatic hormone-refractory prostate cancer (HRPC). The authors conducted a phase 2 trial of docetaxel plus carboplatin chemotherapy in this disease setting. METHODS. Eligible men had metastatic HRPC that had progressed during or within 45 days after the completion of docetaxel-based chemotherapy. Patients were treated with intravenous docetaxel at a dose of 60 mg/m2 plus carboplatin at an area under the curve of 4 once every 21 days until they had either disease progression or unacceptable toxicity. RESULTS. Thirty-four patients were enrolled. Therapy was tolerated reasonably well; Grade 3 leukopenia (graded according to the Common Toxicity Criteria grading system) was the most common adverse event (experienced by 56% of patients), but there was only 1 episode of febrile neutropenia reported. Prostate-specific antigen (PSA) declines ≥50% were noted in 18% of patients, and measurable responses were observed in 14%. The median duration of PSA response was 5.7 months. The median progression-free survival was 3 months, and the median overall survival was 12.4 months. Patients were more likely to respond to the combination if they previously had responded to docetaxel. CONCLUSIONS. In men with HRPC who developed progressive disease during or shortly after treatment with docetaxel, the addition of carboplatin resulted in modest additional activity. Taxane-refractory HRPC is an area of unmet need, and the current trial has provided evidence that platinum chemotherapy may be an important therapeutic option.

    AB - BACKGROUND. Prostate cancer is the second leading cause of cancer mortality among men in the U.S. To the authors' knowledge, there is no proven, effective, second-line therapy for docetaxel-refractory disease. Recent data suggest that platinum salts may be effective when combined with taxanes in metastatic hormone-refractory prostate cancer (HRPC). The authors conducted a phase 2 trial of docetaxel plus carboplatin chemotherapy in this disease setting. METHODS. Eligible men had metastatic HRPC that had progressed during or within 45 days after the completion of docetaxel-based chemotherapy. Patients were treated with intravenous docetaxel at a dose of 60 mg/m2 plus carboplatin at an area under the curve of 4 once every 21 days until they had either disease progression or unacceptable toxicity. RESULTS. Thirty-four patients were enrolled. Therapy was tolerated reasonably well; Grade 3 leukopenia (graded according to the Common Toxicity Criteria grading system) was the most common adverse event (experienced by 56% of patients), but there was only 1 episode of febrile neutropenia reported. Prostate-specific antigen (PSA) declines ≥50% were noted in 18% of patients, and measurable responses were observed in 14%. The median duration of PSA response was 5.7 months. The median progression-free survival was 3 months, and the median overall survival was 12.4 months. Patients were more likely to respond to the combination if they previously had responded to docetaxel. CONCLUSIONS. In men with HRPC who developed progressive disease during or shortly after treatment with docetaxel, the addition of carboplatin resulted in modest additional activity. Taxane-refractory HRPC is an area of unmet need, and the current trial has provided evidence that platinum chemotherapy may be an important therapeutic option.

    KW - Carboplatin

    KW - Chromogranin A

    KW - Docetaxel-refractory

    KW - Prostate cancer

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