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/m(2) 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 > or =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.

• Authors: Robert W Ross, Tomasz M Beer, Susanna Jacobus, Glenn J Bubley, Mary-Ellen Taplin, Christopher W Ryan, Jiaoti Huang, William K Oh, Prostate Cancer Clinical Trials Consortium
• Journal: Cancer (Cancer) Vol. 112 Issue 3 Pg. 521-6 (Feb 01 2008) ISSN: 0008-543X [Print] United States
• PMID: 18085595 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antineoplastic Agents
• Biomarkers, Tumor
• Chromogranin A
• Taxoids
• Docetaxel
• Carboplatin
• Prostate-Specific Antigen
• Phosphopyruvate Hydratase

Topics

• Adenocarcinoma (blood, drug therapy)
• Aged
• Aged, 80 and over
• Antineoplastic Agents (adverse effects, therapeutic use)
• Biomarkers, Tumor (blood)
• Carboplatin (adverse effects, therapeutic use)
• Chromogranin A (blood)
• Disease Progression
• Docetaxel
• Drug Resistance, Neoplasm
• Drug Therapy, Combination
• Humans
• Male
• Middle Aged
• Phosphopyruvate Hydratase (blood)
• Prostate-Specific Antigen (blood)
• Prostatic Neoplasms (blood, drug therapy)
• Survival Analysis
• Taxoids (adverse effects, therapeutic use)