A phase 2 study of carboplatin plus docetaxel in men with metastatic hormone-refractory prostate cancer who are refractory to docetaxel.
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.
Ross
Robert W
RW
Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Beer
Tomasz M
TM
Jacobus
Susanna
S
Bubley
Glenn J
GJ
Taplin
Mary-Ellen
ME
Ryan
Christopher W
CW
Huang
Jiaoti
J
Oh
William K
WK
D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy*; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D016190:Carboplatin / Q000009:adverse effects / Q000627:therapeutic use*; D053379:Chromogranin A / Q000097:blood; D018450:Disease Progression; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D004359:Drug Therapy, Combination; D006801:Humans; D008297:Male; D008875:Middle Aged; D010751:Phosphopyruvate Hydratase / Q000097:blood; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy*; D016019:Survival Analysis; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D053379:Chromogranin A; D043823:Taxoids; D000077143:Docetaxel; D016190:Carboplatin; D017430:Prostate-Specific Antigen; D010751:Phosphopyruvate Hydratase