Phase II trial of biweekly paclitaxel and cisplatin in advanced breast carcinoma: An Eastern Cooperative Oncology Group Study

Purpose: To determine the efficacy of a biweekly paclitaxel and cisplatin regimen in patients with advanced breast carcinoma, which has previously been reported to produce an 85% response rate in such patients. Patients and Methods: Sixteen patients with metastatic breast carcinoma who had relapsed after prior doxorubicin-containing adjuvant chemotherapy were treated with paclitaxel (90 mg/m²) by intravenous (IV) infusion over 3 hours followed by cisplatin (60 mg/m²) given by IV infusion over 1 hour on an outpatient basis. Treatment was repeated every 2 weeks if the absolute neutrophil count was ≤ 750/μL and platelet count 75,000/μL. After a maximum of eight cycles of paclitaxel/cisplatin, patients received biweekly paclitaxel alone (90 mg/m² with dose escalation). Thirteen patients were assessable for response and all for toxicity. Nine of 13 patients assessable for response (69%) had at least three sites of metastases and 10 patients (77%) had visceral-dominant disease. Results: Partial response occurred in three of 13 assessable patients (23%; 90% confidence interval, 7% to 49%). All responders had two or fewer sites of metastases. The median time to progression was 4.3 months and the median survival duration was 11.4 months. Patients received a median of seven cycles of therapy (range, two to 21). Severe and/or life-threatening toxicity occurred in 50% and 38%, respectively, and consisted primarily of granulocytopenia, anemia, and neuropathy. The trial was terminated after the first interim analysis as per its two-stage design, since it was unlikely that the response rate would exceed 70%. Conclusion: Biweekly paclitaxel/cisplatin is not likely to produce response rate greater than 70% in patients with metastatic breast cancer who have relapsed after prior doxorubicin-containing adjuvant chemotherapy and who have multiple sites of metastases and/or visceral- dominant disease.