Phase II trial combining paclitaxel with 24-hour infusion cisplatin for chemotherapy-naïve patients with locally advanced or metastatic breast carcinoma

BACKGROUND. Both paclitaxel and cisplatin are active as second-line chemotherapy for patients with breast carcinoma. A synergistic cytotoxicity of these two drugs has been demonstrated in vitro. This study sought to determine the efficacy of combining these two drugs in the treatment of chemotherapy-naïve patients with breast carcinoma. METHODS. The inclusion criteria for the study were 1) women with histologically proven breast carcinoma; 2) locally advanced disease, as defined by American Joint Committee on Cancer (AJCC) Stage T4 (locally advanced breast carcinoma [LABC]) or clinically proven metastases (metastatic breast carcinoma [MBC]); and 3) no prior cytotoxic chemotherapy. The regimen consisted of paclitaxel 175 mg/m² intravenously by 3-hour infusion immediately followed by cisplatin 50 mg/m² intravenously by 24-hour infusion on Day 1 and repeated every 3 weeks. After a maximal response to chemotherapy was achieved, patients with LABC underwent resection of their primary tumor if the procedure was not contraindicated. RESULTS. From July, 1999 to January, 2001, 46 patients were enrolled into this study (28 patients with LABC and 18 patients with MBC). Their median age was 49.5 years (range, 29.8-65.5 years). A total of 205 cycles of chemotherapy were given. All patients were evaluable for toxicity, and 45 patients were evaluable for response. There were 3 complete responses (CRs) and 24 partial responses (PRs), for an overall response rate of 58.7% (95% confidence interval, 44.5-72.9%). Grade 4 hypersensitivity (asthma) to paclitaxel occurred in one patient. Grade 3-4 nausea and emesis and Grade 3-4 myelosuppression occurred in six patients and four patients, respectively. Of the 28 patients with LABC, 2 patients achieved a CR, and 14 patients achieved a PR. Twenty-seven patients underwent mastectomy patients after chemotherapy. A pathologic CR was documented in one patient. Postoperatively, 23 patients with LABC received adjuvant chemotherapy, and 18 patients with LABC received adjuvant radiotherapy. During a median follow-up of 14.6 months, 5 of 28 patients with LABC developed recurrent disease, and 2 patients died of progressive disease, whereas 3 of 18 patients with MBC died of progressive disease. CONCLUSIONS. The combination of paclitaxel by 3-hour infusion and cisplatin by 24-hour infusion appears to be an active and well-tolerated regimen for chemotherapy-naïve patients with LABC or MBC.