A phase II study of paclitaxel/cisplatin combination in patients with metastatic breast cancer refractory to anthracycline-based chemotherapy

Aims and background: To investigate the safety and efficacy of a paclitaxel and cisplatin regimen in a selected group of metastatic breast cancer patients with primary or acquired chemoresistance to anthracycline-based chemotherapy. Patients and methods: Thirty-eight consecutive women with metastatic breast cancer (PS less than or equal to 2) were entered in this phase II trial; all patients had been previously treated for metastatic disease with chemotherapy containing anthracyclines and had shown a progression of the disease during drug administration or after a clinical response lasting less than 6 months. Fifteen patients had received 2 or more chemotherapeutic regimens for advanced disease; 31 patients had greater than or equal to 2 sites of metastatic disease. Paclitaxel (135 mg/m(2)) was administered iv by a 3-hr infusion followed by iv infusion of cisplatin (75 mg/m(2)) on day 1, every 3 weeks for 6 cycles, After the completion of the planned chemotherapy administration, 9 responsive patients continued to receive paclitaxel alone (175 mg/m(2)) iv, on day 1, every 3 weeks, until disease progression or unacceptable toxicity. Results: A partial clinical response was recorded in 17 cases (45%; 95% CI, 30-64%), The median duration of overall response was 8 months; for the 9 responsive patients who continued treatment with paclitaxel alone, 4 had maintained the partial clinical response at the median follow-up of 24 months from the onset of therapy. The median time to progression was 6 months and median overall survival 8 months. Neurotoxicity was the most frequent adverse effect and caused treatment discontinuation in 5 cases for grade 3-4 paresthesia and/or an arthralgia/myalgia syndrome. Grade 3-4 neutropenia occurred in 16 patients (44%). Conclusions: Paclitaxel/cisplatin is an active regimen for the treatment of patients with metastatic breast cancer refractory to anthracycline-based chemotherapy. However, the cumulative neurotoxicity should limit the efficacy of prolonged paclitaxel monotherapy in responsive patients.