A phase II trial of circadian-timed paclitaxel and cisplatin therapy in metastatic breast cancer

Abstract

Purpose: In a phase II study with combination paclitaxel and cisplatin in metastatic breast cancer using circadian timing, we attempted to maximise response and minimise toxicity. Materials and methods: Forty-one patients with histologitally-proven metastatic breast cancer with or without previous chemotherapy were treated with Paclitaxel 135 mg/m2 administered as a three- hour infusion at 06.00 hours followed by cisplatin 75 mg/m2 as a one-hour infusion at 18.00 hours utilising circadian timing. Six cycles were planned once every 21 days. Response assessment was performed every two cycles, and toxicity was measured using WHO criteria. Results: All patients were evaluable for response and toxicity. There were nine (22%) complete responses (CR), and 24 (59%) partial responses (PR), for an overall response rate of 80% (95% confidence interval (CI) 69-92). Responses were seen in patients previously treated with anthracyclines (75%) (95% CI 57-92), and in patients who had had no prior chemotherapy (90%) (95% CI 71-100). Responses were seen in all metastatic sites: liver 80%, lung 76%, bone 69%, and soft tissues 71%. The overall median response duration was seven months (range 3-26, 95% CI 5.0-9.8), and 14 of the responses (42%), (95% CI 28-62) were durable. A total of 212 cycles of chemotherapy were given. There were 15 episodes (7%) of grade 3-4 neutropenia, seven (3.2%) of grade 3-4 neurologic toxicity, and three (1.4%) of grade 3-4 nephrotoxicity. There were no toxic deaths. Conclusion: The combination of paclitaxel and cisplatin is very effective in metastatic breast cancer, and with application of circadian timing, toxicity has been acceptable. This combination is being tested as primary therapy in locally-advanced breast cancer at our institution.