A PHASE-II TRIAL OF CIRCADIAN-TIMED PACLITAXEL AND CISPLATIN THERAPY IN METASTATIC BREAST-CANCER

Purpose: In a phase II study with combination paclitaxel and cisplatin in metastatic breast cancer using circadian timing, we attempted to m aximise response and minimise toxicity. Materials and methods: Forty-o ne patients with histologically-proven metastatic breast cancer with o r without previous chemotherapy were treated with Paclitaxel 135 mg/m( 2) administered as a three-hour infusion at 06.00 hours followed by ci splatin 75 mg/m(2) as a one-hour infusion at 18.00 hours utilising cir cadian timing. Six cycles were planned once every 21 days. Response as sessment was performed every two cycles, and toxicity was measured usi ng 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% conf idence interval (CI) 69-92). Responses were seen in patients previousl y treated with anthracyclines (75%) (95% CI 57-92), and in patients wh o 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 (ra nge 3-26, 95% CI 5.0-9.8), and 14 of the responses (42%), (95% CI 28-6 2) were durable. A total of 212 cycles of chemotherapy were given. The re were 15 episodes (7%) of grade 3-4 neutropenia, seven (3.2%) of gra de 3-4 neurologic toxicity, and three (1.4%) of grade 3-4 nephrotoxici ty. There were no toxic deaths. Conclusion: The combination of paclita xel and cisplatin is very effective in metastatic breast cancer, and w ith application of circadian timing, toxicity has been acceptable. Thi s combination is being tested as primary therapy in locally-advanced b reast cancer at our institution.