title: A phase II trial of circadian-timed paclitaxel and cisplatin therapy in metastatic breast cancer.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Forty-one patients with histologically-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Oncology Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia.
authors.forename: A
authors.initials: A
authors.lastname: Ezzat
authors.forename: M A
authors.initials: MA
authors.lastname: Raja
authors.forename: J
authors.initials: J
authors.lastname: Berry
authors.forename: S
authors.initials: S
authors.lastname: Bazarbashi
authors.forename: F
authors.initials: F
authors.lastname: Zwaan
authors.forename: M
authors.initials: M
authors.lastname: Rahal
authors.forename: A
authors.initials: A
authors.lastname: el-Warith
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000627:therapeutic use; D011446:Prospective Studies; D012074:Remission Induction; D016019:Survival Analysis
chemical_list: D017239:Paclitaxel; D002945:Cisplatin