PURPOSE: This study was conducted to determine, in patients with advanced-stage breast cancer, the maximum tolerated dose (MTD) of capecitabine administered orally for 7 days followed by a 7-day rest (7/7), a schedule based on a mathematical method for the optimization of anticancer drug scheduling. PATIENTS AND METHODS: Eligible patients had measurable, metastatic breast cancer. There was no limit to number of prior treatments. A standard, three-patients-per-cohort dose-escalation scheme used flat-dose capecitabine beginning at 1,500 mg orally twice daily (bid) on a 7/7 schedule. Each cohort was monitored for 28 days before escalation to the next cohort to assess for delayed toxicity. Response was evaluated radiographically every 12 weeks; toxicity was assessed every 2 weeks. RESULTS: Twenty-one patients were treated on study. The most frequently reported treatment-related grade 2/3 adverse events were hand-foot syndrome (29%), leukopenia/neutropenia (24%), and fatigue (19%). Grade 3 toxicity was transient and easily managed. Three patients experienced grade 3 hand-foot syndrome; one of these patients had grade 3 diarrhea. There were no grade 4 events. The MTD of capecitabine 7/7 is 2,000 mg twice daily. CONCLUSION: As predicted by mathematical modeling, capecitabine dosing for 7 days followed by a 7-day rest is well tolerated. Efficacy of this schedule is being determined in a phase II clinical trial in patients with advanced breast cancer.
PURPOSE: This study was conducted to determine, in patients with advanced-stage breast cancer, the maximum tolerated dose (MTD) of capecitabine administered orally for 7 days followed by a 7-day rest (7/7), a schedule based on a mathematical method for the optimization of anticancer drug scheduling. PATIENTS AND METHODS: Eligible patients had measurable, metastatic breast cancer. There was no limit to number of prior treatments. A standard, three-patients-per-cohort dose-escalation scheme used flat-dose capecitabine beginning at 1,500 mg orally twice daily (bid) on a 7/7 schedule. Each cohort was monitored for 28 days before escalation to the next cohort to assess for delayed toxicity. Response was evaluated radiographically every 12 weeks; toxicity was assessed every 2 weeks. RESULTS: Twenty-one patients were treated on study. The most frequently reported treatment-related grade 2/3 adverse events were hand-foot syndrome (29%), leukopenia/neutropenia (24%), and fatigue (19%). Grade 3 toxicity was transient and easily managed. Three patients experienced grade 3 hand-foot syndrome; one of these patients had grade 3 diarrhea. There were no grade 4 events. The MTD of capecitabine 7/7 is 2,000 mg twice daily. CONCLUSION: As predicted by mathematical modeling, capecitabine dosing for 7 days followed by a 7-day rest is well tolerated. Efficacy of this schedule is being determined in a phase II clinical trial in patients with advanced breast cancer.
Authors: Aki Morikawa; Elisa de Stanchina; Elena Pentsova; Margaret M Kemeny; Bob T Li; Kendrick Tang; Sujata Patil; Martin Fleisher; Catherine Van Poznak; Larry Norton; Andrew D Seidman Journal: Clin Cancer Res Date: 2019-04-15 Impact factor: 12.531
Authors: E L Mayer; A H Partridge; L N Harris; R S Gelman; S T Schumer; H J Burstein; E P Winer Journal: Breast Cancer Res Treat Date: 2009-03-18 Impact factor: 4.872
Authors: Michelle A Rudek; Roisin M Connolly; Janelle M Hoskins; Elizabeth Garrett-Mayer; Stacie C Jeter; Deborah K Armstrong; John H Fetting; Vered Stearns; Laurie A Wright; Ming Zhao; Stanley P Watkins; Howard L McLeod; Nancy E Davidson; Antonio C Wolff Journal: Breast Cancer Res Treat Date: 2013-04-16 Impact factor: 4.872
Authors: P García-Alfonso; A J Muñoz-Martin; S Alvarez-Suarez; Y Jerez-Gilarranz; M Riesco-Martinez; P Khosravi; M Martin Journal: Br J Cancer Date: 2010-10-26 Impact factor: 7.640
Authors: E Vasile; G Masi; L Fornaro; S Cupini; F Loupakis; S Bursi; I Petrini; S Di Donato; I M Brunetti; S Ricci; A Antonuzzo; S Chiara; D Amoroso; M Andreuccetti; A Falcone Journal: Br J Cancer Date: 2009-05-12 Impact factor: 7.640