Phase I trial of pegylated liposomal doxorubicin and docetaxel in advancedbreast cancer

Purpose: To develop a combination of pegylated liposomal doxorubicin (Doxil ; Alza Pharmaceuticals, Palo Alto, CA) and docetaxel (Taxotere; Aventis Pha rmaceutical, Parsipanny, NJ) that can be safely used for the treatment of a dvanced breast cancer. Patients and Methods: Forty-one patients with locally advanced (n = 10) or metastatic (n = 31) breast cancer received Doxil (30-, 40-, or 45-mg/m(2) i ntravenous [IV] infusion over 30 to 60 minutes), followed 1 hour later by d ocetaxel (60 or 75 mg/m(2) by IV infusion over 1 hour) in cohorts of three to six patients. Dose-limiting toxicity (DLT) was defined as febrile neutro penia, prolonged neutropenia, or grade 3 to 4 nonhematologic toxicity that occurred during cycle 1. Results: In conjunction with docetaxel 75 mg/m(2) every 4 weeks, the MTD of Doxil wets 30 mg/m(2) and required granulocyte colony-stimulating factor ( G-CSF) to prevent febrile neutropenia. Without G-CSF, the MTD wets docetaxe l 60 mg/m(2) and Doxil 30 mg/m(2) every 3 weeks; only 1 (7%) out of 15 pati ents treated at this dose level had cycle 1 DLT. infusion reactions were co mmon with Doxil with the recommended infusion schedule during the first cyc le (55%) but were reduced with a modified schedule (7%), There was no clini cally significant cardiac toxicity, Objective response occurred in eight of nine assessable patients with stage III disease and in 16 (52%) of 31 pati ents (95% confidence interval, 34% to 70%) with stage IV disease, Conclusion: The recommended dose and schedule of this combination for furth er evaluation is Doxil 30 mg/m(2) and docetaxel 60 mg/m(2) given every 3 we eks without G-CSF. When used with G-CSF, it is Doxil 30 mg/m(2) and docetax el 75 mg/m2 every 4 weeks. J Clin Oncol 19:3111-3125. (C) 2001 by American Society of Clinical Oncology.