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Phase I Trial of Pegylated Liposomal Doxorubicin and Docetaxel in Advanced Breast Cancer

From the Albert Einstein Comprehensive Cancer Center, Montefiore Medical Center, Bronx, NY, and Winship Cancer Center, Emory University School of Medicine, Atlanta, GA.

Address reprint requests to Joseph A. Sparano, MD, Albert Einstein Comprehensive Cancer Center, Montefiore Medical Center, Department of Oncology-2 South, Rm 47, 1825 Eastchester Rd, Bronx, NY 10461-2373.

PURPOSE: To develop a combination of pegylated liposomal doxorubicin (Doxil; Alza Pharmaceuticals, Palo Alto, CA) and docetaxel (Taxotere; Aventis Pharmaceutical, Parsipanny, NJ) that can be safely used for the treatment of advanced 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/m² intravenous [IV] infusion over 30 to 60 minutes), followed 1 hour later by docetaxel (60 or 75 mg/m² by IV infusion over 1 hour) in cohorts of three to six patients. Dose-limiting toxicity (DLT) was defined as febrile neutropenia, prolonged neutropenia, or grade 3 to 4 nonhematologic toxicity that occurred during cycle 1.

RESULTS: In conjunction with docetaxel 75 mg/m² every 4 weeks, the MTD of Doxil was 30 mg/m² and required granulocyte colony-stimulating factor (G-CSF) to prevent febrile neutropenia. Without G-CSF, the MTD was docetaxel 60 mg/m² and Doxil 30 mg/m² every 3 weeks; only 1 (7%) out of 15 patients treated at this dose level had cycle 1 DLT. Infusion reactions were common with Doxil with the recommended infusion schedule during the first cycle (55%) but were reduced with a modified schedule (7%). There was no clinically significant cardiac toxicity. Objective response occurred in eight of nine assessable patients with stage III disease and in 16 (52%) of 31 patients (95% confidence interval, 34% to 70%) with stage IV disease.

CONCLUSION: The recommended dose and schedule of this combination for further evaluation is Doxil 30 mg/m² and docetaxel 60 mg/m² given every 3 weeks without G-CSF. When used with G-CSF, it is Doxil 30 mg/m² and docetaxel 75 mg/m² every 4 weeks.

Presented in part at the Twenty-First Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 15, 1998.

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