Dose-escalation study of docetaxel in combination with mitoxantrone as first-line treatment in patients with metastatic breast cancer

Purpose: To define the maximum-tolerated dose (MTD) and the dose-limiting t oxicities (DLTs) of docetaxel in combination with mitoxantrane in patients with metastatic breast cancer (MBC). Patients and Methods: Forty-one chemotherapy-naive patients with MBC (media n age, 61 years) were enrolled. Thirty-eight (93%) had performance status ( World Health Organization [WHO]) 0, 29 (71%) were postmenopausal, and 21 (5 1%) herd estrogen receptor negative tumors. Patients received escalated dos es of docetaxel (75 to 100 mg/m(2)) on day 1 and mitoxantrone (8 to 22 mg/m (2)) on day 8. Treatment was repeated every 3 weeks. Results: A total of 217 chemotherapy cycles were administered. Without reco mbinant human granulocyte colony-stimulating factor (rhG-CSF) support, the MTD1 occurred at the first dose level (docetaxel 75 mg/m(2) and mitoxantron e 8 mg/m(2)); DLTs were febrile neutropenia, grade 4 neutropenia lasting mo re than 5 days, and grade 3 diarrhea. With prophylactic rhG-CSF, the MTD2 w as docetaxel 100 mg/m(2) and mitoxantrone 20 mg/m(2); DLTs were febrile neu tropenia and grade 4 neutropenia. Nine (22%) patients developed neutropenia after the first cycle of treatment. A total of 19 episodes of febrile neut ropenia (9% of the cycles) occurred during the whole period of the study; t here were no toxic deaths. At high docetaxel (100 mg/m(2)) and mitoxantrane (> 12 mg/m(2)) dose levels, a significant decrease of the absolute lymphoc yte number was observed; immunophenotyping revealed that all lymphocyte sub populations were reduced. Grades 2 and 3 neurosensory toxicity occurred in six patients (15%) and one patient (2%), respectively. No cardiac toxicity was observed. Nine complete responses (22%) and 23 partial responses (56%) were achieved (overall response rate, 78%; 95% confidence interval, 62.5% t o 88.8%). The median duration of response was 12.5 months, and the median t ime to tumor progression was 14.5 months. Conclusion: The reported combination of docetaxel and mitoxantrone with G-C SF support is a safe, intensified, well-tolerated, and effective regimen as first-line treatment in patients with MBC. (C) 1999 by American Society of Clinical Oncology.