Gemcitabine in combination with doxorubicin in advanced breast cancer:: Final results of a phase II pharmacokinetic trial

Purpose: Gemcitabine has promising single-agent activity in advanced breast disease. The aim of this phase II study was ta determine the efficacy, toxicity, and pharmacokinetic profile of gemcitabine administered with doxorubicin as first-line treatment in patients with metastatic breast cancer. Patients and Methods: Of the 42 women with metastatic breast cancer (age 33 to 74 years; mean age, 55 years), 13 were chemotherapy-naive and 29 had received adjuvant chemotherapy, Gemcitabine (800 or 1,000 mg/m(2)) and doxorubicin (25 mg/m(2)) were administered intravenously on days 1, 8, and 15 of each 28-day cycle. Blood samples were drawn on day 8 of cycles 1, 2, and 3 and of subsequent odd cycles for gemcitabine pharmacokinetic determinations and before and after the first dose of cycle 1 or 2 for doxorubicin determinations. Results: There were three complete and 20 partial responses, for an overall response rate of 55% (95% confidence interval [CI], 40% to 70%) and a complete response rate of 7%, The median survival time for all 42 patients wets 27 months (95% CI, 13.4 to 30.0 months) and the 1-year survival rate was 80%, Toxicity was mainly hematologic. The disposition of both drugs was unchanged when they were administered on the same day compared with when they were given singly. Conclusion: The combination of gemcitabine (800 mg/m(2)) and doxorubicin (25 mg/m(2)) can be safely administered using a weekly schedule. The disposition of both drugs is unchanged when they are administered on the same day. This combination shows promising activity with acceptable toxicity compared with other combination therapies. J Clin Oncol 18:2545-2552. (C) 2000 by American Society of Clinical Oncology.