Phase I study of stealth liposomal doxorubicin in combination with gemcitabine in the treatment of patients with metastatic breast cancer

Purpose: We conducted a single-institution phase I clinical trial to determ ine the maximum-tolerated dose (MTD) and define the toxic effects of stealt h liposomal doxorubicin in combination with gemcitabine in patients with me tastatic breast cancer. Patients and Methods: Patients were eligible if they had disease progressio n with no limit on prior number of chemotherapy regimens. Prior treatment w ith liposomal doxorubicin and/or gemcitabine was not allowed. The starting dose of liposomal doxorubicin was 20 mg/m(2) on day 1 only with a 20% dose escalation of the previous mg/m(2) dose until MTD was reached. Gemcitabine was given as a fixed dose of 800 mg/m(2) on days 1 and 8 every 3 weeks. Results: We treated 27 patients of whom six had never received chemotherapy for their disease. Most had had visceral involvement as their dominant sit e of disease. The dose-limiting toxicity was myelosuppression, which includ ed neutropenia and thrombocytopenia. However, neither neutropenic fever nor episodes of bleeding were major occurrences. Significant antitumor activit y was also observed with a total of two complete and seven partial response s. the recommended phase II dose is liposomal doxorubicin 24 mg/m(2) on day 1 and gemcitabine 800 mg/m(2) on days 1 and 8 every 21 days. Conclusion: The combination of liposomal doxorubicin and gemcitabine is an active and well tolerated regimen when administered on a 21-day schedule. M yelo-suppression limited further dose escalation, however, it did not incre ase the incidence of neutropenic fever. Significant antitumor activity seen in heavily and minimally pretreated patients warrants further evaluation o f this combination. (C) 2001 by American Society of Clinical Oncology.