Liposomal doxorubicin (M) plus gemcitabine (G) as first line treatment in metastatic breast carcinoma: A phase I-II study

10651 Background: We designed a phase I-II trial to determine the combination dose of liposomal doxorubicin (Myocet) plus gemcitabine (Gemzar), and to evaluate the safety and feasibility of the regimen Methods: Patients with histologically confirmed breast cancer, untreated distant metastasis, age >18 years old, left ventricular ejection fraction (LVEF) >50% and adequate bone marrow, renal and hepatic function were included in the study. Patients received up to six cycles of treatment. No G-CSF support was used prophylactically. LVEF was repeated at 3, and 6 months, and every 6 months thereafter. Results: Phase I: After 6 patients, the recommended dose was M (55 mg/m2) D1 and G (900 mg/m2) D1 and 8, administered every 21 days. Phase II: 53 patients have been enrolled; 52 are included in the safety analysis and 42 in the efficacy analysis. The median age of the population was 61 years of age (32–79). ECOG PS was 0 in 55%, 1 in 41%, 2 in 4%. Postmenopausal status in 87%. Main histology was ductal carcinoma (85%). Prior adjuvant anthracyclines had been administered in 19 cases (median dose of doxorubicin: 300 mg/m2, or epirubicin: 425 mg/m2). Metastasic lesions were in liver (25), lung (17), bone (16), and lymph nodes (25). Patients received a median number of 5 cycles (range 1–6). Median relative dose intensity was 83% for M and 75% for G. Grade III-IV hematologic toxicity per administered cycles was: leukopenia (21.9%), neutropenia (31.2%), febrile neutropenia (4 %), and thrombocytopenia (7.4%). Grade III-IV non-hematologic toxicities were stomatitis (4.8%), nausea (1.7%), vomiting (2.2%), asthenia (2.6%) and diarrhea (0.8%). Thirteen of 52 pts (25%) had alopecia grade III-IV. No signs or symptoms of cardiac impairment have been seen. An objective response rate of 62% was obtained (95% CI: 45.6- 76.4%). Two patients had complete response (4.8%), 24 partial response (57.1%), 10 stable disease and 6 progressive disease. The response rate was similar in patients with or without previous adjuvant anthracyclines (68.5% and 61%, respectively). Conclusions: The combination of liposomal doxorubicin plus gemcitabine has high efficacy and low toxicity in advanced breast cancer patients, and may be a valuable option in patients that have received adjuvant anthracyclines. [Table: see text]