GEMCITABINE PLUS DOSE-ESCALATED EPIRUBICIN IN ADVANCED BREAST-CANCER - RESULTS OF A PHASE-I STUDY

Gemcitabine has shown single-agent activity in metastatic breast cance r. Epirubicin is also widely used for the adjuvant and treatment of me tastatic breast cancer. The toxicity profiles and modes of action are different which provides a good rationale for studying both drugs in c ombination. In a phase I study gemcitabine at a fixed dose of 1000 mg/ m(2) on days 1, 8, 15 of a 28 day cycle was combined with escalated we ekly doses of epirubicin starting with an initial dose of 10 mg/m(2). Patients had stage IV metastatic disease without previous chemotherapy except as adjuvant treatment. Nineteen patients were included in the study which defined the maximum tolerated dose (MTD) of epirubicin at 20 mg/m(2). Myelosuppression was the dose limiting toxicity with leuco penia WHO grade 3 and 4 in 40.0% and 20.0%, neutropenia WHO grade 3 an d 4 without neutropenic fever in 20.0% and 40.0% and thrombocytopenia WHO grade 3 in 20.0%. At the epirubicin 15 mg/m(2) dose level, leucope nia (11.1% WHO grade 3) and neutropenia (12.5 and 37.5% WHO grade 3 an d 4) were reported. Symptomatic toxicity was generally mild: nausea/vo miting in about 20% of patients (WHO grade 3 or 4) on both 15 and 20 m g/m(2) epirubicin dose levels. Alopecia WHO grade 3 and 3 was seen in ? patients at MTD. Four of 19 evaluable patients had a partial respons e. We conclude that the combination of gemcitabine and epirubicin is w ell tolerated and has promising activity. A phase II study is underway with gemcitabine 1000 mg/m(2) and epirubicin 15 mg/m(2) on days 1, 8 and 15 of a 28 day cycle.