Phase I Study of Fixed Dose Gemcitabine Plus Epirubicin in Patients With Advanced Solid Malignancies

Objectives: A Phase I study was initiated to investigate fixed dose rate gemcitabine (GEM) combined with epirubicin (EPI) given weekly or every other week, since, GEM given as a standard 30 minute infusion has modest activity. The study was designed based on the hypothesis that prolonged exposure (over 90 minutes) may improve response rates and combination with epirubicin (EPI) is synergistic. Methods: Eligible patients had measurable refractory solid malignancies with adequate bone marrow, renal, and liver functions. Patients received GEM 800, 1000, 1250 mg/m(2) over 90 minutes followed by EPI 10 or 15 mg/m(2) as a 30 minutes infusion on days 1, 8, and 15 or days 1 and 15 of a 28 day cycle. Results: Twenty-eight patients were enrolled and 24 are evaluable for overall toxicities and response rate. Toxicities include neutropenia (Gr 3 of Gr 4, 9 pts), thrombocytopenia (Gr 3 of Gr 4, 3 pts), fatigue (Gr 3 of Gr 4, 4 pts), and myalgia (Gr 3 of Gr 4, 1 pt). Dose limiting toxicity was grade 4 neutropenia. Seven patients experienced stable disease for > 16 weeks and 3 patients with pancreatic cancer had partial responses. Conclusions: The maximum tolerated dose is GEM 800 mg/m(2)/EPI 10 mg/m(2) days 1, 8, 15 or GEM 1000 mg/m(2)/EPI 15 mg/m(2) days 1, 15 given every 4 weeks. Further studies are warranted with targeted therapies to define the efficacy of this doublet.