[A Phase I Combination Dose-Escalation Study of Eribulin Mesylate and Gemcitabine in Japanese Patients with Metastatic Breast Cancer].

Although eribulin mesylate(ERI)has been approved for metastatic breast cancer, its efficacy and safety in combination with other chemotherapeutic agents have not been established. To investigate the tolerability of combination therapy with ERI and gemcitabine(GEM), we conducted a phase I clinical study in Japanese patients with metastatic breast cancer. The initial doses(Level 0)of ERI and GEM were 1.1mg/m2 and 800 mg/m2, respectively. When tolerability to Level 0 doses was confirmed, the doses were escalated to 1.4mg/m2 for ERI and 800 mg/m2 for GEM(Level 1). Seven patients were enrolled in this study; 3 patients received Level 0 doses and the other 4 patients received Level 1 doses. A dose limiting toxicity(DLT)was found in only 1 patient of the Level 1 group(Grade 3 oral mucositis). However, Grade 3 or higher hematological toxicities, including neutropenia, frequently occurred, and hence, this combination therapy was not conducted as scheduled. Thus, maximum tolerated dose(MTD)and recommended dose(RD)for phase II trials were not evaluated in this study. Drugdrug interactions between ERI and GEM were not observed. In conclusion, it was difficult to continue the combination therapy for patients with advanced recurrent breast cancer due to hematological toxicities. There is little possibility for the combination therapy with ERI and GEM at the specific doses to be regarded as a new treatment option for Japanese patients.