Kondo Naoto, Kashiwaba Masahiro, Goto Risa, Hattori Masaya, Iwata Hiroji
Dept. of Breast and Endocrine Surgery, Nagoya City University Hospital.
Gan To Kagaku Ryoho. 2018 Aug;45(8):1165-1170.
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.
尽管甲磺酸艾瑞布林（ERI）已被批准用于治疗转移性乳腺癌，但其与其他化疗药物联合使用时的疗效和安全性尚未确定。为了研究ERI与吉西他滨（GEM）联合治疗的耐受性，我们在日本转移性乳腺癌患者中开展了一项I期临床研究。ERI和GEM的初始剂量（0级）分别为1.1mg/m²和800mg/m²。当确认对0级剂量耐受时，剂量分别增加至ERI 1.4mg/m²和GEM 800mg/m²（1级）。本研究共纳入7例患者；3例接受0级剂量，另外4例接受1级剂量。仅在1级组的1例患者中发现了剂量限制性毒性（DLT）（3级口腔黏膜炎）。然而，3级或更高等级的血液学毒性，包括中性粒细胞减少症，频繁发生，因此，该联合治疗未按计划进行。因此，本研究未评估II期试验的最大耐受剂量（MTD）和推荐剂量（RD）。未观察到ERI与GEM之间的药物相互作用。总之，由于血液学毒性，晚期复发性乳腺癌患者难以继续进行联合治疗。对于日本患者而言，特定剂量的ERI与GEM联合治疗几乎不可能被视为一种新的治疗选择。
