Yoshino Takayuki, Yamazaki Kentaro, Gotoh Masahiro, Nasroulah Federico, Gao Ling, Yoshizuka Naoto, Ohtsu Atsushi
National Cancer Center Hospital East, Kashiwa, Japan
Shizuoka Cancer Center, Shizuoka, Japan.
Anticancer Res. 2015 Jul;35(7):4003-7.
This phase Ib study evaluated the pharmacokinetic profile and safety of ramucirumab, a recombinant human IgG1 neutralizing monoclonal antibody specific for vascular endothelial growth factor receptor 2, in combination with irinotecan, levofolinate and 5-fluorouracil (FOLFIRI) in Japanese patients with metastatic colorectal carcinoma (mCRC).
Eligible patients had Eastern Cooperative Oncology Group performance status 0-1, and disease progression during or within 6 months following first-line therapy with bevacizumab, oxaliplatin and a fluoropyrimidine. Six enrolled patients received 8 mg/kg ramucirumab plus FOLFIRI every 2 weeks.
One out of six patients experienced a dose-limiting toxicity (grade 2 proteinuria and grade 4 neutropenia, resulting in a dose delay >2 weeks). All patients experienced at least one grade 3 or higher adverse event: neutropenia (five patients, 83%), proteinuria (two patients; 33%) and anemia, thrombocytopenia and hypertension (one patient each, 17%). There were no serious adverse events or deaths.
Ramucirumab plus FOLFIRI was well-tolerated in Japanese patients with mCRC, warranting further investigation of this combination therapy.
本 Ib 期研究评估了雷莫西尤单抗（一种重组人 IgG1 血管内皮生长因子受体 2 特异性中和单克隆抗体）与伊立替康、亚叶酸钙和 5-氟尿嘧啶（FOLFIRI）联合应用于日本转移性结直肠癌（mCRC）患者的药代动力学特征和安全性。
符合条件的患者东部肿瘤协作组体能状态为 0 - 1，且在一线使用贝伐单抗、奥沙利铂和氟嘧啶治疗期间或治疗后 6 个月内疾病进展。6 名入组患者每 2 周接受 8mg/kg 雷莫西尤单抗加 FOLFIRI 治疗。
6 名患者中有 1 名出现剂量限制性毒性（2 级蛋白尿和 4 级中性粒细胞减少，导致剂量延迟>2 周）。所有患者均经历至少一次 3 级或更高等级的不良事件：中性粒细胞减少（5 名患者，83%）、蛋白尿（2 名患者；33%）以及贫血、血小板减少和高血压（各 1 名患者，17%）。未出现严重不良事件或死亡。
雷莫西尤单抗加 FOLFIRI 在日本 mCRC 患者中耐受性良好，值得对这种联合治疗进行进一步研究。
