Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
Department of Medical Oncology, Ishikawa Prefectural Central Hospital, 2-1, Kuratsuki-higashi, Kanazawa, Ishikawa, 920-8530, Japan.
Cancer Chemother Pharmacol. 2020 Aug;86(2):277-284. doi: 10.1007/s00280-020-04116-x. Epub 2020 Jul 24.
Ramucirumab, an anti-vascular endothelial growth factor (VEGF) receptor2 monoclonal antibody, inhibits VEGF-A, VEGF-C, and VEGF-D binding and endothelial cell proliferation. We conducted a phase Ib study to determine the recommended phase II dose (RP2D) of fluorouracil, l-leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus ramucirumab.
This phase Ib study investigated three dose levels of FOLFOXIRI plus ramucirumab (three dose levels of irinotecan and fluorouracil with fixed dose of oxaliplatin 85 mg/m and ramucirumab 8 mg/kg on day 1, repeated every 2 weeks) in chemotherapy-naïve patients with metastatic colorectal cancer (mCRC). Dose-limiting toxicity (DLT) was assessed during the first cycle.
A total of ten patients were enrolled. The first four patients received the treatment at dose level 0 (irinotecan 150 mg/m and fluorouracil 2400 mg/m), and subsequent six patients were treated at dose level 1 (irinotecan 165 mg/m and fluorouracil 3200 mg/m). No DLT was observed in the nine DLT-evaluable patients, which indicated that the RP2D was dose level 1. Grade 3 or worse adverse events included neutropenia (70%), hypertension (20%), and febrile neutropenia (10%). No treatment-related death was observed in any cycle. The overall response rate was 70%.
The RP2D of FOLFOXIRI plus ramucirumab was determined to be 8 mg/kg of ramucirumab, 165 mg/m of irinotecan, 85 mg/m of oxaliplatin, 200 mg/m of l-leucovorin, and 3200 mg/m of fluorouracil.
UMIN000023277.
雷莫芦单抗（一种抗血管内皮生长因子 [VEGF] 受体 2 单克隆抗体）可抑制 VEGF-A、VEGF-C 和 VEGF-D 的结合以及内皮细胞的增殖。我们开展了一项 Ib 期研究，以确定氟尿嘧啶、左亚叶酸钙、奥沙利铂和伊立替康（FOLFOXIRI）联合雷莫芦单抗的推荐 II 期剂量（RP2D）。
这项 Ib 期研究在未经化疗的转移性结直肠癌（mCRC）患者中，评估了三个剂量水平的 FOLFOXIRI 联合雷莫芦单抗（三个剂量水平的伊立替康和氟尿嘧啶，联合奥沙利铂 85mg/m2 和雷莫芦单抗 8mg/kg，第 1 天给药，每 2 周重复一次）。在第 1 个周期中评估剂量限制性毒性（DLT）。
共纳入 10 例患者。前 4 例患者接受了剂量水平 0（伊立替康 150mg/m2 和氟尿嘧啶 2400mg/m2）的治疗，随后 6 例患者接受了剂量水平 1（伊立替康 165mg/m2 和氟尿嘧啶 3200mg/m2）的治疗。在 9 例可评估 DLT 的患者中，未观察到 DLT，表明 RP2D 为剂量水平 1。3 级或更高级别的不良事件包括中性粒细胞减少症（70%）、高血压（20%）和发热性中性粒细胞减少症（10%）。在任何周期均未观察到与治疗相关的死亡。总体缓解率为 70%。
FOLFOXIRI 联合雷莫芦单抗的 RP2D 确定为雷莫芦单抗 8mg/kg、伊立替康 165mg/m2、奥沙利铂 85mg/m2、左亚叶酸钙 200mg/m2 和氟尿嘧啶 3200mg/m2。
UMIN000023277。
