A multicenter phase II study of FOLFIRI as first-line chemotherapy for metastatic colorectal cancer with reduced starting dose of irinotecan in patients with homozygous for UGT1A1(FLIGHT1)

Interventions: On Day 1, patients treated with FOLFIRI therapy received a 2-hour intravenous infusion of CPT-11 (150 mg/m2) combined with 1-LV (200 mg/m2), followed by a rapid intravenous infusion of 5-FU (400 mg/m2), and then a 46-hour continuous infusion of 5-FU (2,400 mg/m2). This regimen comprised one course of therapy and was repeated once every 2 weeks. Cycles of treatment will be continued for this study until disease progression (PD) occurs. Patients will undergo UGT1A1 genotyping before starting to receive the protocol treatment. As recommended in the US prescribing information for Camptosar;, the starting dose of CPT-11 will be reduced to 100 mg/m2 in patients who are homozygous for the *28 allelic variant of UGT1A1 (further reduced to 75 mg/m2 in such patients aged 76-80 years). No dose adjustments will be made in patients who undergo UGT1A1 genotyping after starting to receive the protocol treatment.
Primary outcome(s): (1)response rate (2)incidence and severity of adverse events
Study Design: Single arm Non-randomized

干预措施：第1天，接受FOLFIRI疗法（FOLFIRI）的患者将接受时长2小时的伊立替康（CPT-11，150 mg/m²）静脉输注，联合亚叶酸钙（1-LV，200 mg/m²）；随后快速静脉推注氟尿嘧啶（5-FU，400 mg/m²），再进行时长46小时的持续静脉输注氟尿嘧啶（5-FU，2400 mg/m²）。该方案为1个治疗周期，每2周重复1次。本研究将持续进行治疗周期，直至患者出现疾病进展（PD）。患者在开始接受方案治疗前需完成UGT1A1基因分型（UGT1A1 genotyping）。参照美国开普拓（Camptosar）的处方说明书建议，对于UGT1A1 *28等位变异体纯合子患者，伊立替康（CPT-11）的起始剂量将降至100 mg/m²；对于年龄76~80岁的此类患者，起始剂量将进一步降至75 mg/m²。对于在开始接受方案治疗后才进行UGT1A1基因分型的患者，无需调整给药剂量。主要结局指标：(1) 缓解率；(2) 不良事件的发生率与严重程度。研究设计：单臂非随机化研究