FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer:: A randomized GERCOR study
FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer:: A randomized GERCOR study
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DOI：
10.1200/jco.2004.05.113
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发表时间：
2004-01-15
影响因子：
45.3
通讯作者：
de Gramont, A
中科院分区：
文献类型：
--
作者：
Tournigand, C;André, T;de Gramont, A
目的在转移性结直肠癌中，III期研究已证明氟尿嘧啶（FU）联合亚叶酸（LV）联合伊立替康或奥沙利铂优于FU + LV单药治疗。这项III期研究研究了两种序列：亚叶酸、FU和伊立替康（FOLFIRI），随后是亚叶酸、FU和奥沙利铂（FOLFOX 6;臂A），和FOLFOX 6，然后FOLFIRI（B组）。患者和方法既往未经治疗的可评估疾病患者随机分配接受2小时输注I-LV 200 mg/m2或dl-LV 400 mg/m2。随后FU推注400 mg/m（2）和46小时输注2，400至3，000 mg/m（2），每46小时一次，每2周一次，第1天与伊立替康180 mg/m（2）或奥沙利铂100 mg/m（2）联合输注2小时。在进展时，伊立替康被奥沙利铂替代（A组），或奥沙利铂被伊立替康替代（B组）。结果109例分配到FOLFIRI然后FOLFOX 6的患者的中位生存期为21.5个月，而111例分配到FOLFOX 6然后FOLFIRI的患者的中位生存期为20.6个月（P = 0.99）。A组的中位第二次无进展生存期（PFS）为14.2个月，而B组为10.9个月（P = 0.64）。在一线治疗中，FOLFIRI达到56%的缓解率（RR）和8.5个月的中位PFS，而FOLFOX 6达到54%的RR和8.0个月的中位PFS（P = 0.26）。二线FOLFIRI达到4% RR和2.5个月中位PFS，而FOLFOX 6达到15% RR和4.2个月PFS。一线治疗中，FOLFIRI组3/4级黏膜炎、恶心/呕吐、2级脱发发生率较高，FOLFOX 6组3/4级中性粒细胞减少和感觉神经毒性发生率较高。结论两种方案均能延长生存期，但疗效相似。毒性特征不同。
Purpose In metastatic colorectal cancer, phase III studies have demonstrated the superiority of fluorouracil (FU) with leucovorin (LV) in combination with irinotecan or oxaliplatin over FU + LV alone. This phase III study investigated two sequences: folinic acid, FU, and irinotecan (FOLFIRI) followed by folinic acid, FU, and oxaliplatin (FOLFOX6; arm A), and FOLFOX6 followed by FOLFIRI (arm B).Patients and Methods Previously untreated patients with assessable disease were randomly assigned to receive a 2-hour infusion of I-LV 200 mg/m(2) or dl-LV 400 mg/m(2) followed by a FU bolus 400 mg/m(2) and 46-hour infusion 2,400 to 3,000 mg/m(2) every 46 hours every 2 weeks, either with irinotecan 180 mg/m(2) or with oxaliplatin 100 mg/m(2) as a 2-hour infusion on day 1. At progression, irinotecan was replaced by oxaliplatin (arm A), or oxaliplatin by irinotecan (arm B).Results Median survival was 21.5 months in 109 patients allocated to FOLFIRI then FOLFOX6 versus 20.6 months in 111 patients allocated to FOLFOX6 then FOLFIRI (P = .99). Median second progression-free survival (PFS) was 14.2 months in arm A versus 10.9 in arm B (P = .64). In first-line therapy, FOLFIRI achieved 56% response rate (RR) and 8.5 months median PFS, versus FOLFOX6 which achieved 54% RR and 8.0 months median PFS (P = .26). Second-line FOLFIRI achieved 4% RR and 2.5 months median PFS, versus FOLFOX6 which achieved 15% RR and 4.2 months PFS. In first-line therapy, National Cancer Institute Common Toxicity Criteria grade 3/4 mucositis, nausea/vomiting, and grade 2 alopecia were more frequent with FOLFIRI, and grade 3/4 neutropenia and neurosensory toxicity were more frequent with FOLFOX6.Conclusion Both sequences achieved a prolonged survival and similar efficacy. The toxicity profiles were different.