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.22.02774
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发表时间：
2023-07
影响因子：
45.3
通讯作者：
C. Tournigand;T. André;E. Achille;G. Lledo;M. Flesh;D. Mery-mignard;E. Quinaux;C. Couteau;M. Buyse;G. Ganem;B. Landi;P. Colin;C. Louvet;A. de Gramont
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文献类型：
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作者：
C. Tournigand;T. André;E. Achille;G. Lledo;M. Flesh;D. Mery-mignard;E. Quinaux;C. Couteau;M. Buyse;G. Ganem;B. Landi;P. Colin;C. Louvet;A. de Gramont
目的：在转移性结直肠癌中，III期研究已经证明氟尿嘧啶（FU）与亚叶酸钙（LV）联合伊立替康或奥沙利铂优于FU + LV。这项III期研究调查了两个序列：叶酸、FU和伊立替康（FOLFIRI），然后是叶酸、FU和奥沙利铂（FOLFOX6， A组），FOLFOX6，然后是FOLFIRI （B组）。患者和方法先前未经治疗的可评估疾病的患者随机分配接受2小时输注l-LV 200 mg/m2或dl-LV 400 mg/m2，然后每2周每46小时输注400 mg/m2至3000 mg/m2 46小时，伊立替康180 mg/m2或奥沙利铂100 mg/m2作为2小时输注。在进展阶段，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例患者中位生存期为21.5个月，分别接受FOLFIRI和FOLFOX6治疗，111例患者中位生存期为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FOLFOX6达到54%的RR和8.0个月的中位PFS （P = 0.26）。二线FOLFIRI达到4%的RR和2.5个月的中位PFS，而FOLFOX6达到15%的RR和4.2个月的PFS。在一线治疗中，国家癌症研究所共同毒性标准3/4级粘膜炎、恶心/呕吐和2级脱发在FOLFIRI中更常见，3/4级中性粒细胞减少和神经感觉毒性在FOLFOX6中更常见。结论两种治疗方案均获得了较长的生存期和相似的疗效。毒性谱是不同的。
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 l-LV 200 mg/m2 or dl-LV 400 mg/m2 followed by a FU bolus 400 mg/m2 and 46-hour infusion 2,400 to 3,000 mg/m2 every 46 hours every 2 weeks, either with irinotecan 180 mg/m2 or with oxaliplatin 100 mg/m2 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.