氟尿嘧啶持续输注、亚叶酸钙、奥沙利铂和伊立替康（FOLFOXIRI）与氟尿嘧啶持续输注、亚叶酸钙和伊立替康（FOLFIRI）用于转移性结直肠癌一线治疗的III期试验：西北肿瘤协作组

Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest.

作者信息

Falcone Alfredo, Ricci Sergio, Brunetti Isa, Pfanner Elisabetta, Allegrini Giacomo, Barbara Cecilia, Crinò Lucio, Benedetti Giovanni, Evangelista Walter, Fanchini Laura, Cortesi Enrico, Picone Vincenzo, Vitello Stefano, Chiara Silvana, Granetto Cristina, Porcile Gianfranco, Fioretto Luisa, Orlandini Cinzia, Andreuccetti Michele, Masi Gianluca

机构信息

U.O. Oncologia Medica, Istituto Toscano Tumori, Livorno, Italy.

出版信息

J Clin Oncol. 2007 May 1;25(13):1670-6. doi: 10.1200/JCO.2006.09.0928.

DOI:10.1200/JCO.2006.09.0928

PMID:17470860

Abstract

PURPOSE

The Gruppo Oncologico Nord Ovest (GONO) conducted a phase III study comparing fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI [irinotecan 165 mg/m2 day 1, oxaliplatin 85 mg/m2 day 1, leucovorin 200 mg/m2 day 1, fluorouracil 3,200 mg/m2 48-hour continuous infusion starting on day 1, every 2 weeks]) with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI).

METHODS

Selection criteria included unresectable metastatic colorectal cancer, age 18 to 75 years, and no prior chemotherapy for advanced disease. The primary end point was response rate (RR).

RESULTS

A total of 244 patients were randomly assigned. An increase of grade 2 to 3 peripheral neurotoxicity (0% v 19%; P < .001), and grade 3 to 4 neutropenia (28% v 50%; P < .001) were observed in the FOLFOXIRI arm. The incidence of febrile neutropenia (3% v 5%) and grade 3 to 4 diarrhea (12% v 20%) were not significantly different. Responses, as assessed by investigators, were, for FOLFIRI and FOLFOXIRI, respectively, complete, 6% and 8%; and partial, 35% and 58%, (RR, 41% v 66%; P = .0002). RR confirmed by an external panel was 34% versus 60% (P < .0001). The R0 secondary resection rate of metastases was greater in the FOLFOXIRI arm (6% v 15%; P = .033, among all 244 patients; and 12% v 36%; P = .017 among patients with liver metastases only). Progression-free survival (PFS) and overall survival (OS) were both significantly improved in the FOLFOXIRI arm (median PFS, 6.9 v 9.8 months; hazard ratio [HR], 0.63; P = .0006; median OS, 16.7 v 22.6 months; HR, 0.70; P = .032).

CONCLUSION

The FOLFOXIRI regimen improves RR, PFS, and OS compared with FOLFIRI, with an increased, but manageable, toxicity in patients with metastatic colorectal cancer with favorable prognostic characteristics. Further studies of FOLFOXIRI in combination with targeted agents and in the neoadjuvant setting are warranted.

摘要

目的

西北肿瘤协作组（GONO）开展了一项III期研究，比较氟尿嘧啶、亚叶酸钙、奥沙利铂和伊立替康（FOLFOXIRI[伊立替康165mg/m²第1天，奥沙利铂85mg/m²第1天，亚叶酸钙200mg/m²第1天，氟尿嘧啶3200mg/m²从第1天开始48小时持续输注，每2周一次]）与氟尿嘧啶、亚叶酸钙和伊立替康持续输注方案（FOLFIRI）。

方法

入选标准包括不可切除的转移性结直肠癌、年龄18至75岁且既往未接受过晚期疾病的化疗。主要终点为缓解率（RR）。

结果

共244例患者被随机分组。FOLFOXIRI组观察到2至3级外周神经毒性增加（0%对19%；P<.001），以及3至4级中性粒细胞减少（28%对50%；P<.001）。发热性中性粒细胞减少的发生率（3%对5%）和3至4级腹泻（12%对20%）无显著差异。经研究者评估，FOLFIRI组和FOLFOXIRI组的缓解情况分别为：完全缓解，6%和8%；部分缓解，35%和58%，（RR，41%对66%；P=.0002）。外部专家小组确认的RR为34%对60%（P<.0001）。FOLFOXIRI组转移灶的R0二次切除率更高（在所有244例患者中为6%对15%；P=.033；仅在肝转移患者中为12%对36%；P=.017）。FOLFOXIRI组的无进展生存期（PFS）和总生存期（OS）均显著改善（中位PFS，6.9对9.8个月；风险比[HR]，0.63；P=.0006；中位OS，16.7对22.6个月；HR，0.70；P=.032）。