转移性结直肠癌的 FOLFOXIRI 和贝伐珠单抗初始治疗。

Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer.

机构信息

From Azienda Ospedaliero-Universitaria Pisana and Università di Pisa, Pisa (F.L., C. Cremolini, G.M., L.S., A.F.), Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua (S.L., V.Z.), Sapienza Università di Roma (E.C.) and Università Campus Biomedico (G. Tonini), Rome, Azienda Istituti Ospitalieri, Cremona (G. Tomasello), Ospedale San Raffaele, IRCCS, Milan (M.R.), Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Turin (R.S.), Fondazione Poliambulanza, Brescia (A.Z.), Centro di Riferimento Oncologico, IRCCS, Aviano (A.B.), Ospedale Versilia, Lido di Camaiore (D.A.), Ospedale San Martino, IRCCS, Genoa (S.C.), Azienda Ospedaliera Universitaria Federico II, Naples (C. Carlomagno), Arcispedale Santa Maria Nuova, IRCCS, Reggio Emilia (C.B.), Ospedale Felice Lotti, Pontedera (G.A.), and Azienda Ospedaliero-Universitaria Careggi and Istituto Toscano Tumori, Florence (L.B.) - all in Italy.

出版信息

N Engl J Med. 2014 Oct 23;371(17):1609-18. doi: 10.1056/NEJMoa1403108.

DOI:10.1056/NEJMoa1403108

PMID:25337750

Abstract

BACKGROUND

A fluoropyrimidine plus irinotecan or oxaliplatin, combined with bevacizumab (a monoclonal antibody against vascular endothelial growth factor), is standard first-line treatment for metastatic colorectal cancer. Before the introduction of bevacizumab, chemotherapy with fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) showed superior efficacy as compared with fluorouracil, leucovorin, and irinotecan (FOLFIRI). In a phase 2 study, FOLFOXIRI plus bevacizumab showed promising activity and an acceptable rate of adverse effects.

METHODS

We randomly assigned 508 patients with untreated metastatic colorectal cancer to receive either FOLFIRI plus bevacizumab (control group) or FOLFOXIRI plus bevacizumab (experimental group). Up to 12 cycles of treatment were administered, followed by fluorouracil plus bevacizumab until disease progression. The primary end point was progression-free survival.

RESULTS

The median progression-free survival was 12.1 months in the experimental group, as compared with 9.7 months in the control group (hazard ratio for progression, 0.75; 95% confidence interval [CI], 0.62 to 0.90; P=0.003). The objective response rate was 65% in the experimental group and 53% in the control group (P=0.006). Overall survival was longer, but not significantly so, in the experimental group (31.0 vs. 25.8 months; hazard ratio for death, 0.79; 95% CI, 0.63 to 1.00; P=0.054). The incidences of grade 3 or 4 neurotoxicity, stomatitis, diarrhea, and neutropenia were significantly higher in the experimental group.

CONCLUSIONS

FOLFOXIRI plus bevacizumab, as compared with FOLFIRI plus bevacizumab, improved the outcome in patients with metastatic colorectal cancer and increased the incidence of some adverse events. (Funded by the Gruppo Oncologico Nord Ovest and others; ClinicalTrials.gov number, NCT00719797.).

摘要

背景

氟嘧啶类药物联合伊立替康或奥沙利铂，联合贝伐单抗（一种抗血管内皮生长因子的单克隆抗体），是转移性结直肠癌的标准一线治疗方法。在贝伐单抗问世之前，氟尿嘧啶、亚叶酸钙、奥沙利铂和伊立替康（FOLFOXIRI）化疗方案与氟尿嘧啶、亚叶酸钙和伊立替康（FOLFIRI）相比，疗效更优。在一项 2 期研究中，FOLFOXIRI 联合贝伐单抗显示出有前景的疗效和可接受的不良反应发生率。

方法

我们将 508 例未经治疗的转移性结直肠癌患者随机分为接受 FOLFIRI 联合贝伐单抗（对照组）或 FOLFOXIRI 联合贝伐单抗（实验组）治疗。给予最多 12 个周期的治疗，然后给予氟尿嘧啶联合贝伐单抗，直至疾病进展。主要终点是无进展生存期。

结果

实验组的中位无进展生存期为 12.1 个月，而对照组为 9.7 个月（进展风险比为 0.75；95%置信区间[CI]，0.62 至 0.90；P=0.003）。实验组的客观缓解率为 65%，对照组为 53%（P=0.006）。实验组的总生存期较长，但无统计学意义（31.0 与 25.8 个月；死亡风险比为 0.79；95%CI，0.63 至 1.00；P=0.054）。实验组的 3 级或 4 级神经毒性、口腔炎、腹泻和中性粒细胞减少症发生率明显较高。