FOLFIRINOX 或吉西他滨作为胰腺癌的辅助治疗。

FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer.

机构信息

From the Institut de Cancérologie de Lorraine and Université de Lorraine (T.C.) and Centre Hospitalier Universitaire (L.C.), Nancy, Hôpital Beaujon and University Paris VII, Clichy (P.H., A.S.), Hôpital Huriez, Lille (M.H.), Centre Paul Strauss, Strasbourg (M.B.A.), Institut Paoli-Calmettes, Marseille (J.-L.R.), Centre Antoine-Lacassagne, Nice (E.F.), Hôpital Jean-Mermoz, Lyon (P.A.), Hôpital Trousseau, Tours (T.L.), Centre Hospitalier Universitaire de Saint-Eloi (E.A.) and Institut du Cancer de Montpellier-Val d'Aurelle, Université de Montpellier (M.Y., S.G., F.C.), Montpellier, Centre Hospitalier Départemental Vendée, La Roche-sur-Yon (R.F.), Centre Hospitalier Universitaire Robert Debré, Reims (J.V.), Hôpital Louis Pasteur, Colmar (G.B.), Normandie University, Rouen University Hospital, Rouen (F.D.F.), Hôpital Layné, Mont-de-Marsan (P.T.), Centre Hospitalier Universitaire Côte de Nacre, Caen (K.B.-L.), Hôpital Saint-Jean, Perpignan (F.K.-A.), Centre Hospitalier Régional, Orléans (J.-L.L.), R&D Unicancer (B.J., C.J.-Z.) and Sorbonne Université, Hôpitaux Universitaires Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris (J.-B.B.), Paris, Gustave Roussy, Université Paris-Saclay, Villejuif (D.M.), and Centre Hospitalier Universitaire, Dijon (P.R.) - all in France; and the Princess Margaret Cancer Centre, Toronto (A.C.W.), Kingston General Hospital (J.J.B.) and the Canadian Cancer Trials Group, Queen's University (C.J.O.), Kingston, ON, the Ottawa Health Research Institute, Ottawa (C.C.), and Segal Cancer Centre, Jewish General Hospital, Montreal (P.K.) - all in Canada.

出版信息

N Engl J Med. 2018 Dec 20;379(25):2395-2406. doi: 10.1056/NEJMoa1809775.

DOI:10.1056/NEJMoa1809775

PMID:30575490

Abstract

BACKGROUND

Among patients with metastatic pancreatic cancer, combination chemotherapy with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) leads to longer overall survival than gemcitabine therapy. We compared the efficacy and safety of a modified FOLFIRINOX regimen with gemcitabine as adjuvant therapy in patients with resected pancreatic cancer.

METHODS

We randomly assigned 493 patients with resected pancreatic ductal adenocarcinoma to receive a modified FOLFIRINOX regimen (oxaliplatin [85 mg per square meter of body-surface area], irinotecan [180 mg per square meter, reduced to 150 mg per square meter after a protocol-specified safety analysis], leucovorin [400 mg per square meter], and fluorouracil [2400 mg per square meter] every 2 weeks) or gemcitabine (1000 mg per square meter on days 1, 8, and 15 every 4 weeks) for 24 weeks. The primary end point was disease-free survival. Secondary end points included overall survival and safety.

RESULTS

At a median follow-up of 33.6 months, the median disease-free survival was 21.6 months in the modified-FOLFIRINOX group and 12.8 months in the gemcitabine group (stratified hazard ratio for cancer-related event, second cancer, or death, 0.58; 95% confidence interval [CI], 0.46 to 0.73; P<0.001). The disease-free survival rate at 3 years was 39.7% in the modified-FOLFIRINOX group and 21.4% in the gemcitabine group. The median overall survival was 54.4 months in the modified-FOLFIRINOX group and 35.0 months in the gemcitabine group (stratified hazard ratio for death, 0.64; 95% CI, 0.48 to 0.86; P=0.003). The overall survival rate at 3 years was 63.4% in the modified-FOLFIRINOX group and 48.6% in the gemcitabine group. Adverse events of grade 3 or 4 occurred in 75.9% of the patients in the modified-FOLFIRINOX group and in 52.9% of those in the gemcitabine group. One patient in the gemcitabine group died from toxic effects (interstitial pneumonitis).

CONCLUSIONS

Adjuvant therapy with a modified FOLFIRINOX regimen led to significantly longer survival than gemcitabine among patients with resected pancreatic cancer, at the expense of a higher incidence of toxic effects. (Funded by R&D Unicancer and others; ClinicalTrials.gov number, NCT01526135 ; EudraCT number, 2011-002026-52 .).

摘要

背景

在转移性胰腺癌患者中，氟尿嘧啶、亚叶酸、伊立替康和奥沙利铂联合化疗（FOLFIRINOX）的总生存期长于吉西他滨治疗。我们比较了改良 FOLFIRINOX 方案联合吉西他滨作为可切除胰腺癌辅助治疗的疗效和安全性。

方法

我们随机分配 493 例接受可切除胰腺导管腺癌治疗的患者，接受改良 FOLFIRINOX 方案（奥沙利铂[85mg/平方米体表面积]、伊立替康[180mg/平方米，根据方案规定的安全性分析后降至 150mg/平方米]、亚叶酸[400mg/平方米]和氟尿嘧啶[2400mg/平方米]每 2 周一次）或吉西他滨（1000mg/平方米，每 4 周一次，第 1、8 和 15 天）治疗 24 周。主要终点是无病生存期。次要终点包括总生存期和安全性。

结果

中位随访 33.6 个月时，改良 FOLFIRINOX 组的中位无病生存期为 21.6 个月，吉西他滨组为 12.8 个月（分层癌症相关事件、第二癌症或死亡风险比，0.58；95%置信区间[CI]，0.46 至 0.73；P<0.001）。改良 FOLFIRINOX 组 3 年无病生存率为 39.7%，吉西他滨组为 21.4%。改良 FOLFIRINOX 组中位总生存期为 54.4 个月，吉西他滨组为 35.0 个月（分层死亡风险比，0.64；95%CI，0.48 至 0.86；P=0.003）。改良 FOLFIRINOX 组 3 年总生存率为 63.4%，吉西他滨组为 48.6%。改良 FOLFIRINOX 组 75.9%的患者发生 3 级或 4 级不良事件，吉西他滨组为 52.9%。吉西他滨组 1 例患者死于毒副作用（间质性肺炎）。