一项在一线治疗初始不可切除或不能完全切除肝转移的结直肠癌患者中三种强化化疗方案的随机 II 期试验。METHEP 试验。

A randomized phase II trial of three intensified chemotherapy regimens in first-line treatment of colorectal cancer patients with initially unresectable or not optimally resectable liver metastases. The METHEP trial.

机构信息

Institut du Cancer de Montpellier-Val d'Aurelle, Montpellier Cedex 05, France,

出版信息

Ann Surg Oncol. 2013 Dec;20(13):4289-97. doi: 10.1245/s10434-013-3217-x. Epub 2013 Aug 17.

DOI:10.1245/s10434-013-3217-x

PMID:23955585

Abstract

PURPOSE

This study was designed to evaluate neoadjuvant intensified chemotherapy in potentially resectable or unresectable liver metastases (LM) from colorectal cancer (CRC).

METHODS

Criteria for potentially resectable LM were complex hepatectomy and/or risky procedure, close contact with major vascular structures, and for unresectable LM, a future liver remnant predicted to be less than 25-30 % of total liver volume. Between October 2004 and August 2007, 125 patients were randomized to either standard (FOLFIRI/FOLFOX4) or intensified chemotherapy (FOLFIRI-HD/FOLFOX7/FOLFIRINOX). Primary endpoint was objective response rate (ORR) after 4 cycles of chemotherapy. Secondary endpoints included safety, R0 surgical resection, best ORR, progression-free survival (PFS), and overall survival (OS).

RESULTS

A total of 122 patients were treated; 45 % of patients had less than 30 % of remaining liver tissue, 20 % had major vascular contact, and 35 % were potentially resectable. Grade 3/4 toxicities were neutropenia (24, 19, 10, 23 %) diarrhoea (0, 6, 3, 23 %), mucositis (0, 3, 0, 7 %), vomiting (7, 9, 0, 3 %), and neurotoxicity (0, 0, 10, 3 %) in arms (FOLFIRI + FOLFOX4)/FOLFIRI-HD/FOLFOX7/FOLFIRINOX, respectively. ORR was 33, 47, 43, and 57 % after the first 4 cycles in arms (FOLFIRI + FOLFOX4)/FOLFIRI-HD/FOLFOX7/FOLFIRINOX, respectively. FOLFIRINOX offered the best conversion rate to resectability (67 %). Disease-free status after chemotherapy and surgery (R0, R1, Rx) was achieved in 54 of 64 operated patients. Median PFS was 9.2 months in control arms versus 11.9 months in experimental arms (hazards ratio [HR] = 0.76, p = 0.115), and the median OS was 17.7 versus 33.4 months (HR = 0.73, p = 0.297), respectively.

CONCLUSIONS

FOLFIRINOX showed promising activity in CRC patients with LM compared with standard or intensified bi-chemotherapy regimens.

摘要

目的

本研究旨在评估新辅助强化化疗对结直肠癌（CRC）潜在可切除或不可切除肝转移（LM）的疗效。

方法

潜在可切除 LM 的标准为复杂肝切除术和/或高风险手术、与大血管结构密切接触，以及不可切除 LM 的标准为预计剩余肝脏体积小于 25-30%。2004 年 10 月至 2007 年 8 月，125 例患者被随机分为标准组（FOLFIRI/FOLFOX4）或强化组（FOLFIRI-HD/FOLFOX7/FOLFIRINOX）。主要终点为 4 个周期化疗后的客观缓解率（ORR）。次要终点包括安全性、R0 手术切除率、最佳 ORR、无进展生存期（PFS）和总生存期（OS）。

结果

共有 122 例患者接受治疗；45%的患者剩余肝脏组织小于 30%，20%的患者存在大血管接触，35%的患者具有潜在可切除性。3/4 级毒性为中性粒细胞减少症（24%、19%、10%、23%）、腹泻（0%、6%、3%、23%）、黏膜炎（0%、3%、0%、7%）、呕吐（7%、9%、0%、3%）和神经毒性（0%、0%、10%、3%），分别见于 FOLFIRI+FOLFOX4、FOLFIRI-HD/FOLFOX7/FOLFIRINOX 组。FOLFIRI+FOLFOX4、FOLFIRI-HD/FOLFOX7/FOLFIRINOX 组患者在第 1 个 4 个周期后的 ORR 分别为 33%、47%、43%和 57%。FOLFIRINOX 组的可切除性转化率最高（67%）。64 例接受手术的患者中，54 例达到化疗和手术的无疾病状态（R0、R1、Rx）。对照组的中位 PFS 为 9.2 个月，实验组为 11.9 个月（风险比[HR]=0.76，p=0.115），中位 OS 分别为 17.7 个月和 33.4 个月（HR=0.73，p=0.297）。