一项比较 LV5FU2 联合或不联合伊立替康一线治疗转移性结直肠癌的随机 III 期临床试验：老年患者（FFCD 2001-02）。

Randomized phase III trial in elderly patients comparing LV5FU2 with or without irinotecan for first-line treatment of metastatic colorectal cancer (FFCD 2001-02).

机构信息

Department of Gastroenterology, CHU Avicenne, APHP and University Paris 13, Sorbonne Paris Cité, Bobigny

Department of Oncology, CHU Dupuytren, Limoges.

出版信息

Ann Oncol. 2016 Jan;27(1):121-7. doi: 10.1093/annonc/mdv491. Epub 2015 Oct 20.

DOI:10.1093/annonc/mdv491

PMID:26487578

Abstract

BACKGROUND

Metastatic colorectal cancer (mCRC) frequently occurs in elderly patients. However, data from a geriatric tailored randomized trial about tolerance to and the efficacy of doublet chemotherapy (CT) with irinotecan in the elderly are lacking. The benefit of first-line CT intensification remains an issue in elderly patients.

PATIENTS AND METHODS

Elderly patients (75+) with previously untreated mCRC were randomly assigned in a 2 × 2 factorial design (four arms) to receive 5-FU (5-fluorouracil)-based CT, either alone (FU: LV5FU2 or simplified LV5FU2) or in combination with irinotecan [IRI: LV5FU2-irinotecan or simplified LV5FU2-irinotecan (FOLFIRI)]. The CLASSIC arm was defined as LV5FU2 or LV5FU2-irinotecan and the SIMPLIFIED arm as simplified LV5FU2 or FOLFIRI. The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), safety and objective response rate (ORR).

RESULTS

From June 2003 to May 2010, 71 patients were randomly assigned to LV5FU2, 71 to simplified LV5FU2, 70 to LV5FU2-irinotecan and 70 to FOLFIRI. The median age was 80 years (range 75-92 years). No significant difference was observed for the median PFS: FU 5.2 months versus IRI 7.3 months, hazard ratio (HR) = 0.84 (0.66-1.07), P = 0.15 and CLASSIC 6.5 months versus SIMPLIFIED 6.0 months, HR = 0.85 (0.67-1.09), P = 0.19. The ORR was superior in IRI (P = 0.0003): FU 21.1% versus IRI 41.7% and in CLASSIC (P = 0.04): CLASSIC 37.1% versus SIMPLIFIED 25.6%. Median OS was 14.2 months in FU versus 13.3 months in IRI, HR = 0.96 (0.75-1.24) and 15.2 months in CLASSIC versus 11.4 months in SIMPLIFIED, HR = 0.71 (0.55-0.92). More patients presented grade 3-4 toxicities in IRI (52.2% versus 76.3%).

CONCLUSION

In this elderly population, adding irinotecan to an infusional 5-FU-based CT did not significantly increase either PFS or OS. Classic LV5FU2 was associated with an improved OS compared with simplified LV5FU2.

CLINICALTRIALSGOV

NCT00303771.

摘要

背景

转移性结直肠癌（mCRC）常发生于老年患者中。然而，目前缺乏有关老年患者中接受伊立替康联合氟尿嘧啶类药物（5-FU）为基础的双药化疗（CT）的耐受性和疗效的老年患者量身定制的随机试验数据。一线 CT 强化治疗的获益在老年患者中仍是一个问题。

患者和方法

本研究采用 2×2 析因设计（4 个臂），将未经治疗的 mCRC 老年患者（≥75 岁）随机分配至接受 5-FU（氟尿嘧啶）为基础的 CT，单独使用（FU：LV5FU2 或简化 LV5FU2）或联合伊立替康[IRI：LV5FU2-伊立替康或简化 LV5FU2-伊立替康（FOLFIRI）]。CLASSIC 臂定义为 LV5FU2 或 LV5FU2-伊立替康，SIMPLIFIED 臂定义为简化 LV5FU2 或 FOLFIRI。主要终点是无进展生存期（PFS）。次要终点是总生存期（OS）、安全性和客观缓解率（ORR）。

结果

2003 年 6 月至 2010 年 5 月，71 例患者被随机分配至 LV5FU2 组、71 例患者被分配至简化 LV5FU2 组、70 例患者被分配至 LV5FU2-伊立替康组和 70 例患者被分配至 FOLFIRI 组。中位年龄为 80 岁（范围 75-92 岁）。中位 PFS 无显著差异：FU 为 5.2 个月，IRI 为 7.3 个月，风险比（HR）=0.84（0.66-1.07），P=0.15；CLASSIC 为 6.5 个月，SIMPLIFIED 为 6.0 个月，HR=0.85（0.67-1.09），P=0.19。ORR 在 IRI 中更优（P=0.0003）：FU 为 21.1%，IRI 为 41.7%；在 CLASSIC 中更优（P=0.04）：CLASSIC 为 37.1%，SIMPLIFIED 为 25.6%。FU 的中位 OS 为 14.2 个月，IRI 为 13.3 个月，HR=0.96（0.75-1.24）；CLASSIC 的中位 OS 为 15.2 个月，SIMPLIFIED 的中位 OS 为 11.4 个月，HR=0.71（0.55-0.92）。IRI 组更多患者出现 3-4 级毒性（52.2%比 76.3%）。