Randomized phase III trial in elderly patients comparing LV5FU2 with or without irinotecan for first-line treatment of metastatic colorectal cancer (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)
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DOI：
10.1093/annonc/mdv491
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发表时间：
2016-01-01
影响因子：
50.5
通讯作者：
Mitry, E.
中科院分区：
文献类型：
--
作者：
Aparicio, T.;Lavau-Denes, S.;Mitry, E.
转移性结直肠癌（mCRC）常发生在老年患者中。然而，缺乏关于老年患者对伊立替康双联化疗（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，既往未经治疗的mCRC老年患者（75岁以上）按照2 x 2析因设计（4组）随机分配接受基于5-FU（5-氟尿嘧啶）的CT治疗，单独（FU：LV5 FU 2或简化LV5 FU 2）或联合伊立替康[IRI：LV5 FU 2-伊立替康或简化LV5 FU 2-伊立替康（FOLFIRI）]。CLASSIC组定义为LV5 FU 2或LV5 FU 2-伊立替康，SIMPLIFIED组定义为简化LV5 FU 2或FOLFIRI。主要终点是无进展生存期（PFS）。从2003年6月至2010年5月，71例患者被随机分配到LV5 FU 2组，71例患者被随机分配到简化LV5 FU 2组，70例患者被随机分配到LV5 FU 2-伊立替康组，70例患者被随机分配到FOLFIRI组。中位年龄为80岁（范围75-92岁）。未观察到中位PFS的显著差异：FU 5.2个月vs IRI 7.3个月，风险比（HR）= 0.84（0.66-1.07），P = 0.15; CLASSIC 6.5个月vs SIMPLIFIED 6.0个月，HR = 0.85（0.67-1.09），P = 0.19。IRI（P = 0.0003）的ORR上级IRI（FU 21.1% vs 41.7%）和CLASSIC（P = 0.04）：CLASSIC 37.1% vs SIMPLIFIED 25.6%。FU组的中位OS为14.2个月，IRI组为13.3个月，HR = 0.96（0.75-1.24）; CLASSIC组为15.2个月，SIMPLIFIED组为11.4个月，HR = 0.71（0.55-0.92）。IRI中出现3-4级毒性的患者更多（52.2% vs 76.3%）。在该老年人群中，在基于5-FU的输注CT中添加伊立替康并未显著增加PFS或OS。与简化LV5 FU 2相比，经典LV5 FU 2与OS改善相关。NCT 00303771。
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.Elderly patients (75+) with previously untreated mCRC were randomly assigned in a 2 x 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).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%).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.NCT00303771.