改良FOLFOXIRI方案一线治疗晚期结直肠癌的疗效及生存预后分析

Efficacy and survival analysis of modified FOLFOXIRI as the first-line chemotherapy in metastatic colorectal cancer

目的:观察改良FOLFOXIRI方案一线治疗晚期结直肠癌的近期疗效、远期生存及不良反应。方法:采用前瞻性观察研究方法对47例晚期结直肠癌患者采用m FOLFOXIRI方案一线化疗。伊立替康(IRI)165mg/m2静脉滴注90min d1,奥沙利铂(OXA)85mg/m2静脉滴注2h d1,亚叶酸钙400mg/m2静脉滴注2h d1,5-FU 2 400~2 800mg/m2持续静脉滴注48h,每2周为一周期。观察该方案的近期疗效及不良反应,并通过长期随访进行生存分析。结果:47例晚期结直肠癌患者治疗的总有效率(ORR)为51.1%,疾病控制率(DCR)为85.1%,中位无进展生存期(PFS)8.4个月(95%CI:6.6~10.2个月),中位总生存期(OS)20.7个月(95%CI:15.3~26.1个月)。根据年龄及ECOG PS评分将患者分为体力状况较好组及体力状况中等组,两组近期疗效及PFS、OS均无显著统计学差异。亚组分析显示肿瘤早期缓解患者较非早期缓解患者的PFS及OS延长且具有统计学意义(PFS:11.0个月vs 7.1个月,P=0.044;OS:29.7个月vs 20.7个月,P=0.036);原发灶位于左半结肠/直肠者较右半结肠者的PFS及OS延长且具有统计学意义(PFS:10.6个月vs3.7个月,P=0.002;OS:27.3个月vs 14.2个月,P=0.021)。全组不良反应较轻,以I-II级为主,III-IV级不良反应主要为中性粒细胞减少及延迟性腹泻,但均为可控,无治疗相关死亡。结论:改良FOLFOXIRI三药联合方案作为晚期结直肠癌的一线治疗方案,其有效率高、不良反应可耐受,并可达到较长的生存时间,原发灶部位及是否达到早期缓解与患者预后生存可能有关,值得进一步临床研究。

Objective：To investigate the therapeutic effect,long- term survival and side effects of m FOLFOXIRI for patients with metastatic colorectal cancer（ m CRC）. Methods：Prospective observational study included 47 patients with metastatic colorectal cancer treated with the m FOLFOXIRI regimen from January 2008 to October 2012. The FOLFOXIRI regimen：Irinotecan 165 mg / m2d1,Oxaliplatin 85mg/m2d1,5- FU 2 400 ~ 2 800mg/m2 continuous infusion for 48 hours,Leucovorin 400 mg / m2d1,all repeated every 2 weeks. The short- term efficacy and side effects were investigated. And survival analysis was performed using Kaplan- Meier method by long- term follow- up. Results：For 47 patients,the objective response rate was 51. 1%,and the disease control rate was 85. 1%. The median progression- free survival（ PFS） was 8. 4 months（ 95% CI：6. 6 ~ 10. 2） and median overall survival（ OS） was 20. 7 months（ 95% CI：15. 3 ~ 26. 1）,respectively. There was no significant difference in short- term efficacy,OS,or PFS between the good PS group and the median PS group. In the subgroup analysis,the median PFS and OS of EOTR（ early objective tumor response） group were significantly longer than non- EOTR group（ PFS：11. 0 vs 7. 1 months,P = 0. 044;OS：29. 7 vs 20. 7 months,P = 0. 036）. The median PFS and OS of left colon or rectum were significantly longer than that of right colon（ PFS：10. 6 vs 3. 7 months,P = 0. 002; OS：27. 3 vs 14. 2 months,P = 0. 021）. The most common grade III / IV adverse events were neutropenia（ 34. 0%） and diarrhea（ 14. 9%）. No therapy associated death occurred. Conclusion：m FOLFOXIRI as the first- line chemotherapy of m CRC can get great short- term efficacy and prolong the survival time with good tolerance. The location of primary tumor and early objective tumor response may be associated with improved survival time. And the triplet chemotherapy regimen merits further investigation in future clinical studies.