伊立替康联合替吉奥二线及三线治疗晚期结直肠癌的临床观察

Irinotecan combined with S-1 in second and third line treatment of advanced colorectal cancer

目的观察伊立替康联合替吉奥(IRIS)方案二线及三线治疗晚期结直肠癌(colorectal cancer,CRC)的近期疗效和安全性。方法一线及二线方案治疗失败的晚期CRC患者接受IRIS方案治疗:伊立替康180 mg/m2,d1,联合替吉奥2周或3周重复;替吉奥:体表面积(body surface area,BSA)<1.25 m2时40 mg,BSA≥1.25 m2、≤1.50 m2时50 mg,BSA>1.50 m2时60 mg,每天2次口服,d1-7,2周重复,或d1-14,3周重复;2周方案治疗每4周期评价疗效,3周方案每2周期评价疗效;治疗每周期评价不良反应。结果共51例可评价患者,治疗后疗效达完全缓解0例(0%)、部分缓解22例(43.1%)、稳定17例(33.3%)、进展12例(23.5%),临床获益率76.5%。中位无进展生存时间(progress free survival,PFS)5.0(95%CI:3.7-6.3)月。单因素Cox回归模型分析显示,二线、三线IRIS方案治疗后疗效对PFS有影响(HR:1.91,95%CI:1.27-2.87,P=0.002);多因素Cox回归模型分析显示,肿瘤低分化的患者较中分化患者PFS有延长(HR:0.14,95%CI:0.05-0.43,P=0.001),治疗疗效对PFS有影响(HR:2.80,95%CI:1.63-4.83,P=0.000),PS评分为0分的患者较1分者PFS有延长趋势(HR:2.93,95%CI:0.98-8.76,P=0.054)。≥3度不良反应为粒细胞减少及消化道反应。结论 IRIS方案二线及三线治疗晚期CRC临床获益率高,总体安全性较好。

Objective To evaluate the short-term efficacy and safety of irinotecan combined with S-1 （IRIS） regimen in the second and third line treatment of advanced colorectal cancer （CRC）. Methods Fifty-one evaluable patients with advanced CRC,who failed in the first or second line therapy,were enrolled and treated with the IRIS regimen. The IRIS regimen consisted of irinotecan 180 mg/m^2 , dl, repeated with S-1,2- or 3-week as a cycle ; S-1 40 mg [ body surface area（BSA） 〈 1.25 m^2 ] ,50 mg（ BSA≥ 1.25 to ≤ 1.50 m^2 ）, or 60 mg（ BSA 〉 1.50 m^2 ） b. i. d, dl-7, repeated every 2- or 3-week as a cycle. Short-term efficacy and side effects were evaluated every 4 cycles of 2-week treatment and every 2 cycles of 3-week treatment. Results In 51 evaluable patients there were none with complete response （CR）, 22 patients with partial response（PR,43. 1% ）, 17 with stable disease（SD,33. 3% ）, and 12 with progressive disease（ PD, 23.5% ） after IRIS treatment with a clinical benefit rate of 76. 5%. The median progression-free survival（PFS） was 5.0 months （95 % CI：3.7-6. 3 ）. Univariate Cox regression showed that disease response after IRIS treatment affected PFS （HR： 1.91,95% CI： 1.27-2. 87, P = 0. 002）. Multivariate Cox regression revealed that patients with poorly differentiated tumor had longer PFS than those with moderately differentiated tumor（ HR：0. 14,95% C]：0. 05-0. 43 ,P = 0. 001 ）, and disease response also affected PFS （ HR ： 2. 80,95 % CI ： 1. 634. 83, P = 0. 000 ）. Patients with performance status （PS） score 0 tended to have better PFS than patients with PS score 1 （HR：2. 93,95% C1：0. 98-8. 76,P = 0. 054）. Main adverse effects were neutropenia and digestive reaction. Conclusion Irinotecan combined with S-1 regimen as second or third line therapy is an effective,well-tolerated and convenient regimen for patients with advanced colorectal cancer.