贝伐珠单抗联合FOLFIRI方案一线治疗转移性结直肠癌的临床研究

Study of bevacizumab combined with FOLFIRI as first-line treatment for patients with metastatic colorectal cancer

目的评价贝伐珠单抗联合FOLFIRI方案一线治疗转移性结直肠癌的疗效和安全性。方法将42例转移性结直肠癌患者随机分为FOLFIRI组和FOLFIRI+贝伐珠单抗组。FOLFIRI组(n=21)采用伊立替康(CPT-11,180 mg/m^2,d1)+甲酰四氢叶酸钙(CF,400 mg/m^2,d1)+氟尿嘧啶(5-FU,400 mg/m^2,静脉推注,d1;然后5-FU,2400 mg/m^2,以微量泵进行持续静脉滴注46小时)。FOLFIRI+贝伐珠单抗组(n=21)采用贝伐珠单抗(每2周5 mg/kg,d1)+FOLFIRI方案。2周为1个周期,3个周期后评价疗效。两组患者均持续治疗至病情进展或毒性不能耐受。结果 42例患者均可评价疗效和不良反应。FOLFIRI组和FOLFIRI+贝伐珠单抗组的治疗有效率分别为28.6%和61.9%,FOLFIRI+贝伐珠单抗组的有效率显著高于FOLFIRI组(P=0.03)。FOLFIRI+贝伐珠单抗组的临床获益率明显高于FOLFIRI组(90.5%vs 61.9%,P=0.03)。FOLFIRI组和FOLFIRI+贝伐珠单抗组中位无疾病进展时间(progression-free survival,PFS)分别为6.6个月和10.0个月(P=0.000)。两组的主要不良反应为迟发性腹泻和中性粒细胞减少,贝伐珠单抗组增加的不良反应主要有高血压(P=0.002)、出血(P=0.001)和蛋白尿(P=0.035)。结论 FOLFIRI方案化疗联用贝伐珠单抗提高了晚期结直肠癌患者治疗的有效率和临床获益率,并延长了PFS,不良反应患者可以耐受。

Objective To assess the efficacy and safety of bevacizumab plus FOLFIRI as the first line treatment in metastatic colorectal cancer （mCRC） patients. Method 42 previously untreated mCRC patients were randomized to FOL- FIRI group （n = 21 ） and FOLFIRI ＋ bevacizumab group （n = 21 ）. The FOLFIRI group was administered with CPT-11 180 mg/m2 dl, CF 400 mg/m2 dl ＋ 5-FU 400 mg/m2 bolus iv. ,dl, then 5-FU 2400 mg/m2 dl was given intravenously by continuous micro-pump infusion for 46 hours. FOLFIRI ＋ bevacizumab group was given bevacizumab 5 mg/kg （ every 2 weeks, dl ） and FOLFIRI. Two weeks constitutes one cycle, and the efficacy and safety were evaluated after 3 cycles. The treatment continued until disease progression or unacceptable toxicity occurred. Result All patients were evaluable for re- sponse, survival and toxicity analysis. In the FOLFIRI ＋ bevacizumab group, the response rate （61.9%） and clinical bene- fit response rate （ 90. 5% ） were significantly higher than those of the FOLFIRI group respectively （P 〈0. 05）. The median progression-free survival （PFS） of FOLFIRI ＋ bevacizumab group was 10. 0 months, which was significantly improved as compared with 6. 6 months in the FOLFIRI group （P =0. 000）. The common toxicity profiles of FOLFIRI and FOLFIRI ＋ bevacizumab regimens were delayed diarrhea and neutropenia, while the toxicities related to bevacizumab were consistent with that documented in previous literature, which were hypertension （P--O. 002 ）, hemorrhage （P = 0. 001 ） and proteinuria （ P = O. 035 ）. Conclusion The addition of bevacizumab to FOLFIRI regimen significantly improves the response rate, clini- cal benefit response rate and PFS in first line treatment for patients with mCRC and its toxicity is well tolerated.