重组人血管内皮抑素联合FOLFOX方案二线治疗晚期结直肠癌临床研究

Clinical study of endostar combined with FOLFOX as a second line chemotherapy for advanced colorectal cancer

目的前瞻性观察重组人血管内皮抑素（商品名：恩度）联合FOLFOX方案二线治疗晚期大肠癌的有效性和安全性。方法23例患者均为经细胞学或病理确诊，既往已用奥沙利铂（L—OHP）或伊立替康或卡培他滨等药治疗后肿瘤复发进展的晚期结直肠癌，重组人血管内皮抑素15mg＋0．9％氯化钠溶液500ml静脉滴注4h，第1天至第14天，L-OHP85mg／m^2静脉滴注2～3h，第1、15天，亚叶酸钙（cF）200mg静脉滴注2h后，5-氟尿嘧啶（5-Fu）400mg／m^2静脉推注，随后5-Fu600mg／m^2静脉持续滴注22h，第1天至第2天、第15天至第16天，每4周为1个周期，至少化疗2个周期后行疗效评价。按照RECIST标准严格观察和评价近期客观疗效，根据NCICTC（3．0）评价药物毒性反应。结果23例患者共完成56个周期化疗，均可评价疗效和不良反应，获得PR8例，SD12例，PD3例，近期客观有效率为34．8％（8／23），控制率87．0％（20／23），中位疾病进展时间（MTTP）为7个月，1年生存率50．0％（8／16），2年生存率40．0％（2／5）。Ⅲ-Ⅳ度毒性主要与化疗药物有关，其中，白细胞下降5例（21．7％），血红蛋白下降1例（4．3％），血小板下降3例（13．0％）。2例既往有高血压病患者出现血压轻度增高，3例发生暂时性心电图改变，表现为ST段轻度改变，不影响治疗，无治疗相关性死亡。结论重组人血管内皮抑素联合FOLFOX方案二线治疗晚期大肠癌疗效好，毒性低，安全性和耐受性均较好，值得临床进一步研究。

Objective To observe prospectively and systematically the effect and safety of rhendostati injection （endostar） combined with FOLFOX as a second line chemotherapy for advanced/metastatic colorectal cancer. Methods 23 patients with histological confirmed advanced/metastatic colorectal cancer after first line chemotherapy failure were observed. The dosage of 15 mg/time of endostar solved in 500ml normal saline was slowly intravenously dropped 4 h from day 1 to day 14. Oxaliplatin 85 mg/m^2 iv 2-3 h dl, d15. CF 200 mg/m^2 iv 2 h followed by 5-Fu 400 mg iv bolus and 5-Fu 600 mg/m^2 iv 22 h dl-2, d15-16 were given, every 4 weeks as one cycle. Efficacy was evaluated after 2 cycles according to RECIST criteria. Results 23 cases had been completed totally 56 cycles. Among 23 cases, 8 cases were PR, 12 cases SD, and 3 cases PD. The objective response rate （RR） was 34.8 % （8/23）, and the disease control rate （DCR） was 87.0 % （20/23）. The median time to progression was 7 months. The 1-year survival rate were 50.0 %. The 2- year survival rate was 40.0 %. The occurrence rate of G3/4 toxicities was low, including neutropenia（21.7 %）, anemia（4.3 %）, thrombocytopenia （13.0 %）. Those toxicities were mainly related with the chemotherapy agents. Meanwhile transient electrocardiogram changes mild ST-T of changes occurred in 3 cases. 2 cases were mild hypertension and were symptomatically controlled. Conclusion There are better efficacies of endostar combined with FOLFOX chemotherapy for advanced/metastatic coloreetal cancer, and it is low toxic arid tolerable. It is worth of further clinical observation. More experiences need to be accumulated.