重组人血管内皮抑制素和沙利度胺联合化疗治疗转移性结直肠癌的临床观察

目的 观察重组人血管内皮抑制素（恩度）、沙利度胺与细胞毒药物联合治疗晚期结直肠癌的疗效和安全性。方法 研究纳入47例2006年1月至2013年1月于中国医学科学院肿瘤医院接受恩度、沙利度胺联合细胞毒药物治疗的转移性结直肠癌患者。分别按照实体瘤的疗效评价标准（RECIST）1.0和国立癌症研究所毒性判定标准（NCI-CTC）4.0评价疗效和毒副反应，同时随访其生存情况。具体给药方案：恩度15 mg/d，加入生理盐水500 ml静脉滴注，d1~d10；沙利度胺150 mg或200 mg，每晚睡前顿服，d1~d10；14 d为1周期。与恩度和沙利度胺联用的化疗方案均为双周方案，包括奥沙利铂+氟尿嘧啶类药物（18例），奥沙利铂+雷替曲塞（1例），伊立替康+氟尿嘧啶类药物（26例）及伊立替康+雷替曲塞（2例）。结果 一线、二线、三线及三线以上接受含恩度+沙利度胺联合化疗方案者的中位生存期依次为26.1（95%CI： 21.9~30.2）、15.3（95%CI：9.5~21.0）和7.5（95%CI：4.2~10.7）个月，中位无进展生存期依次为：11.1（95%CI：8.6~13.7）、7.9（95%CI：4.7~11.2）和4.2（95%CI：1.5~7.0）个月，有效率依次为63.1%、37.5%和16.7%，疾病控制率依次为84.2%、68.7%和66.7%。全组的常见不良反应多为1~2级，包括白细胞减少、中性粒细胞减少、贫血、恶心和呕吐，3、4级毒副反应包括中性粒细胞减少（8.5%）、血小板减少（6.4%）、恶心（4.3%）、呕吐（4.3%）、便秘（4.3%）、疲乏（2.1%）和周围神经毒性（2.1%）。结论 恩度、沙利度胺联合细胞毒药物对初治和复治的转移性结直肠癌患者有较好的疗效及安全性。

Clinical observation of chemotherapy plus combination of rh-endostatin and thalidomide for metastatic colorectal cancer

Objective To evaluate the antitumor activity and toxicity of chemotherapy plus rh-endostatin(endastar) and thalidomide for metastatic colorectal cancer. Methods Forty-seven patients with histologically or pathologically documented metastatic colorectal cancer who underwent endostar and thalidomide-based chemotherapy from January 2006 to January 2013 in our hospital were included in this study. Response to chemotherapy was assessed by RECIST criteria 1.0 and toxicity was evaluated according to National Cancer Institute Common Toxicity Criteria（NCI-CTC） 4.0. The above patients were followed up. Endostar was administered biweekly by intravenous infusion at a dose of 15 mg per day， d1~d10. Thalidomide was administered orally at a dose of 150/200 mg qn， d1~d10. The combined chemotherapy regimens included oxaliplatin and fluoropyrimidine（18 cases）， oxaliplatin and raltitrexed（1 case）， irinotecan and fluoropyrimidine（26 cases） and irinotecan and raltitrexed（2 cases）. Results The median overall survival in first， second and third-line setting were 26.1 months（95%CI： 21.9-30.2）， 15.3 months（95%CI： 9.5-21.0） and 7.5 months（95%CI： 4.2-10.7）， respectively. The median progression-free survival in first， second， and third-line setting were 12.1 months（95%CI： 8.6-13.7）， 7.9 months（95%CI： 4.7-11.2） and 4.2 months（95%CI： 1.5-7.0）， respectively. The overall response rates in first， second and third-line setting were 63.1%， 37.5% and 16.7%， respectively. The disease control rates in first， second and third-line were 84.2%， 68.7% and 66.7%， respectively. The main adverse reaction included leukopenia， neutropenia， anemia， nausea and vomiting， mainly in grade 1-2. The most commonly encountered grade 3 to 4 adverse events included neutropenia（8.5%）， thrombocytopenia（6.4%）， nausea（4.3%）， vomiting（4.3%）， constipation（4.3%）， fatigue（2.1%） and peripheral neuropathy（2.1%）. Conclusion Endostar and thalidomide plus chemotherapy have antitumor activity and are well-tolerated in patients with metastatic colorectal cancer.