化疗联合重组人血管内皮抑素治疗ⅡB期骨肉瘤的前瞻性同期对照非随机临床研究

A controlled non-randomized clinical research on chemotherapy combined with rh-endostatin for stage ⅡB ostosarcoma

目的探讨化疗联合重组人血管内皮抑素(恩度)治疗ⅡB期骨肉瘤的远期疗效及安全性。方法收集2008年1月至2012年4月北京积水潭医院骨肿瘤科住院治疗的ⅡB期骨肉瘤患者,分为恩度联合化疗组和单纯化疗对照组。化疗方案如下:甲氨蝶呤10g/m2静滴,d1;异环磷酰胺3g/m2静滴,d1～d5;顺铂120mg/m2静滴,d1;阿霉素30mg/m2静滴,d1～d3。联合组在化疗的基础上加用恩度(15mg静滴,d1～d14,21天为1周期,共4个周期)。结果 388例患者入组,剔除和研究终止有58例,共纳入评价330例,其中联合组58例,对照组272例。随访6～59个月,中位随访时间为20.2个月。对照组1、2、3年无远处转移生存率分别为79%、70%和65%,联合组分别为93%、86%和77%(P=0.045)。对照组1、2、3年无进展生存率分别为76%、66%和60%,联合组分别为90%、83%和74%(P=0.025)。对照组1、2、3年生存率分别为94%、84%和79%,联合组分别为98%、94%和85%(P=0.220)。两组的不良反应以1～2级为主,3～4级不良反应主要为白细胞减少,贫血、恶心呕吐和肝功能损害,两组不良反应差异无统计学意义。结论恩度联合化疗治疗骨肉瘤能显著提高无远处转移生存率和无疾病进展生存率,不良反应可耐受,值得临床深入研究。

Objective To investigate the efficacy and safety of chemotherapy combined with rh-endostatin （endostar） against stage ⅡB ostosarcoma. Methods Patients of stage Ⅱ B ostosarcoma enrolled in Beijing Jishuitan Hospital from January 2008 to April 2012 were divided into combined group and control group. The regimen of chemotherapy was as follows： methotrexate 10g/m2 iv d1 , if- osfamide 3g/m2 iv d1-d5, cisplatin 120mg/m2 iv d1, doxorubicin 30mg/m2 iv d1-d3. Based on the same chemotherapy, endostar was added in combined group （ 15rag iv d1-d14, 21days was a cycle, for 4 cycles）. Results A total of 388 patients were enrolled in this study, and 58 cases were excluded in the final analysis. In the 330 patients could be evaluated, 272 cases were in control group and 58 in combined group. Patients were followed up 6-59 months with a median period of 20. 2 months. In the control group, 1-, 2- and 3- year distant metastasis-free survival rates were 79% , 70% and 65% respectively, while those of combined group were 93% , 86% and 77% with statistical difference （P = 0. 045 ）. In control group, 1-, 2- and 3-years of progression-free survival rates were 76% , 66% and 60% , respectively, while those of combined group were 90% , 83% and 74% with statistical difference （P = 0. 025 ）. In the con- trol group, 1-, 2- and 3-year overall survival rates were 94% , 84% and 79% , while those of combined group were 98%, 94% and 85 % without statistical difference （P = 0. 220）. The side effects in the two groups were mainly in grade 1-2, and the common grade 3- 4 side effects were leucopenia, anemia, hepatic dysfunction, nausea and vomiting. There was no difference in side effects of the two groups. Conclusion The combination of chemotherapy and endostar can significantly improve the distant metastasis-free survival and progression-free survival in osteosarcoma patients, with tolerable side effects, worthy further study.