重组人血管内皮抑素联合化疗治疗骨肉瘤的前瞻性对照非随机临床研究

A Prospective Non-randomized Controlled Clinical Trial on Endostar Combined with Chemotherapy for Treatment of Patient with Osteosarcoma

目的:探讨重组人血管内皮抑素(恩度)联合新辅助化疗治疗II期经典型骨肉瘤的疗效。方法:2013年1月至2014年7月我院骨肿瘤科治疗72例II期经典型骨肉瘤患者,根据病人意愿将病人分为新辅助化疗联合恩度组和单纯化疗组。单纯化疗组化疗方案为:阿霉素30 mg/m2静滴,d1-d3,顺铂120 mg/m2静滴,d4;甲氨蝶呤10-12 g/m2静滴,d1;异环磷酰胺3 g/m2静滴,d1-d5。新辅助化疗联合恩度组在化疗基础上加用恩度,初期8个病例恩度15 mg/d,d1-d5,配合化疗每周期4次,术前术后各一个周期,总剂量40支;后期14个病例,恩度15 mg/d,d1-d10,配合化疗每周期4次,术前术后各一个周期,总剂量80支。化疗后根据化疗结果进行手术治疗,术后对手术标本进行组织学评估和免疫组化染色,测量化疗前后联合组和对照组肿瘤坏死率、血管内皮生长因子(vascular endothelial growth factor,VEGF)及微血管密度(microvessel density,MVD)。结果:72例患者入组,剔除资料不全5例,共纳入评价67例,其中联合组22例,对照组45例。术后进行随访,随访时间3-19个月,平均随访时间11.5个月。两组在肿瘤坏死率无明显差异,但术前术后比较,VEGF染色和MVD联合组较对照组有明显下降。结论:本研究显示恩度联合新辅助化疗并不能提高肿瘤坏死率,但恩度能有效抑制肿瘤新生血管生成。

Objective： To investigate the efficacy of rh-endostatin（endostar） combined with chemotherapy agiainst stage II osteosarcoma. Methods： Patients of stage II osteosarcoma treated in Shanghai No.6 People’s Hospital Department of bone tumor from January 2013 to July 2014 were divided into Endostar combined chemotherapy group and control group. The regimen of chemotherapy was as follows, doxorubicin 30 mg/m2 iv drop d1-d3, cisplatin 120 mg/m2 iv drop d4, methotrexate 10-12 g/m2 iv drop d1, ifosfamide 3g/m2 iv drop d1-d5. Endostar was added in the combined group based on the same chemotherapy（15 mg iv drop d1-d5 at the beginning of 8 cases, 4 times was a cycle, each cycle was used before and after the operation, 600 mg in total; later 14 cases, 15 mg iv drop d1-d10,4 times was a cycle, each cycle was used before and after the operation, 1200 mg in total）. After operation, specimens were performed histological evaluation and immunohistochemistry, and then tumor cell necrosis rate（TCNR）, vascular endothelial growth factor（VEGF）and microvessel density（MVD） were measured. Results： A total of 72 patients were enrolled in the study, and 5 cases were excluded in the final analyse because of the incomplete data. In the 67 patients could be evaluated, 22 cases were in combined group and 45 cases were in control group. Patients were followed up 3-19 months with the average period of 11.5 months. After the operation we had the histological evaluation and the immunohistochemical staining. The two groups had no significant difference in the tumor necrosis rate,while compared before and after operation, the VEGF and MVD of the combined group were significantly lower than those of the control group. Conclusion： Endostar combined with chemotherapy can not increase the TCNR, but endostar can inhibit tumor angiogenesis effectively.