重组人血管内皮抑制素联合替莫唑胺治疗复发高级别胶质瘤的临床研究

目的观察重组人血管内皮抑制素(恩度)联合替莫唑胺(TMZ)与单纯应用TMZ治疗复发高级别胶质瘤患者的安全性与疗效。方法将74例复发高级别胶质瘤患者随机均分为两组,一组单纯应用TMZ化疗(37例),另一组应用恩度联合TMZ联合化疗(37例)。TMZ化疗方案的选择基于患者O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)蛋白表达状况和既往TMZ化疗效果,采用个体化的治疗。恩度剂量为15 mg静脉滴注,连续应用14 d,间歇2周重复。结果 37例单纯TMZ化疗患者共接受129周期化疗,中位3次(1~10次)。完全缓解(CR)1例(2.7%),部分缓解(PR)9例(24.3%),微效(MR)3例(8.1%),疾病控制率(CR+PR+MR)为35.1%。中位无进展生存期(PFS)为4个月(95%CI 1.9~6.1个月),6个月的PFS率为27.0%。37例恩度联合TMZ化疗患者共接受200周期化疗,中位6次(2~10次)。CR 3例(8.1%),PR 14例(37.8%),MR 6例(16.2%),疾病控制率(CR+PR+MR)为62.1%。中位PFS为6个月(95%CI 4.9~7.1个月),6个月的PFS率为43.0%。不良反应中,同单纯TMZ组相比,恩度联合TMZ组具有更高的高血压发生率。结论恩度联合TMZ化疗较TMZ单药化疗在复发高级别胶质瘤的治疗有更好的客观疗效,相对延长PFS,且具有较好的安全性。

Clinical research of recombinant human endostatin combined temozolomide treatment of recurrent high-grade gliomas

Objective To evaluate the safety and efficacy of recombinant human endostatin （Endostar） combined with temozolomide （TMZ） and TMZ alone for recurrent, high-grade gliomas. Methods The 74 cases recurrent high-grade glioma patients were randomly divided into two groups, one guoup of recurrent high-grade gliomas underwent TMZ chemotherapy, another group underwent endostar combined with TMZ chemotherapy. TMZ chemotherapy regimens were selected based on 06-methylguanine- DNA methyl-transferase（MGMT） expression and previous chemotherapy responses. Endostar intravenous dose was 15 mg,1 to 14 days,intermittent two weeks repetition. Results Thirty-seven patients received a total of 129 cycles TMZ chemotherapy,the median 3 times（ 1-10 times）. Complete remission（CR） 1 cases（2. 7% ）, partial remission （PR） was 9 cases （ 24. 3 % ）, minimal remission （MR） was 3 cases （ 8. 1% ）, disease control rate（ CR ＋ PR ＋ MR） was 27%. The median progression-free survival（ progression free survival, PFS） was 4 months（95% CI 1.9-6. 1 months） ,6-month PFS rate was 27.0%. 37 patients received a total of 200 cycles endostar combined with TMZ chemotherapy ,the median 6 times（2-10 times）. 37 patients were evaluable for objective response, complete remission was 3 cases （ 8.1% ）, partial remission was 14 cases （ 37. 8% ）, minimal remission was 6 cases（ 16. 2% ）, disease control rate（ CR ＋ PR ＋ MR）was 62. 1%. The median progression-free survival was 6 months（95% CI 4. 9-7. 1 months） ,6-month PFS rate was 43.0%. Compared with TMZ group,endostar combined with TMZ group had a higher incidence of hypertension. Conclusion Compared with TMZ group, in the treatment of recurrent high-grade gliomas, the group of the endostar combined with TMZ has better objective response, progression-free survival time relative to the extension, and has good security.