课件：恶性脑肿瘤的化疗方案课件.ppt

ASCO 2009,Abstract 2037 2009年ASCO有关神经系统肿瘤的文献80余篇 A phase II study of XL184 in patients (pts) with progressive glioblastomamultiforme (GBM) in first or second relapse. Conclusions: XL184at a dose of 175 mg PO qd, has demonstrated substantial activity in ptswith progressive or recurrent GBM. ASCO 2009, Abstract 2047 26Pts. PR SD PD 6-PFS(ms) 38% 35% 27% (9pts received bevacizumab) 脑胶质瘤和转移性瘤耐药的研究 1) 6-甲基鸟嘌呤DNA甲基转移酶 (MGMT) (6-methylguanine-DNA hyltransferase ) 2) P-glycoprotein Fruehauf, J. P. et al. Clin Cancer Res 2006;12:4523-4532 脑胶质瘤和转移性瘤耐药的研究 Fruehauf, J. P. et al. Clin Cancer Res 2006;12:4523-4532 MGMT methylation status as a prognostic factor in anaplastic astrocytomas. Conclusions: MGMT methylation status is an independent prognostic factor together with age in AA. Pts.71/80(88.8%) 30/71(M) 41/71(UM) MGMT methylation M-PFS(ms) 48.6 38 p=0.09 ASCO 2009 Abstract 2052 P-gp expression in brain capillary endothelial cells suggests that P-gp may restrict drug entry into brain tumors and thus be another mechanism of drug resistance. K1735 cells K1735 cells MDR The biology and mechanism of chemoresistance of brain metastases THE UNIVERSITY OF TEXAS GRAD. SCH. OF BIOMED. SCI. AT HOUSTON 1995 BBBD(blood-brain barrier disruption)化疗 高渗性、缓激肽衍生物：BBB开放 选择性开放血瘤屏障(blood-tumor barrier, BTB) 克服化疗耐药性 多药耐药及逆转 MGMT表达预测化疗疗效，避免无效化疗。 脑胶质瘤和转移性瘤耐药的研究 联合化疗提高化疗敏感性 VM-26和BCNU联合显著提高胶质瘤对化疗的敏感性 ※机理：抑制MDR-I或P-gp过表达 PCV方案显著增强多形胶质母细胞瘤对BCNU类药制的敏感性 ※机理：肿瘤细胞先暴露于烷化剂类药物使瘤 细胞中AGT（O6-烷基鸟嘌呤-DNA烷基化转酶） 　　　活性受抑　　　　 AGT是增强肿瘤细胞对BCNU类 药物敏感性的主要靶点 Randomized Comparison of Intra-arterial Versus Intravenous Infusion of ACNU for Newly Diagnosed Patients with Glioblastoma To compare the effectiveness of intra-arterial ACNUwith intravenous ACNU in newly diagnosed patients with supratentorial glioblastoma. ACNU (80mg/m2) once every 6 weeks concomitant with radiotherapy. 病人数 可评价病人数 MS(w) PFS(w) Toxici