肺癌脑转移瘤病例分享.pptVIP

替莫唑胺通过 DNA 甲基化发挥细胞毒作用 DNA甲基化是替莫唑胺产生细胞毒作用的主要机制： 甲基化重氮阳离子是一种活性甲基化化合物，能够将甲基转移到DNA上，引起DNA蓄积性损伤，并最终经细胞凋亡导致细胞死亡。 替莫唑胺作用机制示意图 有效透过血脑屏障，迅速进入脑脊液，直达肿瘤病灶 该研究也提示：肿瘤病灶内浓度显著高于正常脑组织内浓度 RT+TMZ组（n=25）, 放疗剂量相同，同步口服替莫唑胺75mg/m2/天至放疗结束，后续替莫唑胺200mg/m2/天x5，Q28DX6CS 脑转移患者，患者随机接受全脑放疗(RT)或 全脑放疗+替莫唑胺治疗(RT+TMZ) （n=48） 中位随访时间为4个月 主要研究终点为治疗有效率和 神经学症状改善情况 研究设计 RT组（n=23） 40Gy/20次 放疗， 2Gy/F By D. Antonadou. J Clin Oncol 20:3644-3650 病例资料 By D. Antonadou. J Clin Oncol 20:3644-3650 替莫唑胺同步放化疗+辅助化疗有效率显著优于单独放疗组 By D. Antonadou. J Clin Oncol 20:3644-3650 替莫唑胺同步放化疗+后续化疗 vs. 单独放疗组：CR: 38% vs. 33% ; PR: 58% vs. 33% P=0.017 替莫唑胺同步放化疗+辅助化疗组神经学功能改善明显 D. Antonadou, J Clin Oncol. 2002 Sep 1;20(17):3644-50 在TMZ+RT组，level I and II:治疗前为80%，化疗后升高到92% ；level III 的病人从治疗前的20%，化疗后降低为8% ； 在RT组，level I and II，治疗前为74% ，化疗后升高到81%， level III 的病人从治疗前的26% ，化疗后降低为19%。 神经学功能改善明显，2个月后需要糖皮质激素治疗的患者比例（67% vs 91 %，P0.05） Neurologic function scale Level Ⅰ fully functional Level Ⅱ fully functional not able to work Level Ⅲ stays in bed and needs help half the time Level Ⅳ requires help all the time By D. Antonadou. J Clin Oncol 20:3644-3650 * * * * The functional status of the patient was assessed by two examiners and was also self-assessed by the patient. A baseline functional assessment before the start of treatment demonstrated that neurologic functional status was well balanced between treatment groups and that the majority of patients had level I and II functional status (Table 1). In the TMZ RT group, the proportion of patients with level I and II status increased from 80% before treatment to 92% after RT, whereas the proportion of patients with level III status decreased from 20% to 8% (Table 3). In comparison, in the RT group, the proportion of patients with level I and II status increased from 74% to 81%, whereas the proportion of patients with level III status decreased from 26% to 19%. * * * * 主要研究终点为放射效应和神经学症状，中位生存期为7月 vs8.6月(P=NS)，总有效率为67% vs96%（P=0.017），未报到疾病进展时间，复发时间，也未报到患者的死因。接受替莫唑胺治疗的患者神经学症状改善更好，更少患者接受类固醇治疗 替莫唑胺