论文部分内容阅读
背景与目的 :替莫唑胺(temozolomide,TMZ)国内外多推荐为胶质瘤的一线化疗药物,化疗周期通常为六周期。长周期(超过六周期)TMZ治疗胶质瘤国外已有多篇文献报道,但中国脑胶质瘤患者这方面信息较少。本文总结我们近年来长周期TMZ治疗32例胶质瘤的临床经验,重点探讨其安全性。方法:32例高级别胶质瘤(high-grade gliomas,HGGs)或低级别胶质瘤(low-grade gliomas,LGGs)采用了TMZ长周期治疗。TMZ化疗方案的选择基于肿瘤组织DNA甲基转移酶(O6-methylguanine-DNA methyltransferase,MGMT)的免疫组化检测结果,用甲基化特异PCR(MSP-PCR)检测了其中6例的MGMT启动子甲基化程度。MGMT阴性表达(±或-)者接受TMZ标准化疗(200mg/(m2.d),d1-5,四周方案),MGMT阳性表达(+或++)者接受TMZ剂量密度方案[75mg/(m2.d),d1-21,4周方案],或顺铂(cisplatin,DDP)联合TMZ化疗方案[DDP 75mg/(m2.d),d1-2;TMZ 200mg/(m2.d),d2-6,四周方案]。结果:32例患者共接受318周期TMZ方案化疗。患者化疗周期数为7~24(中位周期数为9.4)。最常见的严重毒性反应是Ⅲ度淋巴细胞减少症与白细胞减少症,发生率均为9.4%(3/32)。最常见的轻至中度毒性反应依次为疲乏(86.9%)、中性粒细胞减少症(46.9%)、脱发(46.9%)、血小板减少症(40.6%)、便秘(41.2%)及淋巴细胞减少症(25.0%)等。中位无进展生存(progress free survival,PFS)为28.6月。6月PFS、12月PFS分别为100%与71%。32例患者中,15例肿瘤完全切除,至今无病生存。依据意向性治疗原则(intention-to-treatprinciple,ITT),1例(3.1%)取得完全缓解(complete response,CR),14例(43.8%)微效(minor response,MR),2例(6.2%)稳定(stable disease,SD)。总反应率(overall response rate,ORR)为81.5%(95%CI,50%~96%),疾病控制率(disease control rate,DCR)为89.2%(95%CI,64%~98%)。结论:长周期TMZ化疗治疗胶质瘤是安全的。长周期TMZ化疗具有较高的反应率(ORR)与无进展生存(PFS)。
BACKGROUND & OBJECTIVE: Temozolomide (TMZ) is a first-line chemotherapy drug recommended mostly in glioma at home and abroad. The chemotherapy cycle is usually six cycles. Long cycle (more than six cycles) TMZ treatment of glioma has been reported in many foreign literature, but Chinese glioma patients in this area less information. This article summarizes our recent experience of long-term TMZ treatment of 32 cases of glioma clinical experience, focusing on its safety. Methods: Thirty-two patients with high-grade gliomas (HGGs) or low-grade gliomas (LGGs) were treated with TMZ long-term therapy. TMZ chemotherapy regimen was selected based on the results of immunohistochemistry of tumor tissue DNA methyltransferase (MGMT). Six MGMT promoters were detected by MSP-PCR Degree of methylation. Patients with MGMT negative (+ or -) received TMZ standard chemotherapy (200 mg / (m2.d), d1-5, four week regimen) and MGMT positive (+ or ++) .d), d1-21, 4weeks regimen], or cisplatin (DDP) combined with TMZ regimen [DDP 75mg / (m2.d), d1-2; TMZ 200mg / (m2.d) 6, four weeks program]. Results: Thirty-two patients received 318 cycles of TMZ regimen. The number of chemotherapy cycles for patients was 7 to 24 (the median number of cycles was 9.4). The most common serious toxic reactions are grade III lymphopenia and leukopenia, the incidence was 9.4% (3/32). The most common mild to moderate toxicities were fatigue (86.9%), neutropenia (46.9%), alopecia (46.9%), thrombocytopenia (40.6%), constipation (41.2%) and lymphocytes Reduce disease (25.0%) and so on. The median progression-free survival (PFS) was 28.6 months. June PFS, December PFS were 100% and 71%. Of the 32 patients, 15 had a complete resection of the tumor and have survived so far. According to the intention-to-treat principle (ITT), complete response (CR) was obtained in 1 patient (3.1%), minor response (MR) in 14 patients %) Stable disease (SD). The overall response rate (ORR) was 81.5% (95% CI, 50% -96%) and the disease control rate (DCR) was 89.2% (95% CI, 64% -98%). Conclusion: Long-term TMZ chemotherapy for glioma is safe. Long-term TMZ chemotherapy has a high response rate (ORR) and progression-free survival (PFS).