替莫唑胺治疗颅内恶性胶质瘤疗效观察

Study on therapeutic effect of temozolomide in malignant intracranial glioma

目的观察替莫唑胺治疗颅内恶性胶质瘤疗效。方法选择2002-2003年收治的50例经病理证实的恶性胶质瘤患者,其中间变性星形细胞瘤26例,胶质母细胞瘤24例。男32例,女18例;年龄19～67岁,平均年龄42.5岁。随机分为2组,每组各25例患者,替莫唑胺组(试验组)中胶质母细胞瘤12例、间变性星形细胞瘤13例,平均病程为4个月;环己亚硝脲组(对照组)胶质母细胞瘤12例、间变性星形细胞瘤13例,平均病程3.5个月。按照身高及体质量确定体表面积,分别接受下述治疗方案。(1)试验组:按150mg/m2体表面积计算,25例患者于试验第1～5天口服替莫唑胺胶囊。第1天需同时口服环己亚硝脲安慰剂,剂量为130mg/m2。(2)对照组:第1天口服环己亚硝脲,剂量为130mg/m2,第1～5天口服替莫唑胺安慰剂150mg/m2。2组均每疗程服药5d,28d为1个治疗周期,连续治疗3个周期。3个周期后1个月,开始进行疗效观察,并长期随访观察患者的生存期长度。结果(1)生存时间:替莫唑胺组患者平均生存期较环己亚硝脲组明显延长,差异具有显著性意义(P<0.001)。(2)生存质量:经随访,替莫唑胺组患者生活质量提高并保持稳定。(3)药物安全性:替莫唑胺组2例出现白细胞数减少,5例发生恶心、呕吐,均出现于每周期服药第1天,无明显肝、肾功能异常。环己亚硝脲组10例白细胞数减少、血小板?

Objective To study the therapeutic effect of temozolomide in malignant intracranial glioma. Methods Fifty in-patients, during 2002-2003, with pathological identified glioma including anaplastic astrocytoma (n=26) and glioblastoma (n=24) were enrolled. These patients aged 19-67 years (average 42.5 years), 32 male and 18 female were randomly divided into two groups (25 patients for each group). In temozolomide group (experiment group) glioblastoma 12 cases and astrocytoma 13 cases with average course of 4 months were included, and in lomustine group (control group), glioblastoma (n=12) and astrocytoma (n=13) with average course of 3.5 months were included. The therapeutic scheme was formulated according to the patients' body surface area (BSA) calculated from body weight and height. In experiment group temozolomide capsule (150 mg/m2 BSA) was given orally in 1 st-5 th day and simulated lomustine capsule (placebo) 130 mg/m2 BSA was given while in the 1 st day. In control group lomustine capsule was administrated orally (130 mg/m2 BSA) at the 1 st day and the simulated temozolomide (placebo) 150 mg/m2 BSA was given in the 1 st-5 th day. In both groups drugs were given in the first 5 days of 28 day therapeutic course. The treatment study was completed in three consecutive therapeutic courses, then the therapeutic effects were evaluated in 1 month after the 3 rd course. The patients were followed up in long term for observation the survival time. Results The average survival time of patients in temozolomide group were longer than that in lomustine group with significant difference (P < 0.001). After following up, the quality of life of patients in temozolomide group were improved and keeping stable. The adverse effects of temozolomide were found as leukopenia (in 2 cases), nausea and vomit (n=5) at the 1 st day in treatment but abnormal liver function and renal function were not found. In lomustine group the adverse effects were leukopenia (n=10), thrombocyteopenia (n=10), secondary aplastic anemia (n=1), obvious nausea and vomit (n=15). Conclusion It demonstrates that there is significant therapeutic effect of temozolomide in malignant glioma with mild adverse effects only.