The Long-term Efficacy Of Temozolomide In Patients With Glioblastoma

ObjectiveA clinical study was performed to determine the efficacy of temozolomide vs carmustine in patients with glioblastoma and examine the effect of O6-methylguanine DNA-methyltransferase expressiom on the prognosis of glioblastoma.MethodsTwo hundred and eighty-three patients with pathologically confirmed glioblastoma were treated with chemotherapy from January2004to January2009in neurosurgery department of Huanhu Hospital. All the patients were randomly, volunteered, single-blindly divided into temozolomide group(TMZ group) and carmustine group (BCNU group). The glioma tissues were examined for MGMT protein expression by immunohistochemistry(The tumor tissue biopsy were observed under the microscope. We define the coloring particles in the nucleus or cytoplasm>10%as positive and the opposite is negative). The TMZ group receive radiotherapy plus continuous daily temozolomide (fractionated focal irradiation in daily fractions of1.8-2Gy given5days per week for6weeks, for a total of54-60Gy;75mg per square meter of body-surface area per day,7days per week from the first to the last day of radiotherapy), followed by six cycles of adjuvant temozolomide (150to200mg per square meter for5days during each28-day cycle) or receive adjuvant temozolomide alone (150to200mg per square meter for5days during each28-day cycle). The BCNU group receive80mg per square meter for3days during each6-week cycle. All the patients were followed up in the long term for the survival time、tumor respense and drug safety.Results1, The TMZ group’s cumulative survival rate are higher than BCNU group:the median survival time of TMZ group is19.2±0.6month, the two-year survival rate is31%(30\97), the five-year survival rate is6.2%(6\97); while the median survival time of BCNU group is15.6±0.6month, the two-year survival rate is14%(26\186), the five-year survival rate is0.5%(1\186). The two groups had significant effect.2, In TMZ group, the patients of complete respond is2, partial respond is23, stable disease is48, progressive disease is24, the objective response rate was75.26%. In BCNU group, the patients of complete respond is0, partial respond is16, stable disease is68. progressive disease is102, the objective response rate was45.16%. The two groups had significant effect.3,In all of the patients, MGMT-positive group’s median survival time was16.8±0.5months, while MGMT-negative group’s median survival time was17.2±0.8months. It don’t have significant difference between the two groups. In the BCNU group, MGMT-positive group’s median survival time was14.9±0.8months, while MGMT-negative group’s median survival time was16.4±0.6months. It don’t have significant difference between the two groups. In the TMZ group, MGMT-positive group’s median survival time was19.1±0.6months, while MGMT-negative group’s median survival time was19.6±2.4months. It don’t have significant difference between the two groups.4,The two groups have varying degrees of nausea, vomiting, loss of appetite and other gastrointestinal symptoms. The patients’symptom in the TMZ group is lesser, only18cases of patients required antiemetic therapy. The patients’symptom in the BCNU group is more serious and most of the patients need antiemetic therapy. But there are still22cases of patients need intravenous nutrition support therapy because of intractable vomiting.29cases in the TMZ group result in grade1or2hematologic toxic effects, but they can return to normal after drug reduction.8cases in the TMZ group result in grade3or4hematologic toxic effects, but they can return to normal after drug reduction and symptomatic treatment.140cases in the BCNU group result in grade1or2hematologic toxic effects,38cases result in grade3or4hematologic toxic effects.It need to give medication. The two groups had significant effect.ConclusionTMZ showed more efficient object respond rate and higher cumulative survival rate compared with BCNU and had nothing to do with MGMT. It had less adverse reaction and better tolerability. Therefore, it is an ideal drug of postoperative adjuvant chemotherapy for Glioblastoma.