Activity And Safety Of Bevacizumab Plus Temozolomide For Recurrent Malignant Gliomas

Background and objective Recurrent malignant glioma is the most common and devastating primary malignant intracranial tumor in adults, it has the characteristics of Progress quickly and high mortality. In the case of glioblastoma, the current first-line treatment is surgical resection followed by radiotherapy plus concomitant and adjuvant temozolomide. This treatment may prolong the survival period of the patient, but the overall effect is not ideal. Almost all patients will relapse again after first-line treatment, because it proliferates fast and is difficult to be removed completely. After recurrence, its malignant degree is higher, the prognosis is extremely poor. Dose-intense temozolomide can cause persistent DNA damage through the full amount and intensive drug delivery, then make the DNA damage repair enzyme MGMT deplete continuously, reduce the activity of MGMT, and change the drug resistance of temozolomide caused by the high expression of MGMT, thus improve the curative effect of chemotherapy effectively. China central nervous system disease diagnosis and treatment guidelines recommend: radiation and temozolomide treatment failure for the patients with recurrent high-grade glioma can choose for dose-intense temozolomide. Recurrent malignant glioma is a type of highly vascularized tumor with increased expression levels of vascular endothelial growth factor(VEGF), Bevacizumab(BEV) is a recombinant humanized monoclonal antibody tha tcan combine VEGF specificly, block its biological effect, reduce tumor angiogenesis, inhibite tumor growth finally. BEV is approved by the NCCN as a monotherapy treatment or combination with cytotoxic drug for patients with recurrent glioma. But there is no generally accepted drug combination, and for bevacizumab whether it can improve the long-term survival of patients is still controversial. Based on the effectivenesss of dose-intense temozolomide, this study observed 49 cases of recurrent malignant glioma to investigate the activity and safety of bevacizumab plus temozolomide combination in the treatment of recurrent malignant gliomas.Method A total of 49 recurrent malignant gliomas patients from April 2012 to May 2014 in the first affiliated hospital of Zhengzhou university were admitted in this study, patients were confirmed as malignant glioma by pathological histology. They were randomly divided into two groups: experimental group 25 cases to receive bevacizumab plus temozolomide treatment, control group 24 cases shall be received temozolomide treatment only. Bevacizumab was infused by intravenous drip every two weeks, the dose is 10mg/m2. For the Temozolomide used dose density plan:Temozolomide was taken orally from 1 to 7 and 15 to 22 days(Every other week for medicine/drug withdrawal, the dose is 150mg/m2, 28 days is one course. Review head MRI scan + enhancements every 4 weeks to evaluate the efficacy of the treatment. Then analyze the response rate, median progression-free survival, median overall survival and occurrence of adverse reactions of two groups. We used SPSS 20.0 statistic software to process and analysis data, the progression free and overall survival rates were calculated by the Kaplan-Meier method. The log-rank test was used to analysis the significance of differences in survival. The difference of attribute data between the two groups compared with chi-square test, the P value<0.05 was considered statistically significant.Result 1.25 patients of experimental group completed a total of 258 times of bevacizumab theray and each patient completed at least 2 cycles.One patient(4%) had complete remission, eleven patients(44%) had partial response, nine patients(36%) had stable diseases, and four patients(16%) had progressive diseases. The response rate was 48%,The disease control rate was 84%. 24 patients of control group received 79 cycles of temozolomide treatment. Five patients(20.8%) had partial response, eight patients(33.3%) had stable diseases, and eleven patients(45.8%) had progressive diseases. The response rate was 20.8%, the disease control rate was 54.2%, the difference of RR and DCR between two groups have statistical significance(P < 0.05). 2. Until May 2015, the median PFS of experimental group were 6 months(95% C.I:4.784-7.216), the 6-month PFS rate determined as 44%, median OS was 9.5 months(95% C.I:7.705-11.295). The median PFS of control group were 4 months(95% C.I:2.672-5.328), the 6-month PFS rate determined as 29.2%, median OS was 7.4 months(95% C.I:5.008-9.792). The differences of PFS and OS between two groups have statistical significance(P < 0.05). 3. Major toxicities were gastrointestinal reaction and myelosuppression. Among which, most were I-II adverse reactions. High blood pressure and the nasal bleeding were bevacizumab ralated adverse reactions, but the incidence of adverse reactions between the two groups have no statistical difference(P > 0.05).Conclusion Bevacizumab plus temozolomide showed good short-term and long-term curative effect in the treatment for recurrent malignant gliomas, compared with the singal drug of temozolomide. At the same time, it has high safety in the treatment for which can be used as a preferred option in recurrence malignant glioma chemotherapy.