Title: Chemotherapy for adults with malignant glioma: a systematic review and network meta-analysis
Abstract: overall survival (OS) and progression-free survival (PFS), but improvements in long-term survival remain challenging.Standard therapy for malignant glioma consists of the maximal tumor resection with concomitant chemoradiotherapy.Among chemotherapy agents, temozolomide (TMZ) is the standard agent used in the treatment of malignant glioma (27).TMZ is an oral alkylating agent that has been shown to improve the survival of patients with malignant glioma.However, even with surgery and TMZ therapy, prognosis remains poor and tumor relapse rates remain high.The relatively modest effects █ InTRODuCTIOn M alignant gliomas are the most common and lethal primary tumors of central nervous system (20), producing serious and progressive disability prior to patient death.Despite the advances in chemoradiotherapy, the survival rate for malignant glioma has remained very low.The majority of glioblastoma patients survive for about two years (17), and only a few patients would survive longer than 5 years (26); WHO III glioma patients would survive ranging from 3 to 5 years ( 22).Surgery and chemoradiotherapy can improve AIM: Malignant glioma is the most common primary brain tumor in adults and the survival rate has remained very low.Thus, determining the optimal treatment for patients can be challenging.To compare the efficacy of common therapies, we performed network meta-analysis to estimate the efficacy and safety among procarbazine, lomustine, vincristine, temozolomide, bevacizumab plus temozolomide, and placebo for patients with malignant glioma. MATERIAL and METhODS:Relevant studies (as of March, 2014) were identified by searching PubMed, Embase, and Central databases.The primary endpoint of the analysis was the overall survival (OS) and progression-free survival (PFS) of glioma patients. RESuLTS:Nine trials with a total of 3472 patients were included in our network meta-analyses.Compared with placebo, bevacizumab plus temozolomide was associated with the highest estimates of OS and PFS for 12 and 24 months (12 month OS odds ratio [OR]: 2.44; 95% credibility interval [CrIs]: 0.76-9.69;24 month OS OR: 2.56; 95% CrIs: 1.12-5.24;12 month PFS OR: 6.76; 95% CrIs: 2.80-17.34;24 month PFS OR: 3.69; 95% CrIs: 0.62-28.63).However, bevacizumab plus temozolomide did not significantly improve OS or PFS compared to temozolomide alone.COnCLuSIOn: Bevacizumab plus temozolomide combination therapy is not significantly more effective than temozolomide alone in improving survival of glioma patients.Moreover, bevacizumab was associated with higher hematologic toxicities.Bevacizumab should be used with caution in glioma patients.Additional randomized controlled trials are required to confirm this finding.