Concomitant Or Adjuvant Temozolomide With Whole Brain Irradiation For Brain Metastases: A Meta-analysis

Background Brain metastases (BMs) are the most common form of intracranial tumors in adults, Even though surgery and radiosurgery can produce effective palliation in selected cases, whole brain irradiation (WBI) is considered standard treatment for the patients with multiple BMs. Temozolomide (TMZ) is an oral alkylating agent, the highly bio-availabity, crossing the BBB and achieving effective concentrations in the CNS are considered as the most superiority of it. We conducted a meta-analysis to assess the effect of combined TMZ with WBI in patients with BMs.Methods PubMed (1966 to Mar 2008), EMBASE(1974 to Mar 2009), Cochrane Library(Issue 1,2009), Chinese Biomedical Literature Database (1978 to Mar 2009), China Journal Fulltext Database (1994 to Mar 2009), and Chinese Scientific Journals Fulltext Database (1989 to Mar 2009) were searched to identify relevant original published trails in any date, and the references of eligible studies were manually screened. We also retrieved relative meeting trials. Randomized Controlled Trails were reported in English or Chinese; comparing concomitant or adjuvant temozolomide plus whole brain irradiation (TMZ+WBI) with whole brain irradiation alone (WBI) in patients with brain metastases from any primary tumor, were eligible for inclusion. Two investigators independently assessed the quality of included trials and extracted data. The RevMan 5 software was used for statistical analysis.Results Four trials (include 2 English,1 Chinese and 1 Meeting Abstract) involving 280 patients were included. The studies'quality was poor because of the method of randomization, allocation concealment, and blinding all unclear. The baseline of trials were comparable include age, performance status, primary site, and treatment modality. The result showed that group TMZ+WBI was superior to group WBI in partial response, stable disease, progressive disease, and objective response with the pooled RR value and 95% CI respectively 1.89 (1.19,3.02),0.82(0.45,1.50),0.29 (0.10,0.78), and 1.72 (1.32,2.24). The incidence of gastrointestinal symptoms and≥Grade 3 myelosuppression presented statistical difference, TMZ+WBI group is higher than WBI group, the pooled RR value and 95% CI were 3.75 (1.04,13.44) and 13 (1.75,96.79), respectively.4 trials all reported TMZ+WBI group is longer than WBI group in median survival (4.5month versus 3.1 month,8.6month versus 7.0month,8.6 month versus 4.5 month, and 7.9 month versus 4.3 month). Conclusions The present available evidence showed that the combination of TMZ and WBI may moderately improve the response rate, but accordingly increase the incidence of gastrointestinal symptoms and myelosuppression. Future large-scale, high-quality, placebo-controlled, double-blind trials are needed.