A System Review Of Concomitant Or Adjuvant Temozolomide With Whole Brain Radiotherapy For Patients With Brain Metastasis From Non-small Cell Lung Cancer

Purpose:To evaluate the effectiveness and safety of concomitant or adjuvant TMZ with WBRT in the management of non-small cell lung cancer patients with brain metastases. Methods:All of the randomized controlled trials comparing whole brain radiotherapy plus temozolomide with whole brain radiotherapy alone were searched from the following databases:PubMed (1966 to Mar 2015), EMBASE(1974 to Mar 2015), Cochrane Library (Issue 1,2015), Chinese Biomedical Literature Database (1978 to Mar 2015), and China Journal Fulltext Database (1994 to Mar 2015). Website, related journals, conference papers and other possible sources were manually retrieved. Search result was screened according to the inclusive and exclusive criteria. The date extraction and quality assessment of eligible RCTs were conducted by two reviewers independently according to Cochrane reviewer’s handbook 5.1.0 and the Cochrane collaboration’s tool for assessing risk of bias. The RevMan 5.3 software was used for meta-analysis. Results:Six eligible RCTs involving 427 patients were included. Two of the trials indicated the method of random sequence generation, and one study was an open label, multicentric RCTs, all other trials did not mention the method of randomization, allocation concealment and blinding. Meta-analysis showed that TMZ plus WBRT made a potential benefit for patients with brain metastasis from NSCLC. Specifically in objective response rate, the TMZ+WBRT group was superior to WBRT group (62.6% vs 46.0%), and the difference between two groups was significant with a P value of 0.0004, the RR and 95%CI were 1.41 (1.17,1.71). Regretfully, the combined therapeutic model did not make any difference in over survival and progress-free survival, the P value, HR and 95%CI were 0.60,1.09 (0.80,1.48) and 0.59,1.15(0.73,1.80), respectively. The incidence of III/ Ⅳ grade hematological toxicity of the TMZ+ WBRT group is much higher than the WBRT group, P value was 0.02, RR and 95%CI were 2.14(1.12,4.06). The gastrointestinal symptoms in the TMZ+WBRT group were also higher than in the WBRT group, but there was no statistical difference between two groups, with a P value of 0.06, and the RR and 95%CI were 1.84(0.98,3.47). Three trials reported symptom of headache, and the incidence was observed frequently in the combined group than in the control group. However, the difference between two groups with no significant statistical meaning, P value was 0.66, RR and 95%CI were 1.13(0.67,1.89). Conclusion:Existing evidence suggested that the combined therapeutic model of TMZ plus WBRT improved the objective response rate, but no survival benefit achieved for the patients with brain metastasis from NSCLC. Meanwhile, the Ⅲ/Ⅳ grade hematological toxicity and gastrointestinal symptom rate were increased. The side effects are mild to moderate, patients usually be recovered without special medical intervention, thus it can be thought that the safety and patients’tolerance of the combined therapeutic model of TMZ plus WBRT are well. In view of the defect, such as small scale and low quality of the included studies, this conclusion need to be further proved with more high-quality, large-scale, and double-blind RCTs.