Systematic review and meta-analysis of preoperative chemoradiotherapy with or without oxaliplatin in locally advanced rectal cancer

BACKGROUND Preoperative chemoradiotherapy has become the current standard regimen for locally advanced rectal cancer (LARC). However, the additional benefit of oxaliplatin to preoperative chemotherapy was still controversial. On one hand, oxaliplatin may improve the tumor response rate of even prolong the survival time. On the other hand, it can bring a series of adverse effects. Opinions vary from studies to studies. We aim to perform a meta-analysis to evaluate the efficacy, safety, and long-term survival of oxaliplatin in preoperative chemoradiotherapy for LARC. METHOD To identify clinical trials fusing oxaliplatin in preoperative chemoradiotherapy for LARC published until December 2015, we searched PubMed, the Cochrane Library, and the Springer Link databases by combining various key words. We also search for relevant ASCO conferences. Data were extracted from every study to perform a meta-analysis using STATA 12.0 software. RESULT Eleven articles or ASCO abstracts from 8 studies with a total of 5597 patients were included. Adding oxaliplatin to preoperative chemoradiotherapy can significantly improve the ypCR rate [risk ratio (RR) = 1.208, 95% confidence interval (95% CI): 1.070-1.364, P = 0.002, I = 14.5%], and decrease the preoperative metastasis (RR = 0.494, 95% CI: 0.256-0.954, P = 0.036, I = 53.9%) and local recurrence rate (RR = 0.761, 95% CI: 0.616-0.941, P = 0.012, I = 26.1%). What's more, oxaliplatin can prolong the disease-free survival (DFS) [hazard ratio (HR) = 0.867, 95% CI: 0.741-0.992, P = 0.000, I = 16.3%]. However, oxaliplatin can increase the chemoradiotherapy-related toxicities (RR = 1.858, 95% CI 1.427-2.419, P = 0.000, I = 84.7%). There was no significant difference between the groups with and without oxaliplatin in operation rate, R0 resection rate, sphincter preservation rate, permanent stoma rate, postoperative complication, mortality, and overall survival. CONCLUSION Preoperative chemoradiotherapy with oxaliplatin bring both advantage and disadvantage to LARC. Whether to use oxaliplatin should be decided by patient's general condition and tolerance. Although oxaliplatin can prolong the DFS, survival benefit should be proved by further data.