Adjuvant capecitabine in advanced nasopharyngeal carcinoma following concurrent chemoradiotherapy: A meta-analysis and systematic review.
Authors: Velasco Rogelio Nona , Ladrera Guia Elena Imenda Rodrigu , Imasa Marcelo Severino Bulauitan , King Rich Ericson Chan , Tan Harold Nathan , Kanesvaran Ravindran 
Published: June 2023

e18067 Background: Nasopharyngeal cancer (NPCA)is commonly diagnosed at an advanced stage with a high propensity for distant metastasis to the bone, liver, and lungs. Despite current treatment options, prognosis remains dismal for locally advanced disease with 5-year overall survival (OS) rates between 53 to 80% and 28 to 61% in stages III and IV, respectively. Locally advanced NPCA is commonly treated with induction or adjuvant chemotherapy and concurrent chemoradiotherapy. The survival benefit of cisplatin with 5-flurouracil used after concurrent chemoradiotherapy remains controversial. Some patients are also unable to tolerate the side effects of the chemotherapy doublet after local treatment. Thus, other options which may confer survival advantage are needed. Capecitabine has been investigated in two randomized controlled trials as an adjuvant treatment option after concurrent chemoradiotherapy in locally advanced NPCA with conflicting survival results. This systematic review and meta-analysis sought to examine the effect of adjuvant capecitabine after concurrent chemoradiotherapy in locally advanced NPCA compared with observation on survival outcomes. Methods: A comprehensive systematic search was conducted to examine the effect of adjuvant capecitabine after concurrent chemoradiotherapy in locally advanced NPCA. Systematic search was done using MEDLINE, CENTRAL, Clinicaltrials.gov, and Google Scholar for randomized controlled trials published from inception February 1, 2023. Data on failure-free survival (FFS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), overall survival (OS), and adverse events were extracted. Hazard ratios (HR) or relative risks (RR) with 95% confidence intervals (95% CI) were pooled from the included studies and summarized using RevMan 5.3. Results: Two randomized controlled trials (n = 586) with low risk of bias were included in the analysis. The use of adjuvant capecitabine improved FFS (HR 0.51; 95% CI 0.36, 0.73), LRFS (HR 0.42; 95% CI 0.23, 0.74), DMFS (HR 0.58; 95% CI 0.38, 0.89), and OS (HR 0.51, 95% CI 0.31, 0.86). There were more grade 3 to 4 hand-foot syndrome on the capecitabine arm (RR 21.93; 95% CI 2.97, 161.89). There was no significant difference on the incidence of any grade 3 to 4 adverse events, and grades 3 to 4 leukopenia, neutropenia, nausea, and fatigue. There was no significant interstudy heterogeneity observed for all outcomes except for the occurrence of any grade 3 to 4 adverse events (I2 89%). Conclusions: The pooled results show a survival advantage on the use of adjuvant capecitabine after concurrent chemoradiotherapy for locally advanced nasopharyngeal carcinoma with a tolerable safety profile. Capecitabine may be considered as an adjuvant treatment option for NPCA patients especially those unable to tolerate platinum-based therapy.