UNLABELLED: This was a phase II study of capecitabine in substitution of 5-fluorouracil (5-FU) in the chemoradiotherapy regimen for patients with localized squamous cell carcinoma of the anal canal. BACKGROUND: Combined chemoradiation with infusional 5-FU and mitomycin is the standard treatment for localized squamous cell carcinoma (SCC) of the anal canal. Capecitabine is an oral fluoropirimidine that has been shown to be equally effective to 5-FU in many solid tumors. However, the efficacy of the substitution of 5-FU for capecitabine in anal SCC needs confirmation. METHODS: Patients with SCC of anal cancer T2-4N0M0 or T (any) N1-3M0, with good performance status and normal blood and renal function, were treated with capecitabine 825 mg/m(2) bid during radiotherapy associated with a single dose of mitomycin 15 mg/m(2) on day 1. The primary objective was local control rate at 6 months determined by clinical examination and radiological assessment. Sample size was calculated using the Fleming single-stage design. RESULTS: From November 2010 to February 2014, N = 51 patients were initially included; however, 43 patients were assessed. Seventeen patients (39.5%) were stage II, 11 patients (25.6%) stage IIIA, and 15 patients (34.9%) stage IIIB. Four patients (9.3%) were HIV positive. With a median follow-up of 23.1 months (range 4 to 44.4 months), 3 patients (7%) presented partial response, 37 (86%) had complete response, and 3 patients developed progression of the disease (7%) at 6 months. The colostomy rate was 18.6%. It was observed a locoregional control of 86% in 6 months (CI 95% 0.72-0.94). The main grade 3-4 toxicities were grade 3 radiodermitis in 10 patients (23.2%), grade 3 lymphopenia in 5 patients (11.6%), and grade 3 neutropenia in 2 patients (6.9%). One HIV-positive patient had septic shock, pneumonia, herpetic encephalitis, atrial fibrillation, and macrophage activation syndrome. CONCLUSIONS: Capecitabine can safely substitute infusional 5-FU in the standard chemoradiation regimen for SCC of the anal cancer, with a locoregional control of 86% in 6 months (CI 95% 0.72-0.94).