Prospective phase II trial of neoadjuvant chemo-radiotherapy with Oxaliplatin and Capecitabine in locally advanced rectal cancer (XELOXART)

Neo-adjuvant chemo-radiotherapy (CT–RT) has been shown to decrease local recurrence rate in locally advanced rectal cancer. This multicenter phase II trial was conducted to evaluate the feasibility, safety and effectiveness of a combination of pre-operative radiotherapy and concurrent Capecitabine plus Oxaliplatin (XELOXART Trial). From October 2008 to May 2011, fifty consecutive patients affected with T3/T4 and/or N+ rectal cancer were enrolled. Treatment protocol consisted of 50.4 Gy in 28 fractions, Oxaliplatin 60 mg/m² once a week for 6 weeks and oral Capecitabine 825 mg/m² twice daily from day 1 to 14 and from day 22 to 35. Surgery was planned 6–8 weeks after. Main endpoints were pathological complete response rate (pCR) and the type of surgery performed compared to the planned one at diagnosis. 50 patients were included; pCR (ypT0N0M0) was achieved in 6 patients (12 %). Tumour downstaging was observed in 27 patients (54 %), and nodal downstaging in 32 patients (64 %). A total of 32 patients had lower rectal cancer, with 24 candidate for abdominal-perineal resection. At the end of CT–RT, a total of 12/24 (50 %) underwent conservative surgery. Grade 3 toxicity (fatigue and diarrhoea) occurred in 4 % of patients; grade 4 sensory neuropathy occurred in 2 % of patients. Perioperative complications of any grade occurred in 10 % of patients. Pre-operative CT–RT with Capecitabine-Oxaliplatin was well tolerated and resulted in an encouraging sphincter preservation and tumour downstaging rate. No improvements in terms of pathological complete response rate were shown.