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To determine the maximum tolerated dose (MTD) of continuous oral capecitabine plus oxaliplatin and pre-operative pelvic radiotherapy (XELOX-RT).Patients with clinically unresectable rectal cancer or for whom resection with histologically clear (R0) surgical margins was unlikely received continuous capecitabine (500–825 mg/m2 twice daily, 7 days/week), oxaliplatin 2-h intravenous infusion (130 mg/m2 days 1 and 29) and pelvic radiotherapy (Monday–Friday for 5 weeks, total dose 45 Gy in 25 daily 1.8 Gy fractions). The MTD was the capecitabine dose causing dose-limiting toxicities (DLTs; treatment-related grade 3/4 toxicities) in one-third or more of patients treated per dose level.Eighteen patients received three dose levels. The MTD was capecitabine 825 mg/m2 twice daily: DLTs occurred in two of six patients (grade 3 diarrhoea, rectal pain with local skin reaction). No DLTs occurred in six patients receiving capecitabine 650 mg/m2 twice daily. Grade 3/4 toxicity was rare, with minimal myelosuppression. Although predominantly a dose-finding study, XELOX-RT showed promising activity. Fourteen patients had histologically confirmed R0 resections and five had a pathological complete response.The recommended dose for further study is capecitabine 650 mg/m2 twice daily with oxaliplatin and radiotherapy. XELOX-RT showed promising antitumour activity. Further evaluation is underway.