Oxaliplatin-containing regimens have been safely and successfully used in combination with concurrent radiation in treatment of solid tumors such as rectal and esophageal cancers. The Lyon R0-04 phase II trial utilized the combination of Oxaliplatin, infusional 5FU and radiation in the treatment of rectal cancer. A total of 40 operable subjects were entered onto the study. Radiotherapy was delivered with A three-field technique to a dose of 50 Gy (total dose) over 5 weeks with a concomitant boost approach. Two cycles of chemotherapy were given synchronously on weeks 1 and 5, with Oxaliplatin 130 mg/m2 in day 1 followed by continuous infusion of fluorouracil 350 mg/mg2 and L-folinic acid 100mg/m2 for 5 days. Surgery was planned 5 weeks later. All subjects completed treatment without modification except one who experience grade 3-4 toxicity. Grade 3 toxicity was seen in seven subjects. Surgery was performed in all subjects after a mean interval time of 5 weeks. An objective clinical response was seen in 30 subjects (75%). Sphincter-saving surgery was possible in 26 subjects. No postoperative deaths occurred. In four subjects (10%), a reoperation was necessary (anastomotic fistula, n=2; pelvic abscess, n=2). In six cases the operative specimen was sterilized (15%), and in 12 cases (30%), only few residual cells were detected. Such a combined preoperative chemoradiotherapy and Oxaliplatin-containing regimen is well tolerated with no increase surgical toxicity. The good response rate observed warrants its use in further clinical trials.