The aim of this study was to evaluate the impact of combined radiotherapy and chemotherapy (leucovorin and 5-fluorouracil) on the treatment of potentially resectable low rectal cancer using the following end points: 1) toxicity of this combined modality regimen; 2) clinical and pathologic response rate and local control; 3) down-staging of the tumor and its influence on the number of sphincter-saving operations; 4) disease-free interval, patterns of relapse, and overall survival.From 1991 to 1996, 118 patients with potentially resectable cases of histologically proven adenocarcinoma and no distant metastases were enrolled into this protocol. All patients were evaluated by clinical and proctologic examination, abdominal computed tomography, transrectal ultrasound, and chest radiography. Therapy consisted of 5,040 cGy (6 weeks) and concurrent leucovorin (20/mg/m2/day) with bolus doses of 5-fluorouracil administered intravenously at 425 mg/m2/day for three consecutive days on the first and last three days of radiation therapy. After two months, all patients underwent repeat evaluation and biopsy of any suspected residual lesions or scar tissue.Median follow-up was 36 months. Toxicity of chemotherapy regimen was minimum. Thirty-six patients (30.5 percent) were classified as being complete responders. In six of these patients, complete response was confirmed by the absence of tumor in the surgical specimens (3 abdominoperineal resections and 3 proctosigmoidectomies with coloanal anastomosis). In the remaining 30 patients, confirmation of a complete response was made by the absence of symptoms, negative findings on physical examination, and biopsy, transrectal ultrasound, and pelvic computed tomographic test results during follow-up. Eighty-two patients (69.4 percent) were considered incomplete responders. Residual lesions had already been identified during the first examination in 74 patients. In the other eight patients, residual tumor was only identified after 3 to 14 months. All patients underwent surgical treatment, except one patient who refused surgery. Eighty-seven patients underwent 90 surgical procedures: local excision, 9; coloanal anastomosis, 36; abdominoperineal resection, 4; Hartmann's procedure, 1. Isolated local recurrences occurred in five patients (4.3 percent) and combined local and distant failure in eight patients (6.7 percent). Ninety patients are alive and disease-free at a median follow-up of 36 months.Combined up-front chemoradiotherapy was associated with tolerable and acceptable side effects. A significant number of patients had complete disappearance of their tumors (30.5 percent) within a median follow-up of 36 months. This regimen spared 26.2 percent of patients from surgical treatment and allowed sphincter-saving management in 38.1 percent of patients who may have required abdominoperineal resection. Preliminary results of this trial suggests a reduction in the number of local recurrences and reinforces the concept that infiltrative low rectal cancer may be initially treated by chemoradiotherapy.