Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study.

Purpose: Definitive chemoradiation (CR) has replaced radical surgery as the preferred treatment of epidermoid carcinoma of the anal canal. To determine the importance of mitomycin (MMC) in the standard CR regimen and to assess the role of salvage CR in patients who have residual tumor following CR, a phase III randomized trial was undertaken by the Radiation Therapy Oncology Group (RTOG)/Eastern Cooperative Oncology Group (ECOG). Patients andMethods: Between August 1988 and December 1991, 310 patients were randomized to receive either radiotherapy (RT) and fluorouracil (5-FU) or radiotherapy, 5-FU, and MMC. Of 291 assessable patients, 145 received 45 to 50.4 Gy of pelvic RT plus 5-FU at 1,000 mg/m 2 /d for 4 days, and 146 received RT, 5-FU, and MMC (10 mg/m 2 per dose for two doses). Patients with residual tumor on posttreatment biopsy were treated with a salvage regimen that consisted of additional pelvic RT (9 Gy), 5-FU, and cisplatin (100 mg/m 2 ). E PIDERMOID CARCINOMAS of the anal region I comprise only 1% to 2% of large bowel cancers and 3.9% of anorectal carcinomas.' Nevertheless, these neoplasms have dramatically increased in importance over the past 20 years as a model for organ preservation with the use of concomitant radiation (RT) and chemotherapy in lieu of radical surgery. 2 Before the application of chemoradiation (CR) regimens, the 5-year survival rate of patients with anal epidermoid malignancies managed by radical surgery ranged from 40% to 60% and local relapse was common.34 The combined modality regimen initially described by Nigro et a 5 in 1974 was a preoperative regimen that subsequently evolved into a definitive treatment program by 1983.67 More than 500 patients treated with CR using fluorouracil (5-FU) infusion and mitomycin (MMC) have been reported over the past 18 years. 6 ' 2