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 a s the preferred treatment of epidermoid carcinoma of the anal canal. T o determine the importance of mitomycin (MMC) in the standard CR regim en 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 and Methods: Between August 1988 and December 1 991, 310 patients were randomized to receive either radiotherapy (RT) and fluorouracil (5-FU) or radiotherapy, 5-FU, and MMC. Of 291 assessa ble patients, 145 received 45 to 50.4 Gy of pelvic RT plus 5-FU at 1,0 00 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 posttreatme nt biopsy were treated with ct salvage regimen that consisted of addit ional pelvic RT (9 Gy), 5-FU, and cisplatin (100 mg/m(2)). Results: Po sttreatment biopsies were positive in 15% of patients in the 5-FU arm versus 7.7% in the MMC arm (P = .135). At 4 years, colostomy rates wer e lower (9% v 22%; P = .002), colostomy-free survival higher (71% v 59 %; P = .014), and disease-free survival higher (73% v 51%; P = .0003) in the MMC arm. A significant difference in overall survival has not b een observed at 4 years. Toxicity was greater in the MMC arm (23% v 7% grade 4 and 5 toxicity; P less than or equal to .001). Of 24 assessab le patients who underwent salvage CR, 12 (50%) were rendered disease-f ree. Conclusion: Despite greater toxicity, the use of MMC in a definit ive CR regimen for anal cancer is justified, particularly in patients with large primary tumors. Salvage CR should be attempted in patients with residual disease following definitive CR before resorting to radi cal surgery. (C) 1996 by American Society of Clinical Oncology.