EPIDERMOID ANAL CANCER - RESULTS FROM THE UKCCCR RANDOMIZED TRIAL OF RADIOTHERAPY ALONE VERSUS RADIOTHERAPY, 5-FLUOROURACIL, AND MITOMYCIN

Background Non-surgical management of anal cancer by radiotherapy alon e or combined with chemotherapy has, in uncontrolled studies, yielded similar local tumour control and survival rates to surgery. However, w hether the addition of chemotherapy improves outcome without adding to morbidity is not known. Our trial was designed to compare combined mo dality therapy (CMT) with radiotherapy alone in patients with epidermo id anal cancer. Methods From 856 patients considered for entry to our multicentre trial, 585 patients were randomised to receive initially e ither 45 Gy radiotherapy in twenty or twenty-five fractions over 4-5 w eeks (290 patients) or the same regimen of radiotherapy combined with 5-fluorouracil (1000 mg/m(2) for 4 days or 750 mg/m(2) for 5 days) by continuous infusion during the first and the final weeks of radiothera py and mitomycin (12 mg/m(2)) on day 1 of the first course (295 patien ts). We assessed clinical response 6 weeks after initial treatment: go od responders were recommended for boost radiotherapy and poor respond ers for salvage surgery. The main endpoint was local-failure rate (gre ater than or equal to 6 weeks after initial treatment); secondary endp oints were overall and cause-specific survival. Analysis was by intent ion-to-treat. Findings In the radiotherapy and CMT arms, respectively, five and three were ineligible, and six and nine died 6 weeks after i nitial treatment. After a median follow-up of 42 months (interquartile range 28-62), 164 of 279 (59%) radiotherapy patients had a local fail ure compared with 101 of 283 (36%) CMT patients. This gave a 46% reduc tion in the risk of local failure in the patients receiving CMT (relat ive risk 0.54, 95% CI 0.42-0.69, p<0.0001). The risk of death from ana l cancer was also reduced in the CMT arm (0.71, 0.53-0.95, p=0.02). Th ere was no overall survival advantage (0.86, 0.67-1.11, p=0.25). Early morbidity was significantly more frequent in the CMT arm (p=0.03), bu t late morbidity occurred at similar rates. Interpretation Our trial s hows that the standard treatment for most patients with epidermoid ana l cancer should be a combination of radiotherapy and infused 5-fluorou racil and mitomycin, with surgery reserved for those who fail on this regimen.