CONCOMITANT RADIOTHERAPY AND CHEMOTHERAPY IS SUPERIOR TO RADIOTHERAPYALONE IN THE TREATMENT OF LOCALLY ADVANCED ANAL CANCER - RESULTS OF APHASE-III RANDOMIZED TRIAL OF THE EUROPEAN ORGANIZATION FOR RESEARCH AND TREATMENT OF CANCER RADIOTHERAPY AND GASTROINTESTINAL COOPERATIVE GROUPS

Purpose: To investigate the potential gain of the concomitant use of r adiotherapy and chemotherapy in improving local control and reducing t he need for colostomy, a randomized phase III trial was performed in p atients with locally advanced anal cancer. Materials and Methods: From 1987 to 1994, 110 patients were randomized between radiotherapy alone and a combination of radiotherapy and chemotherapy. The patients had T3-4N0-3 or T1-2N1-3 anal cancer. Radiotherapy consisted of 45 Gy give n in 5 weeks, with a daily dose of 1.8 Gy. After a rest period of 6 we eks, a boost of 20 or 15 Gy was given in case of partial or complete r esponse, respectively. Surgical resection as part of the primary treat ment was performed if possible in patients who held not responded 6 we eks after 45 Gy or with residual palpable disease after the completion of treatment. Chemotherapy was given during radiotherapy: 750 mg/m(2) daily fluorouracil as a continuous infusion on days 1 to 5 and 29 to 33, and a single dose of mitomycin 15 mg/m(2) administered on day 1. R esults: The addition of chemotherapy to radiotherapy resulted in a sig nificant increase in the complete remission rate from 54% for radiothe rapy alone to 80% for radiotherapy and chemotherapy, and from 85% to 9 6%, respectively, if results are considered after surgical resections. This led to a significant improvement of locoregional control and col ostomy-free interval (P = .02 and P = .002, respectively), both in fav or of the combined modality treatment. The locoregional control rate i mproved by 18% at 5 years, while the colostomy-free rate at that time increased by 32% by the addition of chemotherapy to radiotherapy. No s ignificant difference was found when severe side effects were consider ed, although anal ulcers were more frequently observed in the combined -treatment arm. The survival rate remained similar in both treatment a rms. Skin ulceration, nodal involvement, and sex were the most importa nt prognostic factors for both local control and survival. These remai ned significant after multivariate analysis. The improvement seen in l ocal control by adding chemotherapy to radiotherapy also remained sign ificant after adjusting for prognostic factors in the multivariate ana lysis. Event-free survival, defined as free of locoregional progressio n, no colostomy, and no severe side effects or death, showed significa nt improvement (P = .03) in favor of the combined-treatment modality, The 5-year survival rate was 56% for the whole patient group. Conclusi on: The concomitant use of radiotherapy and chemotherapy resulted in a significantly improved locoregional control rate and a reduction of t he need for colostomy in patients with locally advanced anal cancer wi thout a significant increase in late side effects. (C) 1997 by America n Society of Clinical Oncology.