CONCOMITANT RADIOCHEMOTHERAPY WITH CISPLA TIN (CDDP), 5-FLUOROURACIL (5-FU) AND MITOMYCIN-C (MMC) IN LOCALLY ADVANCED OROPHARYNGEAL CARCINOMA - RESULTS OF A PHASE-II TRIAL

In order to improve loco-regional control in locally advanced orophary ngeal carcinoma, a phase II trial was designed to establish the feasib ility of concomitant conventional radiotherapy and three cycles of che motherapy at day 1, 21 and 42 with cisplatin (CDDP) 20 mg/m(2) and 5-f luorouracil (5-FU) 400 mg/m(2) day 1 to day 4, and mitomycin C (MMC) 1 0 mg/m(2) day 1. From March 1990 to September 1993, 27 patients (mean age: 55) were included in this study. Three patients (11%) were T2NO, 19 (70%) T3 (T3NO: n = 9, T3N1: n = 1, T3N2: n = 5, T3N3: n = 4), and 5 (19%) T4 (T4NO: n = 1, T4N1: n = 1, T4N2: n = 2, T4N3: n = 1). With a mean follow-up of 34 months (17-59), ten patients (37%) were alive, free of disease; among the 17 other patients, seven died with cancer. Loco-regional control rate was 85%. One and 2-year survival rates were respectively 48 and 31% for overall and disease-free survival; respec tive corrected overall survival rates were 68 and 61%. Grade 3 or 4 mu cositis was 81%; enteral feeding was necessary for 63% of the patients ; mean loss of weight was 5.7 kg. Grade > 2 thrombopenia occured in 11 patients (41%), grade > 2 neutropenia in eight patients (29%), grade > 2 anemia in four patients (15%). Febrile neutropenia or aplasia occu red in five patients (19%). Two patients (7%) died during treatment of haematological or infectious complications related to the treatment. Another patient died 2 months after treatment with grade 4 thrombopeni a and septicemia. Addition of MMC to 5-FU and CDDP might have been par tly responsible of this increased toxicity. A high complete response r ate has been achieved with this concomitant radio-polychemotherapy, bu t with a severe digestive and haematological toxicity, which did nor a llow to conclude to the feasiblity of this therapeutic association.