MITOMYCIN-C AS AN ADJUNCT TO POSTOPERATIVE RADIATION-THERAPY IN SQUAMOUS-CELL CARCINOMA OF THE HEAD AND NECK - RESULTS FROM 2 RANDOMIZED CLINICAL-TRIALS

Purpose: This study was undertaken to assess the benefit of mitomycin C as an adjunct to postoperative radiation therapy in patients with op erable squamous cell carcinoma of the head and neck. Methods and Mater ials: Between May 1980 and May 1991, 182 patients have been enrolled i n two consecutive randomized clinical trials testing mitomycin C as an adjunct to radiation therapy in squamous cell carcinoma of the head a nd neck. In both trials, patients were stratified by stage, disease si te and intent of therapy. This subset analysis includes 113 patients e ntered into these two randomized trials treated with surgery and posto perative radiation therapy. In the first trial, patients were randomiz ed to receive standard postoperative radiation therapy alone compared with postoperative radiation therapy with concomitant mitomycin C. In the second trial, patients were randomized to postoperative radiation therapy or postoperative radiation therapy with concomitant mitomycin C plus dicoumarol. Results: As of November 1991, the 113 patients trea ted with surgery and postoperative radiation therapy in both trials ha d a median follow-up of 93 months. There have been a total of 12 local recurrences in the radiation therapy alone arm compared to 0 local re currences in the radiation therapy/mitomycin C arm. There were eight r egional recurrences in the radiation therapy alone arm compared with f ive regional recurrences in the mitomycin C arm. Patients in the mitom ycin C arm experienced a superior 5-year actuarial local regional cont rol rate (87% vs. 67%, p < .015) and a statistically significant disea se-free survival benefit (67% vs. 44%, p < .03). Overall survival diff erence between the two arms (56% vs. 41%) has not reached statistical significance. Conclusions: We conclude from these prospectively design ed randomized clinical trials that in patients with operable head and neck cancer treated with surgery and postoperative radiation therapy, concomitant administration of mitomycin C with radiation therapy will result in a statistically significant disease-free survival and local regional control benefit. We are currently investigating the value of other bioreductive alkylating agents as adjuncts to radiation therapy in patients with squamous cell carcinoma of the head and neck.