A randomized study of accelerated fractionation radiotherapy with and without mitomycin C in the treatment of locally advanced head and neck cancer.

Objectives: This single-institution study evaluates the feasibility of accelerated fractionation radiotherapy (AF) with and without mitomycin C (MMC) in the treatment of locally advanced head and neck cancer.

Patients And Methods: Between May 1998 and October 2001, sixty patients with locally advanced stage III and IV of head and neck cancer were randomized into three treatment arms: (1) conventional fractionation radiotherapy (CF) (5 fractions per week); (2) accelerated fractionation radiotherapy (AF) (6 fractions per week); and (3) AF plus Mitomycin C (MMC).

Results: The 2-year overall survival (OS) of the whole group was 21%. The OS according to treatment arm was 23%, 20%, and 28% in CF, AF, and AF+MMC arms respectively (p<0.19). The 2-year loco-regional control (LC) rate was 22% for the whole group of patients. The LC was 10%, 25%, and 30% for the CF, AF, and AF+MMC respectively (p=0.27). The only significant parameters for OS and LC were performance status and pre-treatment hemoglobin level. Mucositis grades 3 & 4 occurred in 70% and 90% of the patients in the AF and AF+MMC arm respectively compared to 55% of patients in the CF arm (p=0.04). However the addition of MMC did not significantly increase the incidence or severity of mucositis between AF and AF+MMC (p=0.13). Hematological toxicity grades 3 & 4 were significantly higher after MMC (occurred in 40% of patients versus 10% and 5% in CF and AF arms respectively, p=0.04). There was no statistically significant difference in the incidence of grade 3 dryness of mouth (p=0.06), fibrosis (p=0.6), or lymphoedema (p=0.39) among the three arms.

Conclusion: There was a trend for improvement of LC and OS rates with the use of AF and the addition of MMC to AF compared to CF radiotherapy, although the difference was not statistically significant. The small number of the patients in each treatment arm and the inclusion of multiple tumor sites may contribute to these statistically insignificant results. Accordingly we advise 85 to continue the trial with inclusion of a larger number of patients and restrict tumor sites to one major site.