Predefinitive and postdefinitive chemotherapy for locally advanced squamous carcinoma of the head and neck

Advanced squamous carcinoma of the head and neck remains refractory to the best combinations of surgery and radiotherapy. Weekly methotrexate in high doses with leucovorin "rescue" is able to produce significant remissions in a majority of patients treated palliatively for recurrent disease yet is associated with little or no toxicity. We have attempted to improve the cure of patients with advanced disease by the use of high dose methotrexate (3-7.5 g/M2) and leucovorin prior to and following definitive surgery and/or radiotherapy. In a series of 24 patients we have achieved a response rate of 52%, with minimal toxicity during chemotherapy, and no apparent potentiation of toxicity with radiotherapy. Survival free of disease appears to be prolonged in patients with response to this chemotherapy. Multimodality approaches to locally advanced squamous carcinoma of the head and neck may soon yield improved cure rates.