Prospective randomized trial of one-hour sequential versus simultaneous methotrexate plus 5-fluorouracil in advanced and recurrent squamous cell head and neck cancer.

Results from experimental systems suggest that the combination of methotrexate (MTX) and 5-fluorouracil (5-FU) produces synergistic cytotoxic effects that are dependent on the sequence of drug administration. Biochemical studies have demonstrated plausible mechanisms of a synergistic effect when MTX precedes 5-FU. A variety of phase I and phase II studies have employed this sequential combination with promising but inconclusive results. In this …