Methotrexate and 5-fluorouracil in head and neck cancer.

Since experimental data strongly suggest a synergistic cytotoxic effect when methotrexate (MTX) and 5-fluorouracil (5-FU) are administered sequentially, we investigated antitumor effects and toxicity with sequential MTX/5-FU followed by leucovorin rescue in 52 patients with carcinoma of the head and neck. MTX (200 mg/m2) was given as an i.v. infusion over 1 hr. At 2 hr, 5-FU (600 mg/m2) was started as an i.v. infusion for 2 hr. At 24 hr, the leucovorin rescue was started. The chemotherapy course was repeated every week until toxicity (mainly gastrointestinal) occurred, after which the interval between courses was prolonged to 2 wk. Toxicity was mild and usually disappeared when the interval between the chemotherapy courses was prolonged to 2 wk. The regression rate was 15% for complete and 48% for partial regression (response rate, 63%). In 31 of the patients not previously treated, the objective response rate was 74%. About the same results were obtained for tumors of different anatomic sites of the head and neck. Radiotherapy could be added sequentially without measurable escalation of toxicity. We conclude that sequential MTX/5-FU treatment, which produces a very mild toxicity to normal tissue, is effective in inducing antitumor response in patients with carcinoma of the head and neck.