Methotrexate treatment of advanced head and neck cancers: a dose response evaluation.

Fifty-eight patients with advanced squamous cell cancer of the head and neck have been randomized on a study comparing three different weekly methotrexate (MTX) dose levels followed at 24 hours by standardized folinic acid rescue. Eighteen patients received MTX 5 g/m2, 24 patients received 500 mg/m2, and 16 patients received 50 mg/m2. The initial response rate according to treatment were 50%, 21% and 31%, respectively. Six patients crossed from low- to medium-dose MTX after failing to respond (four) or relapsing, and one in each group had a tumor response. Eleven patients crossed over from initial medium-dose to high-dose MTX after failing to respond (ten) or relapsing, and one in each group had a tumor response. The median time to maximum response was 3.5 weeks. There were only two complete responders, and one is disease free more than 19 months after starting treatment and more than 15 months after stopping treatment. The high-dose MTX treatment was significantly more toxic than lower doses, and there were four drug-related deaths (three in the high-dose group). The preliminary results of this study support the notion of a dose-response relationship to MTX in advanced squamous cell cancer of the head and neck.