High dose methotrexate with CF rescue therapy in patients with head and neck cancer

: A clinical trial of high dose methotrexate (MTX)-CF rescue was conducted in 17 institutions. Forty-seven patients with head and neck cancer entered this trial, of which 29 were evaluable. In this series, the patients were divided into 2 groups (Arm I, Arm II), according to physician's selection. MTX was administered 700 mg/m2 (1000 mg/body) in Arm I and 1750 mg/m2 (2500 mg/body) in Arm II by i.v. drip over 6 hours. Twenty-four hours after initiation of MTX infusion, CF rescue was started. There was no complete response in 29 patients. Four patients showed partial response with an overall response rate of 13.8%. There were 4 partial responders out of 21 patients in Arm I, with a response rate of 19%, whereas there was no partial responders out of 8 patients in Arm II. These results showed no apparent dose response. MTX concentrations in plasma were determined at 6, 24, 48 and 72 hours after initiation of MTX infusion. The assay results revealed a safe range in Arm I, but exceeded in 3 cases of Arm II. GI disturbances were seen at the rate of 78%. Bone marrow suppression was remarkable and hepatic toxicity was observed as the rate of 41%. No renal toxicity was observed. The results of high dose MTX-CF rescue therapy were not better than those of moderate dose therapy, so that we concluded that MTX should be used as one agent at low or moderate dose in combination chemotherapy as far as Japanese patients with head and neck cancer are concerned.