COMPARISON OF INTRAVENOUS AND ORAL HIGH-DOSE METHOTREXATE IN TREATMENT OF SOLID TUMORS

An outpatient regimen of oral high-dose methotrexate was studied in 14 patients with solid tumours over 12 months. Detailed pharmacokinetic analysis in five patients showed high oral bioavailability (mean±SE of mean 87.6±15%), indicating that with this regimen oral methotrexate was well absorbed and the first-pass effect low. Oral administration resulted in peak plasma methotrexate concentrations of 8.4±0.5 (µmol/1 (382 ±23 µg/100 ml) and was almost as effective as intravenous administration, which achieved peak concentrations of 9.9±0.4µmol/1 (450±18 µg/100 ml). In all 14 patients the clinical response to oral treatment was comparable to that reported to intravenous administration of high-dose methotrexate used in combination with other cytotoxic drugs. The disease-free interval in cases of adult sarcoma was 7–4 ±1.3 months and the relapse rate 29%. Out of four patients with small-cell carcinoma, two showed an objective response to oral treatment. We suggest that oral high-dose methotrexate given in divided doses is a rational alternative to expensive intravenous high-dose methotrexate regimens, but further clinical evaluation is necessary. © 1979, British Medical Journal Publishing Group. All rights reserved.