Clinical and Experimental Evaluation of Urinary Histidine Derivatives as an Index of Folic Acid Metabolism:II. The Observation in Neoplastic Diseases with or without Methotrexate Administration

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Urinary excretion of formiminoglutamic acid (FIGLU) and urocanic acid was observed in patients with various neoplastic diseases. Using these histidine derivatives as an index, serial observations have been made mainly on the toxic effect of several dose schedules of methotrexate (MTX) in tumor-bearing patients and normal animals. The dosage schedules of MTX comprised a single large dose, intermittent large doses, and arterial infusion in patients and a single large dose and divided doses in animals.Of 40 untreated patients with various neoplastic diseases, 19 excreted an abnormal amount of FIGLU, 11 of urocanic acid, and 20 of the combined derivatives in the urine. The serial observations of urinary histidine derivatives under MTX treatment revealed following evidences; (a) the excreted amount of the derivatives in maximum level was well proportional to the size of dose of MTX in single injection, (b) the severity of the clinical signs, the toxicity of MTX, was in parallel with the amount of the derivatives excreted in the urine, and (c) the beginning of increase of the derivatives preceded that of decrease in white blood cell count, if accompanied, in all the cases.
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