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The Use of Leucovorin Orally in Normal and Leukemic L1210 Mice to Prevent the Toxicity and Gastrointestinal Lesions Caused by High Doses of Methotrexate

Cancer Chemotherapy National Service Center, Chemotherapy, National Cancer Institute, Bethesda, Maryland 20014

Leucovorin p.o. was as effective as parenterally in preventing weight loss and toxic deaths in normal mice from high doses of methotrexate. Histological sections of proximal jejunum demonstrate the protection afforded by delayed p.o. leucovorin from the marked disruption of villi and mucosal glands produced by methotrexate. Mice bearing leukemia L1210 treated with methotrexate plus leucovorin p.o. were able to tolerate 2- to 4-fold increases in the dose of methotrexate tolerated by mice treated with methotrexate alone. This resulted in a greater increase in survival time of leukemic mice. The therapeutic advantage of the regimen of delayed leucovorin given in conjunction with methotrexate is maintained when leucovorin is administered p.o.

Received 8/15/69. Accepted 11/19/69.

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