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Toxicity and Antitumor Effect Of Divided Doses of Methotrexate

WILLIAM R. VOGLER, MD; CHARLES M. HUGULEY JR., MD; WILSON KERR, MD
Arch Intern Med. 1965;115(3):285-293. doi:10.1001/archinte.1965.03860150029006.
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IT IS generally agreed that single daily doses of folic acid antagonists given by mouth for prolonged periods are usually ineffective in the treatment of solid tumors.1-5 Since the successful treatment of women with choriocarcinoma by Li et al and Hertz et al6-9 with large daily oral, intravenous or intramuscular doses of methotrexate, there has been renewed interest in dosage schedules and routes of administration.10-12 Repeated courses in large oral doses (up to 25 mg for five days),13 single intravenous injections (2.5-15 mg/kg),14 or continuous intra-arterial infusions (50 mg/24 hours)10 produced objective responses in solid tumors more frequently than previously noted.

In addition to these clinical observations there has been considerable advance in knowledge of the pharmacology of methotrexate recently. It has been reviewed in detail by several authors.15-18 It seemed appropriate to us to attempt to apply this new pharmacologic knowledge to

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