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. 1971 Jun;25(2):298–305. doi: 10.1038/bjc.1971.38

The Variability of Individual Tolerance to Methotrexate in Cancer Patients

H H Hansen, O S Selawry, J F Holland, C B McCall
PMCID: PMC2008449  PMID: 4256007

Abstract

Individual tolerance to single or widely spaced doses of methotrexate was explored in 49 patients with advanced cancer with normal serum creatinine and/or blood urea nitrogen. Methotrexate was given as an intravenous infusion over 1 hour at initial doses of 80-120 mg./m2 body surface area. The doses were increased by 50% increments every 2 weeks until moderate toxicity occurred, arbitrarily defined as leukopenia <5000/mm.3, and/or thrombocytopenia <100,000/mm.3, and/or the appearance of oral mucous or intestinal toxicity.

The individual dose required to produce initial evidence of toxicity varied by a factor of 18 between 50 and 900 mg./m2. Starting doses above 80 mg./m2 were potentially hazardous. Dose limiting toxicity consisted of leukopenia with or without stomatitis in 81% of the patients, and stomatitis without leukopenia, in 19%. Thrombocytopenia was seen in 19% of the patients, but was never a dose limiting factor alone. Leukopenia always preceded thrombocytopenia. The nadir for haematologic toxicity varied considerably between day 5-15 and 9-14 for leukocytes and platelets, respectively, while oral ulcerations, when they occurred, consistently began between days 3-6 after drug administration. Other toxic manifestations included dermatologic changes in 8 patients, hepatic dysfunction in 7, conjunctivitis in 7, nausea and vomiting in 6, alopecia in 4, and diarrhea in 3 patients.

The only factor which predicted toxicity was the patient's age. Drug tolerance was independent of previous chemotherapy or radiotherapy, weight loss, serum albumin or pretreatment serum folic acid levels.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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