The Variability of Individual Tolerance to Methotrexate in Cancer Patients

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./m 2 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./m 2 . Starting doses above 80 mg./m 2 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.

Herpes simplex in oral ulcers in neutropenic patients

“…These include malignant infiltration, tissue necrosis secondary to vascular occlusion, anti-metabolite effects of chemotherapy or radiotherapy and infective agents (Hansen et al, 1971;Wray et al, 1980;Rand et al, 1982). The diversity of micro-organisms isolated has generated considerable debate as to their significance.…”

Moderate-Dose Methotrexate in Head and Neck Cancer

“…Previous reports have shown such a dose to be safe when given by intra venous push [33,34]. Tumor shrinkage with this schedule was rapid and correlated well with subjective relief from pain or trismus.…”

Postoperative Chemotherapy for Gastric Cancer in the Elderly

“…There are physiologic changes which affect metabolism and turnover of anticancer drugs in the elderly [17][18][19], A study done by Hansen et al [20] indicated an increased susceptibility in the elderly to hematologic toxicity induced by methotrexate. The reduction in renal func tion may explain the adverse effect of metho trexate in the elderly [21].…”