The variability of individual tolerance to methotrexate in cancer patients.
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.
D000328:Adult; D000367:Age Factors; D000368:Aged; D000505:Alopecia / Q000139:chemically induced; D001806:Blood Urea Nitrogen; D001835:Body Weight; D056486:Chemical and Drug Induced Liver Injury; D003231:Conjunctivitis / Q000139:chemically induced; D003404:Creatinine / Q000097:blood; D003967:Diarrhea / Q000139:chemically induced; D003875:Drug Eruptions / Q000209:etiology; D005492:Folic Acid / Q000097:blood; D006801:Humans; D007275:Injections, Intravenous; D007970:Leukopenia / Q000139:chemically induced; D008727:Methotrexate / Q000008:administration & dosage / Q000633:toxicity*; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D012709:Serum Albumin / Q000032:analysis; D013280:Stomatitis / Q000139:chemically induced; D013921:Thrombocytopenia / Q000139:chemically induced; D013997:Time Factors; D014839:Vomiting / Q000139:chemically induced
D012709:Serum Albumin; D005492:Folic Acid; D003404:Creatinine; D008727:Methotrexate