title: 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.
mesh_terms: 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
chemical_list: D012709:Serum Albumin; D005492:Folic Acid; D003404:Creatinine; D008727:Methotrexate