High-dose methotrexate for osteosarcoma: toxicity and clinical results.
9 patients with osteosarcoma were treated with a total of 122 infusions of high-dose methotrexate (MTX; 140-350 mg/kg) followed by leucovorin rescue. Plasma kinetics of MTX and 7-hydroxymethotrexate (7-OH-MTX) has been routinely monitored. Due to inadequate hydration and alkalinization, 1 of the 122 high-dose MTX infusions was followed by delayed disappearance of MTX and 7-OH-MTX from plasma with subsequent development of severe mucositis. Serious hepatotoxicity repeatedly developed in another patient with inconspicuous MTX kinetics. The benefit of monotherapy with high-dose MTX for adjuvant treatment of osteosarcoma remains questionable, since 6 of 8 patients with primary osteosarcoma developed pulmonary metastases within 4-12 months (median 5 months), 2 have been disease-free and alive for 25 and 53 months.
D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000188:drug therapy*; D056486:Chemical and Drug Induced Liver Injury; D005260:Female; D006801:Humans; D007700:Kinetics; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives / Q000097:blood; D008875:Middle Aged; D009092:Mucous Membrane / Q000187:drug effects; D012516:Osteosarcoma / Q000188:drug therapy*
D002955:Leucovorin; C011864:7-hydroxymethotrexate; D008727:Methotrexate