title: Methotrexate serum concentration and histological response to multiagent primary chemotherapy for osteosarcoma of the limbs.
abstract: The authors investigated the influence of methotrexate (MTX) serum concentration on (histologically evaluated) tumor necrosis, induced by a primary multiagent chemotherapy, including MTX, for osteosarcoma. MTX serum peaks in 151 patients, preoperatively treated with MTX (8-12g/m2), cisplatin (120mg/m2) and Adriamycin (60mg/m2), were analyzed. Significantly (p < 0.01) higher serum MTX mean peaks were observed in patients with complete tumor necrosis (MTX 773.8 mumol/l) compared to patients with 90-99% tumor necrosis (639.8 mumol/l), 50-89% tumor necrosis (649.1 mumol/l) or less than 50% tumor necrosis (610 mumol/l). Complete tumor necrosis was observed in 9% of patients with MTX peaks of less than 600 mumol/l, in 27% of patients with serum MTX peaks between 600 and 699 mumol/l and in 37% of those with MTX peaks ranging from 700 to 799 mumol/l. Higher MTX peaks (800-899, 900-999, > 1000 mumol/l) were not associated with a further increase of cases with complete tumor necrosis. 40% of patients with an MTX peak greater than 700 mumol/l had complete tumor necrosis, compared to 15.5% of patients who did not reach this value (p < 0.002). At a multivariant analysis including age, sex, tumor site and volume, pretreatment serum alkaline phosphatase and lactic dehydrogenase levels, MTX peaks of 700 mumol/l and, less significantly, the histologic type (telangiectatic osteosarcoma), were independent factors influencing tumor necrosis. The authors conclude that MTX serum peaks significantly influence chemotherapy-induced tumor necrosis in osteosarcoma. In a primary treatment consisting of cisplatin, Adriamycin and MTX, complete tumor necrosis can be obtained in 40% of patients with MTX peak concentrations > or = 700 mumol/l.
authors.affiliation: Sezione di Chemioterapia dei Tumori dell' Apparato Locomotore, Università di Bologna, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Bacci
authors.forename: S
authors.initials: S
authors.lastname: Ferrari
authors.forename: P
authors.initials: P
authors.lastname: Picci
authors.forename: C
authors.initials: C
authors.lastname: Zolezzi
authors.forename: F
authors.initials: F
authors.lastname: Gherlinzoni
authors.forename: D
authors.initials: D
authors.lastname: Iantorno
authors.forename: A
authors.initials: A
authors.lastname: Cazzola
mesh_terms: D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000097:blood*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005121:Extremities; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000097:blood*; D012516:Osteosarcoma / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D011379:Prognosis
chemical_list: D000964:Antimetabolites, Antineoplastic; D004317:Doxorubicin; D002945:Cisplatin; D008727:Methotrexate