Methotrexate Serum Concentration and Histological Response to Multiagent Primary Chemotherapy for Osteosarcoma of the Limbs
Authors: Bacci, G.; Ferrari, S.; Picci, P.; Zolezzi, C.; Gherlinzoni, F.; Iantorno, D.; Cazzola, A.
Source: Journal of Chemotherapy, Number 6, December 1996 , pp. 472-478(7)
Publisher: Maney Publishing
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 (120 mg/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 umol/1) compared to patients with 90-99% tumor necrosis (639.8 umol/1), 50-89% tumor necrosis (649.1 μmol/1) or less than 50% tumor necrosis (610μmol/l). Complete tumor necrosis was observed in 9% of patients with MTX peaks of less than 600μmol/l, in 27% of patients with serum MTX peaks between 600 and 699μmol/l and in 37% of those with MTX peaks ranging from 700 to 799μmol/l. Higher MTX peaks (800-899, 900-999, >1000μmol/l) were not associated with a further increase of cases with complete tumor necrosis. 40% of patients with an MTX peak greater than 700 μmol/1 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 umol/1 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 > 700 μmol/1.
Document Type: Research Article
Publication date: 1996-01-01