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Methotrexate levels and outcome in osteosarcoma
Author(s) -
Zelcer Shayna,
Kellick Michael,
Wexler Leonard H.,
Shi Weiji,
Sankaran Marie,
Lo Sarah,
Healey John,
Huvos Andrew G.,
Meyers Paul A.,
Gorlick Richard
Publication year - 2005
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.20314
Subject(s) - medicine , methotrexate , osteosarcoma , necrosis , chemotherapy , gastroenterology , surgery , pathology
Background Peak serum concentrations of methotrexate (MTX) have been reported to correlate with outcome in osteosarcoma (OS). Modification of the MTX dose to achieve peak levels between 700 and 1,000 µmol/L has been recommended. The goal of the study was to assess whether there is a correlation between histologic necrosis of the tumor and/or prognosis with peak MTX serum concentration. Procedure Treatment included multi‐agent adjuvant chemotherapy, including high‐dose MTX (12 g/m 2 ). Peak MTX levels were drawn following a 4‐hr infusion. Histologic evaluation for percent necrosis was done at the time of definitive resection. Results The median peak MTX level (n = 52 patients) was 1,060 µmol/L (range: 410–4,700 µmol/L), with significant intra‐patient and inter‐patient variability. Fifty‐eight percent of the levels were 1,000 µmol/L or higher. Response to pre‐operative chemotherapy was: 18% Grade I necrosis, 35% Grade II, 31% Grade III, and 16% Grade IV. No significant association was found between the mean peak MTX levels and necrosis ( P = 0.44). Event‐free survival (EFS) for the 48 patients with non‐metastatic disease at diagnosis was 76% at 4 years of follow‐up, with no association between the mean peak MTX level and EFS ( P = 0.24). Conclusions The absence of a demonstrable correlation between peak MTX levels and histologic necrosis or EFS may suggest that most patients achieve therapeutic levels when MTX is given at a dose of 12 g/m 2 . The significant degree of intra‐patient variability in peak levels poses a dilemma for pharmacokinetic adjustment. Continued use of HD‐MTX in all patients, rather than dose adapted therapy, may be justified. Pediatr Blood Cancer 2005;44:638–642. © 2005 Wiley‐Liss, Inc.