High-dose methotrexate treatment and liver function in patients with osteosarcoma.
OBJECTIVE
To study the effects of short-term high-dose methotrexate therapy on liver function in patients with osteosarcoma.


METHODS
Open prospective study.


METHODS
Department of Internal Medicine and Oncology, Istituto Ortopedico Rizzoli, Bologna, Italy.


METHODS
Fourteen patients with osteosarcoma, with no evidence of previous or actual liver disease at the time of diagnosis.


METHODS
All patients received a cumulative dose of 30-57 gm-2 of methotrexate within 6 months as neo-adjuvant chemotherapy (pre- and post-surgery). Each course of chemotherapy included methotrexate at a dose of 8-12 gm-2 and, in addition, adriamycin and cisplatinum.


METHODS
Galactose elimination capacity and antipyrine clearance were measured at baseline, after the first course of chemotherapy, at the end of the pre-operative period and at the end of chemotherapy. In each case they were carried out after transaminase levels had returned to normal.


RESULTS
Galactose elimination capacity decreased from 2.45 (+/- 0.48) mM min-1 to 2.04 (+/- 0.60) mM min-1 after the five planned courses of chemotherapy (P = 0.013, Wilcoxon signed-rank test), without any change in routine liver function tests. No differences in antipyrine clearance and half-life were demonstrated (n = 8).


CONCLUSIONS
The data are consistent with a decreased reserve capacity of the liver after short-term, high-dose methotrexate. Long-term survivors deserve monitoring of liver function for safer methotrexate use, in the light of progressive dosage increments to improve prognosis in neoplastic diseases.
Fabbri
A
A
Institute of Internal Medicine, University of Bologna, Italy.
Motta
E
E
Ferrari
S
S
Longhi
C
C
Marchi
E
E
Bacci
G
G
Figus
E
E
Marchesini
G
G
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000983:Antipyrine / Q000493:pharmacokinetics*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D002945:Cisplatin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005690:Galactose / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008111:Liver Function Tests; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000494:pharmacology*; D012516:Osteosarcoma / Q000188:drug therapy / Q000378:metabolism*; D011446:Prospective Studies
D004317:Doxorubicin; D002945:Cisplatin; D000983:Antipyrine; D005690:Galactose; D008727:Methotrexate