High-dose methotrexate treatment and liver function in patients with osteosarcoma.

OBJECTIVES

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

DESIGN

Open prospective study.

SETTING

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

SUBJECTS

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

INTERVENTIONS

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.

MAIN OUTCOME MEASURES

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.