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

Abstract

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.