High Dose Methotrexat Liver Toxicity

Abstract

Introduction: Methotrexate (MTX) is an anti folate drug that used in malignant and non malignant patients. The usage of high dose methotrexate was limited to patients with: Osteogenic sarcoma, Ewing sarcoma and Lymphoma. The aim this study was to determine the toxicity or side effects of very high dose methotrexate (8-10 gr/m²/cycle). This study is the first study in Iranian patients and one of few study in world wide with this dosage and number of patients.
Patients and methods: In a prospective study on all patients with osteogenic sarcoma, Ewing sarcoma , and lymphoma that candidate for high dose MTX (mean total dosage was 27 gr/m²/case without any underlying disease, and after full physical examination and performing necessary paraclinical tests (Na, K, BUN, Cr, Uric acid, AST, ALT, Bilirubin, and ECG entered and information was filled for all of them prior and after the every cycle. The follow up visit include: repeated physical examination and duration of its was at least 6 months.
Results: There were 102 cases, 60 cases were male (58.8%), 42 female (41.2%), median age was 19.5 (5-80), Osteogenic sarcoma and Ewing sarcoma 87 cases (49/male and 38/female), 15 cases were Lymphoma (11/male, 4/female). Total course of MTX therapy was 273 (median courses were 2.67/patient). Our result revealed: Abdominal pain due to hepatomrgally was not obsereved, rising in bilirubin and alkaline phosphetase were not observed, but rising in AST and ALT were the most common liver toxicity due to high dose MTX and detail were: this toxicity was in 23 cases (46.9%) [11/men (18.3%) and 12/female (28.6%)] respectively. The maximum toxicity was grade 2 toxicity according to NCI criteria. All of them resolved spontaneously without any specific management and treatment except watch and wait.
Conclusion: This study revealed that the usage of very high dose methotrexate had liver toxicity but these toxicities were limited to abnormal AST and ALT. All of these toxicities were transient and resolved without any scar on liver function after cessation of therapy. After at least 6 months follow up we didn’t see any abnormality.