The effects of high dose methotrexate in patients with neoplastic diseases: a prospective study

Background: Methotrexate (MTX) is one of the most widely used anti-cancer agents. The administration of a high-dose methotrexate (HD-MTX) can be safely administered to patients with normal renal function, using alkalinization, hydration, and pharmacokinetically guided leucovorin (LV) rescue. The aim of this study was to determine the side effects of HD-MTX in patients with for neoplastic diseases. Methods: In a prospective study on all admitted patients in Hematology and Oncology Ward, receiving MTX for chemotherapy and without any other underlying disease, after full physical examination and performing necessary paraclinical exams (Na, K, Ca, BUN, Cr, Uric acid, SGOT, SGPT, bilirubin and ECG), the information form was filled for all at admission and in follow up visits to be used in a final assessment. Renal and hepatic function was assessed at the beginning of chemotherapy and systematically during subsequent cycles on the basis of available laboratorymethods. The follow up included liver and renal function and other necessary laboratory tests. Results: There were 98 cases, 48 of whom suffered from acute lymphoblastic leukemia and received high dose MTX (at least 2.5 gr) and 50 with choriocarcinoma received at least 800 mg per cycle. 31 cases were male and 67 female. The mean age was 26.4 years. The most common side effects were nausea and vomiting in 28 cases (28%). Hepatotoxicity (a rise in alanine aminotransferase > two to three times of the upper limit of normal) was not observed in any patient. Nephrotoxicity (at least 30% increase in BUN or creatinine or 30% rise in creatinine clearance) was not observed. In 8 patients, a rise in alanine aminotransferase less than two times the upper limit of normal was noticed. All these minor abnormalities were resolved in closed follow ups. None developed bone marrow suppression, serum electrolyte imbalance, and severe allergic reactions. Conclusion: Our study revealed that MTX side effects in southern Iran were minimal and toxicity was absent at the end of treatment. The side effects of MTX should be revised in different populations with different genetic and HLA profile.