Severe renal toxicity due to intermediate-dose methotrexate

Methotrexate (MTX) is a drug widely used in the treatment of patients with malignant disease. Its well-known side effects include myelosuppression, mucositis and renal damage. These problems are primarily dose-related, tending to occur more frequently when high doses (greater than 1 g/m2) are given. We present four cases in whom severe renal and mucosal toxicity occurred with intermediate doses (200 mg/m2) of MTX despite folinic acid rescue. Possible reasons for this occurrence are discussed and means of avoiding such toxicity are suggested. Three of four patients developed severe loin pain within a few hours of injection; the significance of this symptom in relation to subsequent renal toxicity has implications for early recognition of the problem.