Survival after unexpected high serum methotrexate concentrations in a patient with osteogenic sarcoma

An 18-year-old female patient receiving adjuvant chemotherapy for osteogenic sarcoma developed a pruritic erythematous rash during infusion of the eighth dose of methotrexate (8 g/m2) in the series. In other respects, the infusion proceeded normally but the 24-hour serum concentration of methotrexate was unexpectedly and extremely high, 574 mumols/L. Dosing error was excluded, as was the hypothesis that the high concentrations were due to the presence of methotrexate-specific antibodies. Acute oliguria and renal failure were the primary manifestations of the drug-induced toxicity and the high concentrations can be attributed to decreased renal elimination of the drug over the first 24 hours. Treatment consisted of folinic acid rescue, forced diuresis, sequential charcoal haemoperfusion and haemodialysis, and repeated oral doses of activated charcoal. After examination of the contribution of the extracorporeal procedures and the charcoal to the elimination of the drug, the relative lack of morbidity was attributed primarily to the folinic acid rescue and the intensive supportive care.