1248 Use of methylene blue and bicarbonate in ifosfamide-related CNS toxicity. Case report

Severe sometimes fatal CNS toxicity is a rare, dose-related side effect of ifosfamide (IFO). It has been suggested to be due to toxic effects of IFO metabolites on electron transport. Methylene blue (MB) has been tested in a few patients as an antidote. We have treated 2 adults with MB, who presented with severe IFO-related CNS toxicity. The 1st patient received combination chemotherapy for Wilms-Tumor containing 3.5 g IFO i. v for 3 days. On day 1 of IFO infusion, he developed paranoid hallucinations, agitation and coma (CTC grade 4) for 3 days. With 5 further cycles of an equal chemotherapy he received 50 mg MB 4 × /d i.v. His urine pH was kept above 7.0 with i. v bicarbonate. No CNS toxicity was observed. The 2nd patient was treated with PEl for testicular cancer, containing only Ig IFO for 4 days because of preexisting renal failure. On day 1, he developed paranoia, agitation and disorientation (CTC grade 3). IFO was continued together with MB and bicarbonate as described. All CNS symptoms resolved within 48 h. We conclude, that iv administration of MB might be effective against IFO-related CNS toxicity. A phase II trial is currently being conducted.