Ifosfamide-Induced Fanconi's Syndrome

Abstract

Ifosfamide is an alkylating antineoplastic prodrug used to treat many solid tumors. The metabolism of ifosfamide is via CYP450 3A4 and 2B6 and produces active ifosfamide mustard, the toxic metabolite acrolein and chloroacetaldehyde (CAA). Additionally, CAA is believed to induce proximal tubular dysfunction which results in Fanconi's syndrome. It is a condition not commonly encountered in adults receiving ifosfamide but relatively common in children. Herein, we have reported a 25-year-old woman with a history of synovial sarcoma with multiple lung metastasis and repetitive locoregional recurrence. She received chemotherapy with high dose ifosfamide as her antineoplastic treatment. Before her 4th cycle of chemotherapy, the patient's pre-chemotherapy evaluation revealed proteinuria, glucosuria, phosphateuria, hypophosphatemia and non-anion gap metabolic acidosis. The above conditions were consistent with Fanconi's syndrome. We treated her with electrolyte supplement and close monitoring of the noted laboratory abnormalities. Fortunately, the laboratory abnormality gradually resolved. Our case highlights the rare potential complication of ifosfamide, especially in patients who had received a high cumulive dose. To avoid this rare but potentially debilitating condition, patients whose cumulative ifosfamide dose reaches threshold should be closely monitored.

Keywords

• Fanconi's syndrome
• ifosfamide
• chloroacetaldehyde (CAA)