A 56-year-old woman comes to the emergency department due to 3 days of frequent urination, suprapubic pain, dysuria, and progressive hematuria. She has had no fevers or chills. The patient has a history of lymph-node-positive breast cancer that was diagnosed following a routine mammogram. A month ago, she began treatment with systemic chemotherapy. Temperature is 37.1 C (98.8 F). Suprapubic tenderness is present on abdominal examination. Hemoglobin is 9.8 g/dL. Urinalysis shows numerous red blood cells but no leukocyte esterase or bacteria. Which of the following could have prevented this patient's current condition?
This patient who recently received systemic chemotherapy for breast cancer and now has progressive hematuria and suprapubic tenderness most likely has hemorrhagic cystitis caused by a nitrogen mustard-based chemotherapeutic agent, such as cyclophosphamide or one of its analogs (eg, ifosfamide). These agents are metabolized by the kidneys into acrolein, which is then excreted in the urine. Acrolein is toxic to uroepithelial cells and can cause cell death and necrosis if allowed to be in contact with these cells for a prolonged period.
Hemorrhagic cystitis associated with nitrogen mustard-based chemotherapy can be prevented by aggressive hydration and the coadministration of mesna (2-mercaptoethanesulfonate), a sulfhydryl compound that binds and inactivates the toxic metabolites of the chemotherapeutic agents in the urine.
(Choice A) Dexrazoxane is an iron-chelating agent that can help prevent anthracycline-induced (eg, doxorubicin) cardiotoxicity.
(Choice B) Filgrastim is a granulocyte colony-stimulating factor (G-CSF) analog used to stimulate the proliferation and differentiation of granulocytes in patients with neutropenia, as can occur after chemotherapy. This patient is afebrile, and her urinalysis is not suggestive of a urinary tract infection.
(Choice C) Leucovorin, or folinic acid, is a drug used in the treatment of methotrexate overdose. It also enhances the cytotoxic action of 5-fluorouracil (5-FU) and is used in combination with 5-FU in some cases of colorectal cancer.
(Choice E) Ondansetron inhibits serotonin 5-HT3 receptors and is used primarily to treat nausea and vomiting following chemotherapy.
Educational objective:
Hemorrhagic cystitis during therapy with cyclophosphamide or ifosfamide is caused by the urinary excretion of the toxic metabolite acrolein. It can be prevented by aggressive hydration, bladder irrigation, and administration of mesna, a sulfhydryl compound that binds acrolein in the urine.