How is chemotherapy-induced hemorrhagic cystitis treated?

Updated: Dec 15, 2020
  • Author: Joseph Basler, MD, PhD; Chief Editor: Edward David Kim, MD, FACS  more...
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Cyclophosphamide and ifosfamide toxicity can be minimized with hydration [18] and with the concurrent use of the following drugs:

  • 2-Mercaptoethanesulfonate (mesna [Mesnex]) [126, 127, 128, 129, 130, 131, 132]

  • N -acetylcysteine (Mucomyst)

  • S-2-(3-aminopropylamino) ethyl phosphorothioic acid (amifostine) [118]

  • Pentosan polysulfate sodium

Mesna binds to acrolein, the caustic metabolite of cyclophosphamide and ifosfamide, creating stable thioester compounds with no bladder toxicity. [133] Because it decreases the chemotherapeutic efficacy of cyclophosphamide, N-acetylcysteine is less desirable than mesna, which is generally not reported to decrease the efficacy of cyclophosphamide.

Mesna can be given either orally or intravenously, and its routine concurrent administration has been recommended in the treatment of patients receiving cyclophosphamide and ifosfamide chemotherapy. In patients receiving cyclophosphamide and mesna who develop hemorrhagic cystitis, discontinuation of mesna is recommended. Unfortunately, mesna is much more successful at preventing active bleeding than it is at treating it.

Discontinuation of cyclophosphamide is mandatory in patients with developing hemorrhagic cystitis, because hematuria can subside with this maneuver in most patients.

Even if hemorrhagic cystitis does not develop during the use of cyclophosphamide, the patient’s lifetime risk of developing bladder cancer is increased 9-fold after receiving the agent. Mesna administration may decrease this risk. The addition of dexamethasone with mesna may improve the results. [134]

Treatment with estrogen has been shown to control hemorrhagic cystitis in children, adolescents, and adults with hemorrhagic cystitis due to various causes, including cyclophosphamide chemotherapy. [123, 135, 136] Hyperbaric oxygen has also been, used with moderate success, in refractory hematuria due to cyclophosphamide chemotherapy. [137]

Studies in rats have shown the following agents to be effective for prevention and/or treatment of cyclophosphamide-induced hemorrhagic cystitis

  • Intravesical epinephrine [138]

  • Oral tadalafil [139]

  • Oral vitamin C and histidine [140]

  • Pentoxifylline [141]

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