Pilot Study to Test the Efficacy and Safety of Recombinant Factor VIIa (rFVIIa, NovoSeven™) in the Treatment of Refractory Hemorrhagic Cystitis Following High Dose Chemotherapy.

Background: Hemorrhagic cystitis (HC) is a known complication of high-dose cyclophosphamide, which is part of the conditioning regimen for stem cell transplantation, and is associated with significant morbidity. Treatment of HC is frequently unsatisfactory, leading to prolonged hospitalization and utilization of health care resources. High-dose recombinant factor VIIa (rFVIIa) is used as a hemostatic agent in patients with hemophilia with inhibitors. As rFVIIa enhances the generation of thrombin on activated platelets and facilitates the formation of a stable fibrin plug that is resistant to premature lysis, we conducted a pilot study to assess its efficacy and safety in the treatment of HC.

Methods: Subjects between 18–65 years with severe HC that was judged unresponsive to (a) optimization of hemostatic parameters, and (b) a trial of at least 24-hours of continuous bladder irrigation using a standardized protocol were eligible. Consented subjects were administered 80 μg/kg of rFVIIa for the first dose, and 120 μg/kg every 3 hours for up to 2 additional doses if hematuria was persistent. Response was evaluated by monitoring urine color photographically and by measuring urine hemoglobin content, using spectrophotometer. Subjects were followed for 24 hours. Complete response was defined as complete clearing of the color of urine at any time point in the 24-hour study period, and partial response was defined as slowing of hematuria, as evidenced by lightening of the color of urine.

Results: Of the 7 subjects who participated in the study, 4 had a complete response, 2 had a partial response, and 1 had no response. The response duration was temporary, and all the subjects required the administration of the three doses of rFVIIa. No major adverse effects were encountered.

Conclusion: rFVIIa appears to be effective in temporarily abating bleeding in HC. Further trials should include multiple dosing and/or addition of antifibrinolytic agents for a more durable effect.