Intravesicular carboprost for the treatment of hemorrhagic cystitis after marrow transplantation

Objectives: To determine the minimal active dose and extent of activity of intravesicular carboprost for the treatment of hemorrhagic cystitis after marrow transplantation. Methods: Twenty-four adults with grade 3 or 4 hemorrhagic cystitis were treated. All but 2 had failed other local therapy. Treatment was initiated at a median of 32 days post-transplant. Eleven patients received carboprost intravesicularly at 0.2 mg/dL for 60 minutes every 6 hours, and the dose was escalated every 24 hours until a dose of 1.0 mg/dL was reached unless a response was achieved. Thirteen additional patients were treated at an initial dose of 0.8 mg/dL, with escalation to 1.0 mg/dL after four doses in the absence of a response. Results: Overall, 15 of the 24 patients responded. In the dose-escalation setting, 0.8 mg/dL was the minimal active dose. The total response rate was 62% with doses at or above 0.8 mg/dL and 18% at lower doses. All but one response occurred with 7 or fewer days of therapy, and 9 patients relapsed later. Four additional patients were salvaged following cystoscopy with clot evacuation with or without alum or formalin instillation. In all but 1 patient, bladder spasms developed during treatment with carboprost, but were not sufficiently severe to discontinue therapy. Conclusions: Intravesicular carboprost at 1.0 mg/dL every 6 hours for no more than 7 days should be considered or a randomized study for treatment of refractory hemorrhagic cystitis. Cystoscopic examination and evacuation of clots prior to therapy may be required to achieve the full benefit of this treatment.