Background To assess bladder toxicity of Cyclophosphamide (CYC) treatment and preventive effect of 2-mercaptoethane sulfonate (Mesna) in systemic autoimmune disorders.
Methods Six hundred fifty-six patients (F/M:479/177) with various systemic autoimmune disease who were treated with CYC at least 3 months were included to this analysis. The route of CYC administration, cumulative dosage and duration as well as mesna usage were evaluated. Relationship between hemorrhagic cystitis and six variables including CYC dosage route of administration, disease and mesna usage were assessed by survival analysis.
Results We identified 8/656 (1.2%) patients with hemorrhagic cystitis and 2/260 (0.76%) patients with bladder cancer. The median time for diagnosis to hemorrhagic cystitis was 4 (range 3-12) months and bladder cancer was 8 (6 and 10.9) years. Two hundred fifty-one (38%) patients during IV CYC administration had received mesna. The incidence of hemorrhagic cystitis was not different between patients with and without using mesna [2/251 (0.8%) vs. 6/405 (1.4%) respectively, HR:1.04, CI 0.2-5.2, p=0.9]. Hemorrhagic cystitis was found higher in Scleroderma (SSc) patients compared to other autoimmune disease [SSc: 4/215 (1.86%), SLE: 2/227 (0.88%) and vasculitis: 2/186 (1.07%), HR: 6.4, p=0.01] and the mean CYC dose was not different between the groups(p>0.05).
The mean (±SEM) CYC dose was 13.1±0.52 (range 1.5-144) g, duration of CYC treatment was 15.5±0.47 (range 3-102) months and follow-up time after CYC treatment was 59.4±2.0 (range 3-365) months. Cumulative CYC dose was higher in patients with hemorrhagic cystitis without significance (38.9±42.6 vs. 12.7±11.9 gram respectively, p=0.058).
The mean cumulative CYC dose was 112±5.6 g and duration of CYC treatment was 87±21.2 months in patients with bladder cancer.
The mean CYC dose was significantly higher for (ever-oral po or IV+po) versus IV only routes (10.3±5.6 vs. 32.8±28.5 gram respectively, p<0.001). In addition hemorrhagic cystitis incidence was found higher in ever-oral than IV only routes groups [4/80 (5%) vs. 4/576 (0.7%) respectively, HR:3.9, CI:0.9-15.9, p=0.056].
Conclusions Bladder toxicity is associated with cumulative CYC dose and its oral administration and could be higher in patients with SSc. However, no preventive effect of mesna on hemorrhagic cystitis was shown.
Disclosure of Interest None Declared