Mesna and furosemide for prevention of cyclophosphamide‐induced sterile haemorrhagic cystitis in dogs – a retrospective study

Abstract

Sterile haemorrhagic cystitis (SHC) is a possible side effect of cyclophosphamide which can severely impact quality of life. Mesna and diuresis are effective in human medicine to prevent SHC. The aim of the present study was to compare the efficacy of mesna versus diuresis with furosemide in preventing SHC in dogs treated with cyclophosphamide within a multidrug chemotherapy induction protocol for malignant lymphoma. Medical records of dogs treated at the Clinic of Small Animal Medicine, Munich, between 1997 and 2009 were analysed retrospectively. Of the 131 dogs included, 33 received no prophylaxis (group 1), 43 received mesna (group 2), and 55 received furosemide (group 3). Age, gender, breed, bodyweight, body surface area, dose and application method of cyclophosphamide, and the method of SHC prophylaxis were compared between dogs with and without SHC. Six dogs (4.6 per cent) developed SHC. The incidence of SHC in groups 1, 2 and 3 was 4/33 (12.1 per cent), 1/43 (2.3 per cent), and 1/55 (1.8 per cent), respectively. Dogs receiving either mesna or furosemide were significantly less likely to develop SHC (P=0.03). Otherwise no significant differences were found. In conclusion, this study demonstrates the efficacy and the medical indication of mesna and furosemide for prevention of cyclophosphamide-induced SHC.

Glutathione‐S‐transferase‐theta genotypes and the risk of cyclophosphamide toxicity in dogs

“…The overall incidence of SHC in the University of Wisconsin-Madison dogs enrolled in this study was 8.9%. This is comparable to other studies, in which SHC was found in 3.8% to 9.0% of pulsetreated dogs, 15,21,25,26 and in 3.6% to 32% of metronomic CP-treated dogs 13,16,18,27 Metronomic CP was a significant risk factor for SHC in our study. Cumulative CP doses were nearly 3-fold higher with metronomic compared to pulse protocols, and higher cumulative doses are a risk factor for SHC.…”

“…Cumulative CP doses were nearly 3‐fold higher with metronomic compared to pulse protocols, and higher cumulative doses are a risk factor for SHC . The metronomic CP protocol in our population did not include furosemide, which may have increased SHC risk . However, SHC can develop after even a single dose of intravenous CP or in the presence of furosemide, so other factors are likely involved.…”

“…For each dog, the following data were recorded: signalment, tumour type, CP dosing and frequency, route of administration, cumulative CP dose, and clinical outcomes of SHC, myelosuppression or GI toxicity. Concurrent drug administration was recorded, including NSAIDs and furosemide or prednisone …”

“…Concurrent drug administration was recorded, including NSAIDs 13 and furosemide or prednisone. [14][15][16][17] The presence of SHC was defined as newly observed haematuria with pollakiuria or stranguria and a negative urine culture, at any time during CP treatment. 18 BM and GI toxicities were determined from the history, physical examination and CBC during the 7 to 10 days after intermittent CP administration.…”

Reducing the side effects of cyclophosphamide chemotherapy in dogs

“…The paper by Laberke and others (2014), summarised on p 250 of this issue of Veterinary Record , should be of interest to those in small animal practice, in highlighting the risk of haemorrhagic cystitis in dogs receiving cyclophosphamide and in demonstrating the efficacy of medical prophylaxis of this serious adverse effect when high-dose cyclophosphamide protocols (for example, CHOP) are used. It shows that in this group of dogs, furosemide diuresis was as effective as the more expensive and complicated mesna option.…”