Furosemide for prevention of cyclophosphamide‐associated sterile haemorrhagic cystitis in dogs receiving metronomic low‐dose oral cyclophosphamide

Abstract

Sterile haemorrhagic cystitis (SHC) is a known risk of cyclophosphamide treatment. Diuresis using furosemide is effective in canines when maximally tolerated dosed cyclophosphamide is administered. This retrospective study aimed to determine whether orally administered furosemide decreased the incidence of SHC. Secondary aims were to identify predisposing factors for SHC. One-hundred and fifteen dogs treated with metronomic cyclophosphamide were analysed retrospectively. Populations were not randomized. 25 dogs (21.7%) developed SHC. Furosemide administration significantly reduced the likelihood of SHC development (P = 0.010, where SHC was diagnosed in 30.3% of dogs administered cyclophosphamide without furosemide, and 10.2% of dogs administered cyclophosphamide with furosemide). Age, gender, breed, bodyweight, number of cyclophosphamide treatments, piroxicam use and previous or pre-existing disease were not found to be associated with SHC development. This study demonstrates furosemide is effective in the prevention of SHC and its use may be considered when implementing metronomic cyclophosphamide therapy.

Retrospective comparison of first‐line adjuvant anthracycline vs metronomic‐based chemotherapy protocols in the treatment of stage I and II canine splenic haemangiosarcoma

“…MC with cyclophosphamide was related to mild toxicity and SHC resolved with the use of supportive treatment. SHC was documented in a total of 31% of dogs in this study, which is similar to previous reports . However, this is likely biased by the study population and the shorter survival time.…”

“…However, this is likely biased by the study population and the shorter survival time. Diuretics were not used concurrently in any of the dogs receiving MC though they might be considered to reduce the likelihood of SHC in treated dogs, as reported in a recent study . Furthermore, monitoring for haematuria was not standardized between the different institutions, which may lead to under‐reporting of SHC …”

The addition of metronomic chemotherapy does not improve outcome for canine splenic haemangiosarcoma

“…Although none of the patients in our study received furosemide with MC, it has been suggested that furosemide administered with MC cyclophosphamide significantly reduces the risk of SHC (Setyo et al . ). MC appears to be safe and well tolerated, although its efficacy appears to be limited for splenic HSA.…”

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

“…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 …”