Cyclophosphamide Essay

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Cyclophosphamide is an alkylating agent used in the treatment of lymphoma, carcinomas and sarcomas in dogs. It is increasingly being used in ‘metronomic’ chemotherapy protocols.[1] Cyclophosphamide is a prodrug that requires oxidation in the liver to form the active metabolites which are in turn are converted to phosphoramide mustard and acrolein.[2] Phosphoramide mustard causes DNA damage and acrolein has inflammatory effects. Like many chemotherapy agents, cyclophosphamide may cause myelosuppression, gastrointestinal upset and alopecia; however, unlike most chemotherapy agents, it also carries the risk of sterile haemorrhagic cystitis (SHC). This leads to haemorrhage and fibrosis of the bladder epithelium.[3, 4] The mechanism with which cyclophosphamide induces SHC is unknown. Though acrolein is thought to play a role in cyclophosphamide-associated SHC, cyclophosphamide has also been shown to initiate an early wave of apoptosis when caspase-3/7 is cleaved by caspase-1.[5] This apoptosis occurs in the urothelium and the damage caused may induce SHC. SHC is characterised by lower urinary tract signs of haematuria, stranguria and pollakiuria in the absence of urinary tract infection (UTI).[6] It has been shown to develop during long-term metronomic …show more content…

There is good evidence which supports the ability of furosemide and MESNA in preventing cyclophosphamide-induced SHC.[15] Currently, the recognised standard of practice for administration of cyclophosphamide is to give a single oral or IV dose of cyclophosphamide with concurrent furosemide treatment.[1,

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