Aim The anti-cancer agents ifosfamide and cyclophosphamide are used commonly in the treatment of childhood cancers, across many regimens. The high doses used can sometimes precipitate haemorrhagic cystitis which is a dose limiting toxicity caused by the metabolic breakdown products acrolein and 4-hydroxyifosfamide. Worldwide, mesna (sodium-2-mercatpoethane suplhonate) combined with hydration is used to prevent, and treat, accumulation of these metabolites causing haemorrhagic cystitis.^{1 2}

The fluids and mesna are continued for 12 to 24 hours after the chemotherapy stops meaning patients have a prolonged inpatient stay to provide hydration and mesna to help excrete these metabolites from the body.

To shorten the length of time in hospital it may be appropriate to stop intravenous mesna and fluids early in some children and allow patients to drink and have mesna by mouth at home. For this to occur the patient needs to be able to drink the required volume of fluid that would have been given intravenously and can take oral mesna, either be dissolving it or by swallowing a tablet.

Method If a child is eligible, 40% of the 24-hour dose of ifosfamide or cyclophosphamide is given as an intravenous bolus pre AND post the administration of the final day of either cyclophosphamide or ifosfamide. The same dose will then be given in oral form and taken 2 hours and 6 hours after the end of the chemotherapy infusion. Mesna tablets come in 400 mg and 600 mg strengths. They are scored, which may help with dosing and can be dissolved in 100 ml of water which takes about 20 minutes. They can also be crushed if required. Any dissolved Mesna should be taken immediately; the drug can be given via an NG tube. Should the child be sick in the hour following administration, the dose should be repeated.^{1 2}

Results So far three patients have taken part in this new regimen, both were successfully discharged home earlier than normal saving 18 hours inpatient time each. There were no adverse effects noted. Although it is recognised that the volume of water needing to be consumed is large and may be a limitation for some patients.

Conclusion As this new regimen is used more frequently the length of stay for patients being prescribed cyclophosphamide or ifosfamide will be reduced significantly. This will allow for more time at home, and in the longer term this may also reduce inpatient bed pressure on the ward.

References

1. Haemorrhagic Cystitis: A challenge to the urologist Indian J Urol. 2010;26:159–166 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938536/

2. University College London (UCL) Guidelines for the Administration of Mesna with Ifosfamide and Cyclophosphamide 2018.