References

Mosteller RD Simplified calculation of body-surface area. N Engl J Med. 1987; 317:(17) https://doi.org/10.1056/NEJM198710223171717

Ntatsaki E, Carruthers D, Chakravarty K BSR and BHPR guideline for the management of adults with ANCA-associated vasculitis. Rheumatology (Oxford). 2014; 53:(12)2306-2309 https://doi.org/10.1093/rheumatology/ket445

Calculation Skills

Dosing of mesna to avoid urothelial toxicity from cyclophosphamide infusion

02 August 2022
Calculation Skills
02 August 2022
Volume 4 · Issue 8

Cyclophosphamide is an alkylating agent used as chemotherapy to treat a range of conditions, most notably certain types of cancer. It has useful immunosuppressive effects but is also predictably quite toxic.

One of the metabolites of cyclophosphamide is a toxic aldehyde called acrolein. Acrolein collects in the bladder following administration of cyclophosphamide and is an extreme irritant, leading to the development of hemorrhagic cystitis and potentially bladder cancer. In order to mitigate the damage to the bladder from acrolein accumulation, cyclophosphamide is usually co-administered with 2-mercaptoethanesulphonic acid, more easily remembered as mesna. Following administration, mesna concentrates in the bladder and forms complexes with acrolein, which renders it non-toxic. Given that this is a direct physical interaction between the acrolein and mesna, repeated doses are necessary to ensure there is mesna available in the bladder until all the metabolites have been excreted.

The following case considers the treatment of a vasculitis patient for whom an intermittent dose of fortnightly cyclophosphamide is required.

The patient has serum creatinine of 120 micromolar and a reduced dose based on renal impairment is not considered to be necessary. Liver function is normal.

QUESTION 1

Given that they weigh 7 stone 13lb and are 5′4′′ tall, use the Mosteller (1987) formula (Figure 1) for body surface area to calculate the dose determining body surface area in m2.

Figure 1. BSA Calculation

QUESTION 2

Using your answer to question 1, calculate the cyclophosphamide dose required. The clinicians would like to use the lower end of the summary of product characteristics (2014) recommended dose of cyclophosphamide for autoimmune disorders; 500mg/m2 every fortnight initially.

To reduce endothelial toxicity, the recommendation from the British Society of Rheumatology (Ntatsaki et al, 2014) is that the administered dose of cyclophosphamide reflects the dose of mesna required, though the proportion does vary depending on the route. For intravenous mesna, it is recommended that each dose, in mg, is 20% of the cyclophosphamide dose, also in mg. The doses of mesna are given with the cyclophosphamide infusion and repeated 2 and 6 hours after the cyclophosphamide too, to enable continued scavenging of the acrolein as it is produced and collects in the kidney.

QUESTION 3

How much mesna is required for each dose for this patient?