According to the 2008 update of American Society of Clinical Oncology (ASCO) guidelines, mesna plus saline diuresis is recommended with cyclophosphamide to prevent hemorrhagic cystitis in the setting of bone marrow transplantation. There are also insufficient data to make a recommendation on a specific monitoring protocol for hemorrhagic cystitis in patients receiving mesna to ameliorate high-dose cyclophosphamide–associated urothelial toxicity. [1]
A 2020 comprehensive literature review included 14 studies (nine prospective and five retrospective) to evaluate the incidence of hemorrhagic cystitis (HC) in patients receiving cyclophosphamide with or without mesna. Several studies supported utilizing mesna to prevent cyclophosphamide-induced HC, whereas other studies either revealed no significant difference between the patients using mesna vs the control group or indicated mesna can increase the risk of HC (see table 1 for the summary of related studies). Additionally, a 2020 retrospective cohort study (N= 718) did not support the benefit of mesna in preventing HC. There was a significantly greater incidence of hemorrhagic cystitis (3.5% vs. 0.4%, p <0.004) as well as a significantly greater cumulative dose (mg) of cyclophosphamide therapy (3,103 ± 1,696 vs. 2,465 ± 1,528; p <0.001) in the mesna group versus those patients who were not given therapy with mesna. Overall, large differences among the published trials and various study designs as well as patient populations warrant the need for future quality prospective trials to reflect the benefit of mesna in preventing HC. [2]
A 2016 review article discussed the protective effect of mesna in cyclophosphamide- and ifosfamide-induced HC. One cohort study revealed there was no protective effect of mesna in patients who received cyclophosphamide for their rheumatic disease (1.53% of HC in mesna groups vs. 1.8% HC in the non-mesna group; p= 0.08). Moreover, studies have demonstrated that mesna has been linked to significant adverse events such as urothelial and mucosal changes. Overall, the authors concluded that although mesna is the most widely used agent that neutralizes the destructive metabolite, acrolein, its uroprotective benefit for HC prophylaxis can not be affirmed by evidence-based studies. [3]
An article providing a general overview on mesna recommends that the agent be first administered as an injection concurrently with cyclophosphamide or ifosfamide chemotherapy. If the physician deems that it is still necessary after the initial dosage, an oral form (400 mg tablet) is usually administered 2 to 6 hours following subsequent therapy. [4]
According to the Electronic Medicines Compendium (EMC), which provides prescribing information for medications licensed for use in the United Kingdom, mesna is given by intravenous injection over 15-30 minutes at 20% of the simultaneously administered oxazaphosphorine (i.e., cyclophosphamide or ifosfamide) IV bolus on a weight for weight basis (w/w). The same dose of mesna is repeated after 4 and 8 hours. The total dose of mesna is 60% (w/w) of the oxazaphosphorine dose. This is repeated on each occasion that the cytotoxic agents are used. If necessary, the dose of mesna can be increased to 40% of the oxazaphosphorine dose given four times at three-hourly intervals (0, 3, 6, and 9 hours; total dose= 160% [w/w] of the oxazaphosphorine dose). This larger dose is recommended in children, in patients whose urothelium may be damaged from previous treatment with oxazaphosphorine or pelvic irradiation, or in patients who are not adequately protected by the standard dose of mesna. When cyclophosphamide is used orally, the same dosage regimen of mesna applies as though cyclophosphamide were used as an IV bolus. See Table 3 for an example dosage schedule of mesna given with cyclophosphamide/ifosfamide. [5]
A published abstract describes one hospital’s protocol for mesna administration to prevent the development of cyclophosphamide-associated hemorrhagic cystitis in autologous transplant patients. Mesna IV is given at the same dose of cyclophosphamide in four equally divided doses at 15 minutes before, then 3, 6, and 8 hours after the administration of cyclophosphamide. Following a retrospective review evaluating the effectiveness of this dosing schedule with aggressive IV hydration in preventing the development of hemorrhagic cystitis (HC) in autologous stem cell transplant patients, the authors concluded these methods were effective. [6]