(046) Comparison of Hemorrhagic Cystitis Rates With and Without Prophylactic Mesna for Cyclophosphamide Cycles in Ewing Sarcoma Patients Receiving VAdriaC/IE

Poster Abstract: Cyclophosphamide and ifosfamide confer the risk of hemorrhagic cystitis (HC) due to the urotoxic metabolite acrolein. ASCO Clinical Practice Guidelines for the (Use of Chemotherapy and Radiotherapy Protectants) recommend administration of the detoxifying agent mesna with ifosfamide at all doses, but only with cyclophosphamide when administered at ≥50 mg/kg/dose for stem cell transplantation. Historically, VAdriaC/IE (vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide) for Ewing sarcoma, includes prophylactic mesna with both cyclophosphamide- and ifosfamide-containing cycles despite cyclophosphamide being dosed at 1200 mg/m2/dose. To align with the ASCO Guidelines, mesna was removed from the VAdriaC cycles at our institution. To the best of our knowledge, this is the first study to explore the incidence of HC without prophylactic mesna for Ewing sarcoma patients.

The primary objective was to compare the incidence of HC in patients who did versus those who did not receive prophylactic mesna with cyclophosphamide. The secondary objective was to quantify the cost-savings of this change.

A retrospective chart review was conducted to compare the rates of HC between the two patient groups in those who received at least one cycle of VAdriaC/IE between August 2017 and June 2023. A Pearson test was used to explore the differences in rates of HC. A Pearson or Wilcoxon test were used to explore potentially confounding factors on HC development such as pre-existing urinary problems, pelvic involvement of disease, maintenance of dose intensity, and cumulative dose of cyclophosphamide received.

Of the 34 patients included in this study, 22 received prophylactic mesna and 12 did not. The incidence of HC was zero in both groups and there were no differences in the rates of gross hematuria (8% vs 9%, p=0.941), irritative voiding (17% vs 9%, p=0.512), or urinary incontinence (0% vs 0%). There was no difference in the identified confounding variables. The results of the secondary objective were an estimated institutional pharmacy cost savings of $3,198 and potential infusion center revenue of $270,816 per year.

Removal of prophylactic mesna from cyclophosphamide-containing cycles in VAdriaC/IE did not increase the incidence of HC, hematuria, or irritative voiding in patients with Ewing sarcoma. There was improvement in patient convenience due to reduced infusion chair time and medication cost. There was also improvement in institutional revenue. This study provides preliminary evidence for the safety of removing mesna from VAdriaC during Ewing sarcoma treatment. Future studies should explore these findings in a larger population.

References (must also be included in final poster): 1. Hensley ML, Hagerty KL, Kewalramani T, et al. American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants. J Clin Oncol. 2009;27(1):127-145. doi:10.1200/JCO.2008.17.2627
2. Wexler LH, DeLaney TF, Tsokos M, et al. Ifosfamide and etoposide plus vincristine, doxorubicin, and cyclophosphamide for newly diagnosed Ewing's sarcoma family of tumors [published correction appears in Cancer 1997 Feb 15;79(4):867]. Cancer. 1996;78(4):901-911. doi:10.1002/(SICI)1097-0142(19960815)78:4 < 901::AID-CNCR30>3.0.CO;2-X
3. Miser JS, Kinsella TJ, Triche TJ, et al. Preliminary results of treatment of Ewing's sarcoma of bone in children and young adults: six months of intensive combined modality therapy without maintenance. J Clin Oncol. 1988;6(3):484-490. doi:10.1200/JCO.1988.6.3.484