(115) Evaluation of the Incidence of Ifosfamide-Induced Neurotoxicity with Concomitant Fosaprepitant in Sarcoma Patients

Poster Abstract:

Background: Ifosfamide is an alkylating agent used in the treatment of various malignancies including sarcomas. Ifosfamide-induced neurotoxicity occurs in up to 30% of patients. Fosaprepitant is an antiemetic agent often used as a pre-medication for ifosfamide infusion and may be associated with an increased risk of ifosfamide-induced neurotoxicity through CYP3A4 inhibition. Previous studies have found inconclusive results regarding this association.

Objectives: The primary objective was to determine the incidence of ifosfamide-induced neurotoxicity with concomitant fosaprepitant vs. without fosaprepitant. Secondary objectives include evaluating the incidence of other ifosfamide-induced toxicities (nephrotoxicity, hepatotoxicity, and cystitis), factors associated with ifosfamide-induced neurotoxicity, and ifosfamide-induced neurotoxicity management strategies.

Methods: A single-center, retrospective chart review of adult patients who received at least one dose of ifosfamide for the treatment of sarcoma between June 16, 2022, and June 15, 2023, was conducted. Patients who received ifosfamide for a non-sarcoma diagnosis were excluded. Variables assessed include baseline characteristics, diagnosis, ifosfamide dose, onset of neurotoxicity, neurotoxicity signs/symptoms, neurotoxicity treatment, acute kidney injury (AKI), hepatotoxicity, and cystitis.

Results: This study included 28 sarcoma patients who received a total of 68 cycles of ifosfamide-based chemotherapy. Of these patients, 18 received concomitant fosaprepitant, for a total of 42 chemotherapy cycles. Neurotoxicity was identified in 13 patients (46.4%) of which 7 (53.8%) received fosaprepitant. Neurotoxicity occurred in 26 patient cycles (38.2%), of which 14 (53.8%) included fosaprepitant. AKI (n=6; 8.8%), hepatotoxicity (n=1; 1.5%), and cystitis (n=1; 1.5%) were also identified during chemotherapy cycles. The majority of cycles with neurotoxicity had an intervention (n=16; 61.5%), with the ifosfamide dose held in n=15 (57.7%). Mean baseline albumin was lower in patients with neurotoxicity vs. patients without neurotoxicity, 3.28 g/dL vs. 3.94 g/dL, respectively.

Conclusion: A high rate of neurotoxicity was identified in sarcoma patients receiving ifosfamide-based chemotherapy regimens. No increase in incidence of neurotoxicity with concomitant ifosfamide and fosaprepitant was found. Low albumin was identified as a potential risk factor for ifosfamide-induced neurotoxicity, which correlates with previous studies. While there may be a drug-drug interaction between ifosfamide and fosaprepitant, this study did not identify a clinically significant interaction.

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