Recommended Citation
Clennon A, Fisher M, Atienza S. Assessment of Fosaprepitant and Aprepitant Use as an Independent Risk Factor for Ifosfamide Neurotoxicity. Presented at Scientific Day; May 21, 2025; Park Ridge, IL.
Abstract
Background/Significance:
Ifosfamide neurotoxicity (IN) is estimated to occur in 10-30% of patients. The effect on incidence of IN when adding neurokinin 1 receptor antagonists (NK1RA) is conflicting in the literature. Fosaprepitant and aprepitant are NK-1RA agents with moderate CYP3A4 inhibition and ifosfamide is a strong CYP3A4 substrate. Theoretically, when combined, this can result in increased ifosfamide concentrations. Clinically, the medical community does not pre-emptively remove NK-1RA in ifosfamide regimens, although alternate antiemetics are available. Other cited risked factors for IN include hypoalbuminemia, poor kidney function, hyponatremia, poor liver function, and preexisting brain metastasis.
Purpose:
Assessing (fos)aprepitant use and other independent risk factors for IN will help guide the management of modifiable and non-modifiable factors, with the ultimate goal of decreasing IN rates.
Methods:
A retrospective, single center cohort study included patients between 18-89 years of age who received at least one cycle of an ifosfamide-containing regimen in Wisconsin region without (fos)aprepitant between Jan. 1, 2014-Dec. 1, 2016, or with (fos)aprepitant between Jan. 1, 2022-Dec. 1, 2024. Protected populations and those who had inadequate records were excluded. Risk factors collected included hypoalbuminemia, poor kidney function, hyponatremia, poor liver function, and preexisting brain metastasis. The primary outcome was to identify the incidence of IN with and without (fos)aprepitant use. A secondary outcome was assessed to identify the incidence of risk factors and impact on IN. Baseline characteristics and outcomes utilized descriptive statistics.
Results:
A total of 104 patients were included (n=52 (fos)aprepitant [A], n=52 in non-(fos)aprepitant [NA]). IN occurred in 25% (n=13) of patients who received fos(aprepitant) versus 9.6% (n=5) in those that did not (p=0.038). Risk factors for IN were more common in the NA group with hypoalbuminemia being the most common (56% A, 52% NA). Patients with 2 or more risk factors experienced the majority of IN within both groups (53.8% A, 80% NA).
Conclusion:
(Fos)aprepitant may be an independent risk factor for increasing IN. Rates of IN seen across the Advocate Health Midwest Region have risen in a clinically impactful manner, urging clinicians to consider primary prophylactic approaches to reduce incidence such as (fos)aprepitant-free antiemetics, albumin and thiamine supplementation, and methylene blue.
Presentation Notes
Presented at Scientific Day; May 21, 2025; Park Ridge, IL.
Full Text of Presentation
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Document Type
Poster
Assessment of Fosaprepitant and Aprepitant Use as an Independent Risk Factor for Ifosfamide Neurotoxicity
Background/Significance:
Ifosfamide neurotoxicity (IN) is estimated to occur in 10-30% of patients. The effect on incidence of IN when adding neurokinin 1 receptor antagonists (NK1RA) is conflicting in the literature. Fosaprepitant and aprepitant are NK-1RA agents with moderate CYP3A4 inhibition and ifosfamide is a strong CYP3A4 substrate. Theoretically, when combined, this can result in increased ifosfamide concentrations. Clinically, the medical community does not pre-emptively remove NK-1RA in ifosfamide regimens, although alternate antiemetics are available. Other cited risked factors for IN include hypoalbuminemia, poor kidney function, hyponatremia, poor liver function, and preexisting brain metastasis.
Purpose:
Assessing (fos)aprepitant use and other independent risk factors for IN will help guide the management of modifiable and non-modifiable factors, with the ultimate goal of decreasing IN rates.
Methods:
A retrospective, single center cohort study included patients between 18-89 years of age who received at least one cycle of an ifosfamide-containing regimen in Wisconsin region without (fos)aprepitant between Jan. 1, 2014-Dec. 1, 2016, or with (fos)aprepitant between Jan. 1, 2022-Dec. 1, 2024. Protected populations and those who had inadequate records were excluded. Risk factors collected included hypoalbuminemia, poor kidney function, hyponatremia, poor liver function, and preexisting brain metastasis. The primary outcome was to identify the incidence of IN with and without (fos)aprepitant use. A secondary outcome was assessed to identify the incidence of risk factors and impact on IN. Baseline characteristics and outcomes utilized descriptive statistics.
Results:
A total of 104 patients were included (n=52 (fos)aprepitant [A], n=52 in non-(fos)aprepitant [NA]). IN occurred in 25% (n=13) of patients who received fos(aprepitant) versus 9.6% (n=5) in those that did not (p=0.038). Risk factors for IN were more common in the NA group with hypoalbuminemia being the most common (56% A, 52% NA). Patients with 2 or more risk factors experienced the majority of IN within both groups (53.8% A, 80% NA).
Conclusion:
(Fos)aprepitant may be an independent risk factor for increasing IN. Rates of IN seen across the Advocate Health Midwest Region have risen in a clinically impactful manner, urging clinicians to consider primary prophylactic approaches to reduce incidence such as (fos)aprepitant-free antiemetics, albumin and thiamine supplementation, and methylene blue.
Affiliations
Aurora St. Luke's Medical Center