Risks and mitigation strategies to prevent etoposide infusion‐related reactions in children

Abstract

Etoposide is an antineoplastic agent widely used for treatment of many pediatric cancers. Etoposide has been associated with infusion‐related reactions. In this brief report, we compare etoposide infusion‐related reactions that occurred over a 10‐year period at two freestanding pediatric hospitals. Infusion reactions occurred in 1% of patients at two hospitals across the study period. Rates of 4.8%, 3.4%, and 7.9% were observed at Children's Mercy Hospital during 2018, 2019, and 2020, respectively, after the implementation of in‐line filters during etoposide infusions in late 2017. Of the 32 patients who experienced adverse reactions, 41% were rechallenged after the reaction and all were able to tolerate at least one future dose with either pre‐treatment or extending infusion duration. This work highlights the importance of a multicenter approach to investigating adverse drug reactions (ADRs) as variation in practice can provide key information about ADRs and potential risk factors.

Acute infusion-related reactions in pediatric patients receiving etoposide at a tertiary cancer center

“…Primary literature and package insert data suggest that non-anaphylactic IRRs can occur in 1.3%–27.1% of patients with one study treating pediatric patients with acute leukemia reporting IRRs in up to 33% of patients. 1–3,6 The rate of etoposide IRRs reported in this analysis (10%) is consistent with the package insert and previous literature. The results of this study do highlight the following findings: (1) Most reactions occurred in patients with classical Hodgkin's lymphoma, (2) higher rate of infusion was associated with an increased reaction rate, (3) an increased incidence of IRRs was observed at the end of the study period.…”

“…This drug is a key component of many pediatric chemotherapy regimens for both hematologic and solid tumors. 1,2 It is well documented in both the primary literature and package insert that patients receiving etoposide may experience anaphylaxis (0.7%-2%) or non-anaphylactic (1.3%-27.1%) infusion-related reactions (IRRs). [1][2][3] The cause of IRR to etoposide (majority of which are type I hypersensitivity reactions) is thought to be mainly due to the solvent polysorbate-80.…”

“…1,2 It is well documented in both the primary literature and package insert that patients receiving etoposide may experience anaphylaxis (0.7%-2%) or non-anaphylactic (1.3%-27.1%) infusion-related reactions (IRRs). [1][2][3] The cause of IRR to etoposide (majority of which are type I hypersensitivity reactions) is thought to be mainly due to the solvent polysorbate-80. 4 Etoposide phosphate is a water-soluble prodrug of etoposide that does not contain the solvent polysorbate-80.…”

Etoposide hypersensitivity reactions associated with in-line filter use: A retrospective cohort study at CHU de Québec-Université Laval

“…Recently, two pediatric studies have provided evidence of HSRs related to the use of ILFs during etoposide infusion, 20,21 yet, to the best of our knowledge, our study is the first to demonstrate a significant association in a predominantly adult cohort.…”

“…However, the fact that all the doses were administered over 2 h in the second hospital could have favored the lower HSR risk in the absence of filters. 21 With regard to the severity of the HSRs observed in this study, most were grade 2. Grade 3 HSRs were observed only in patients who received etoposide with ILF.…”