Etoposide and etoposide phosphate hypersensitivity in children: Incidence, risk factors, and prevention strategies

Winifred M Stockton , Theresa Nguyen , Lishi Zhang and Thomas C Dowling.

Corresponding author:
Winifred M Stockton, Children’s Hospital of Orange County, 1201 W La Veta Ave, Orange, CA 92868-3874, USA. Email: wstockton@choc.org

Introduction: Etoposide is critical in treating pediatric cancers, although hypersensitivity can be severe and treatmentlimiting. Reported rates of hypersensitivity range from 2% to 51%. Hypersensitivity data for etoposide phosphate, a newer product, are lacking. The primary objective of this study was to assess etoposide and etoposide phosphate hypersensitivity incidence. Secondary objectives included evaluation of potential risk factors for hypersensitivity and strategies to prevent recurrence. 

Methods: This retrospective cohort study evaluated pediatric patients who received initial etoposide phosphate or etoposide dose between August 2012 and July 2017. The primary outcome was documentation of hypersensitivity within four months of initial dose. Potential risk factors evaluated included age, allergies, dose, infusion rate, infusion concentration, and premedication. 

Results: Of 246 patients, hypersensitivity reactions occurred in five of 54 patients (9.3%) who received etoposide phosphate and 52 of 192 patients (27.1%) who received etoposide (p ¼ 0.0061). For etoposide, the mean initial infusion rate was 64.6 40.9 mg/m2/h for patients with hypersensitivity and 49.5 33.4 mg/m2 /h without hypersensitivity (p ¼ 0.0886). Etoposide phosphate rate was not associated with hypersensitivity. Recurrent hypersensitivity occurred in one of nine patients (11.1%) who received etoposide desensitization and one of 38 patients (2.6%) who changed formulation to etoposide phosphate. 

Conclusions: Etoposide was associated with more hypersensitivity than etoposide phosphate in pediatric patients. Etoposide hypersensitivity was associated with higher infusion rates, but not etoposide phosphate. Differences in hypersensitivity incidence and infusion rate influence indicate a formulation-effect. Etoposide hypersensitivity recurrence may be prevented by changing to etoposide phosphate formulation. During etoposide phosphate shortages, etoposide desensitization may prevent recurrent hypersensitivity.

J Oncol Pharm Practice 2020, Vol. 26(2) 397–405