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

Oseltamivir combined with HIV drugs lopinavir and ritonavir the medications improved conditions in patients with severe 2019-nCoV infections

A combination of flu and HIV medications may be able to treat severe cases of 2019-nCoV, the new coronavirus that has emerged in China, according to doctors in Thailand who have been caring for infected patients. The team’s approach, which used large doses of the flu drug Oseltamivir combined with HIV drugs lopinavir and ritonavir, improved the conditions of several patients at the Rajavithi Hospital in Bangkok.

“This is not the cure, but the patient’s condition has vastly improved,” Rajavithi Hospital’s Kriangsak Atipornwanich says of one 70-year-old Chinese woman from Wuhan, according to Reuters. “From testing positive for 10 days under our care, after applying this combination of medicine the test result became negative within 48 hours.”

Thailand has so far recorded 19 cases of coronavirus, Reuters reports, making it the country with the greatest number of infections in Southeast Asia. Eight patients have recovered, while the rest are still undergoing treatment. Officials say that the country’s health ministry would meet today (February 3) to discuss the new treatment for severe cases. “We still have to do more study to determine that this can be a standard treatment,” Atipornwanich tells reporters.

Other countries have also showed interest in using HIV drugs against the new coronavirus. China’s National Health Commission recently began recommending lopinavir and ritonavir (sold together by Illinois-based pharma AbbVie as Kaletra), according to Fierce Pharma. AbbVie has pledged to donate about $1.5 million worth of Kaletra for the effort.

A randomized controlled clinical trial is now underway in China to test the anti-HIV drugs’ efficacy, according to a study published last week (January 24) in The Lancet. Scientists in Hong Kong will also likely test these drugs in patients alongside immune system–boosting medications, Hong Kong University microbiologist Yuen Kwok-Yung tells Science.

Other treatments being considered by national governments and pharma companies include Gilead Sciences’s remdesivir, a drug that was designed to treat Ebola but failed efficacy tests. “Gilead is working closely with global health authorities to respond to the novel coronavirus (2019-nCoV) outbreak through the appropriate experimental use of our investigational compound remdesivir,” the company’s Chief Medical Officer Merdad Parsey says in a statement.

Massachusetts-based Moderna Therapeutics, meanwhile, is collaborating with the US National Institute of Allergy and Infectious Diseases to develop an mRNA vaccine, Fierce Pharma reports.

Catherine Offord is an associate editor at The Scientist. Email her at cofford@the-scientist.com.