Although Dr. Alexander Dimitrios Colevas of the Internal Medicine, Stanford University School of Medicine, Stanford, CA, US and colleagues were unable to demonstrate an association between dexamethasone dose and rate of hypersensitivity reactions in a retrospective evaluation of data from 3,181 patients, their data show a higher rate of hypersensitivity reactions in female patients and patients with gynaecologic cancers. Routine use of lower doses, such as a single 10 mg dose of dexamethasone, as premedication for prescribing taxanes to prevent hypersensitivity reactions is preferable according to an article they published on 6 August 2021 in the Journal of Clinical Oncology.
The authors wrote in the study background that despite the widespread use of paclitaxel and docetaxel for different cancer types and their well-known association with hypersensitivity reactions, there is still significant variation in the prescribing practices of steroids for premedication. Premedication almost always includes dexamethasone, which can be associated with multiple side effects if taken for extended periods of time.
The dexamethasone regimen used in early phase I clinical studies is the same as that currently recommended. The authors wrote that despite well-known association with hypersensitivity reactions and significant clinical variation in dexamethasone premedication, there has not been research into optimising the dose of dexamethasone. Improvised lower dose regimens are routinely used, and the recommended dosage may be inefficient, leading to increased risk of either hypersensitivity reactions or side effects of corticosteroids.
The study team reviewed the pattern of premedication in patients who received paclitaxel or docetaxel at Stanford Cancer Institute between January 2010 and June 2020 to determine whether an association between dexamethasone premedication regimens and hypersensitivity reactions could be found. They used an electronic query of the electronic medical records followed-up with a manual review of patients data. Variables considered included steroid dose and route, dose and type of taxane, clinical cancer group, sex, and race.
The study researchers identified 5,217 patients who received paclitaxel or docetaxel, but 3,181 patients met criteria for the analysis. There were 264 hypersensitivity reactions (8.3%). In adjusted multivariate analysis, there was no correlation of hypersensitivity reactions rate or severity among any of the variables evaluated except patients in the gynaecology oncology clinic, who had an increased risk (hazard ratio [HR] 1.34) of hypersensitivity reactions overall and high grade hypersensitivity reactions (HR 2.34), as well female patients, who had a higher rate of hypersensitivity reactions overall (HR 1.26), but not high grade hypersensitivity reactions.
The authors commented that they did not find evidence of differences in dexamethasone dose or route of dexamethasone administration in terms of rates of hypersensitivity reactions. They concluded that in their adjusted multivariate analysis, patients who received high dose dexamethasone did not have significantly different rates of hypersensitivity reactions than those who received low dose dexamethasone. Gynaecologic cancer and female sex were significantly associated with higher rates of hypersensitivity reactions.
Many patients are receiving 40 mg of dexamethasone once weekly over the course of several months. The side effects of such dexamethasone exposure range from mild or moderate (e.g. dermatitis, cataracts, Cushing syndrome, impaired glucose metabolism, and gastric ulcers) to severe and life-threatening (e.g. masked septicaemia, arrhythmias, and avascular necrosis). Dexamethasone 40 mg before taxane administration does not protect from hypersensitivity reactions beyond 10 mg. Given the side effects of long term high dose steroids, a single low dose of 10 mg of dexamethasone can be used to minimise both hypersensitivity reactions and steroid side effects in most patients.
Reference
Lansinger OM, Biedermann S, He Z, et al. Do Steroids Matter? A Retrospective Review of Premedication for Taxane Chemotherapy and Hypersensitivity Reactions. JCO; Published online 6 August 2021. DOI: 10.1200/JCO.21.01200