Reduced incidence of infusion‐related reactions in metastatic colorectal cancer during treatment with cetuximab plus irinotecan with combined corticosteroid and antihistamine premedication

Abstract

BACKGROUND:The multinational MABEL study of 1147 patients with metastatic colorectal cancer (mCRC) who had recently failed an irinotecan-containing regimen confirmed in a community practice setting the efficacy and safety of cetuximab combined with irinotecan. METHODS: This report describes a post hoc analysis of the influence of prophylactic premedication on the incidence of infusion-related reactions (IRRs) in the MABEL study. The analysis was focused on the subpopulation of patients premedicated with antihistamines either with (n ¼ 700) or without (n ¼ 422) corticosteroids. Stepwise Cox regression modeling was used to examine the explanatory value of the type of premedication on progression-free survival (PFS) and overall survival (OS) times. RESULTS: The incidence of IRRs was lower in the group of patients who received antihistamine plus corticosteroid (9.6%) compared with those who received antihistamine alone (25.6%). A similar trend was seen for grade 3 or 4 IRRs (1.0% vs 4.7%, respectively). The 12-week PFS rates (61% vs 60%), median PFS (16.1 vs 13.1 weeks) and OS (9.2 vs 9.0 months) times for patients who received, respectively, antihistamines with and without corticosteroids were similar. Cox regression modeling did not identify any impact of type of premedication used (antihistamine with or without corticosteroids) on the efficacy of treatment in relation to PFS or OS. CONCLUSIONS: Prophylactically premedicating mCRC patients with both antihistamine and a corticosteroid appeared to reduce the frequency of cetuximab-associated IRRs. Given that this was a post hoc analysis, caution must be exercised in the interpretation of these data, which require formal confirmation in a randomized study.

Pre-medications for cetuximab induced infusion reactions – Commentary

“…Their results suggest the addition of dexamethasone, albuterol and famotidine to diphenhydramine prior to cetuximab reduces the incidence of overall as well as high-grade HSR. This finding is in agreement with a retrospective analysis of the MABEL trial, which indicated that dexamethasone as a premedication reduced the rate of HSR [2]. However, the data presented by Touma and colleagues demonstrate no clear beneficial effect of corticosteroids when added to diphenhydramine, with 22.6% and 12.9% of patients receiving the combination experiencing an HSR of any grade or high-grade, respectively.…”

Targeted agents: review of toxicity in the elderly metastatic colorectal cancer patients

“…It is very common, with up to 88% of patients experiencing a rash, but with most events being grade 1 and 2 [20]. Severe infusion reactions may occur in 1.4% to 4.5% [13,15,21], but it seems that they can be reduced by giving premedication with antihistamines and corticosteroids [22]. Hypomagnesaemia is a common side effect of CETUX that may occur in half of the patients receiving the treatment, with grade 3 and 4 events in as many as 25% of patients [23,24].…”

Management of occupational Hymenoptera allergy

“…We recommend application of a potent topical corticosteroid to the sting site before the area is cooled with wet dressings or cool packs. The beneficial effects of antihistamines and/or systemic corticosteroids are well documented, for example for the prevention of late-phase drug reactions [15] and also of LLR during VIT [16]. Even if there are no controlled studies, it appears justified to recommend these drugs for the self-medication of LLRs.…”