Cetuximab is an anti-epidermal growth factor receptor antibody used for the treatment of metastatic colorectal cancer and head and neck cancer. Hypersensitivity reactions (HSRs) are associated with cetuximab use. The aim of the study was to evaluate the utility of anti-cetuximab immunoglobulin E (IgE) detection in order to identify patients at risk of HSR to cetuximab. We included patients ready to receive a first cetuximab infusion in a prospective cohort carried out at nine French centres. Pretreatment anti-cetuximab IgE levels were measured. We compared the proportion of severe HSRs in the low anti-cetuximab IgE levels (≤29 IgE arbitrary units) subgroup with that in a historical cohort of 213 patients extracted from a previous study. Of the 301 assessable patients (mean age: 60.9 ± 9.3 years, head-and-neck cancer: 77%), 66 patients (22%) had high anti-cetuximab IgE levels, and 247 patients received cetuximab (including 38 with high anti-cetuximab levels). Severe HSRs occurred in eight patients (five grade 3 and three grade 4). The proportion of severe HSRs was lower in the low anti-cetuximab IgE levels subgroup vs. the historical cohort (3/209 [1.4%] vs. 11/213 [5.2%], odds ratio, 0.27, 95% confidence interval, 0.07-0.97), and higher in high vs. low anti-cetuximab IgE levels subgroup (5/38 [13.2%] vs. 3/209 [1.4%]; odds ratio, 10.4, 95% confidence interval, 2.4-45.6). Patients with severe HSRs had higher anti-cetuximab IgE levels than patients without reaction (median, 45 vs. 2 IgE arbitrary units, P = 0.006). Detection of pretreatment anti-cetuximab IgE is feasible and helpful to identify patients at risk of severe cetuximab-induced HSRs.
Lledo G, Huguet F, Chibaudel B, Di Fiore F, Mineur L, et al.
European journal of cancer (Oxford, England : 1990) •
To determine efficacy and toxicity of radiation therapy combined with oxaliplatin, 5-fluorouracil, and folinic acid (FOLFOX) and cetuximab in patients with locally advanced oesophageal cancer. Patients with stage III oesophageal or gastro-oesophageal junction cancer were enrolled in a Simon's two-stage phase II study. Patients received FOLFOX and weekly cetuximab on week 1-10 with concurrent radiotherapy (50.4 Gy in 30 fractions) on week 5-10. Primary end-point was clinical overall response rate (ORR). An ORR rate of more than 50% was expected. Among the 79 included patients, clinical ORR was 77% with 40% complete responses. Median overall survival and progression-free survival were 21.6 and 11.3 months, respectively. The most common grade III-IV toxicities observed during experimental chemoimmunotherapy followed by chemoradiation included neutropenia (28%), oesophagitis (12%), rash (11%), and allergy (9%). There was one treatment-related death due to oesophagitis with gastrointestinal bleeding. Cetuximab-FOLFOX regimen combined with radiotherapy demonstrated its efficacy and was well tolerated. Unfortunately, these results were not confirmed in two recent phase III studies.
The Euonymus europaeus agglutinin (EEA) is an endothelial marker in mammalia. In canine tissues, 4 types of endothelial cells (general, nervous, arterial, hepatic) were identified by the presence of the EEA receptor and by its sensitivity to neuraminidase enhancement. In adult dogs, EEA binding saccharides had endothelial or epithelial distributions and reactivities similar to those described for human tissues. Different EEA reactivities were observed between fetal, neonatal and adult canine tissues mainly at the arterial level. These findings suggest that the development of the binding sites is not identical in dog and man. Related lectins and monoclonal antibodies were used to characterize the EEA binding site, and the probable structure of the EEA binding saccharide in endothelial cells appeared to be alpha Gal (1,3) beta Gal (1,4) GlcNAc.
