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Oral Oncol. 2016 Dec;63:38-43. doi: 10.1016/j.oraloncology.2016.10.006. Epub 2016 Nov 12.

Epidermal growth factor receptor (EGFR) pathway polymorphisms as predictive markers of cetuximab toxicity in locally advanced head and neck squamous cell carcinoma (HNSCC) in a Spanish population.

Author information

1
Medical Oncology Service, University Hospital of Salamanca-IBSAL, Salamanca, Spain; Biomedical Research Institute of Salamanca (IBSAL), SACYL-University of Salamanca-CSIC, Salamanca, Spain; Molecular Medicine Unit-IBSAL, Department of Medicine, University of Salamanca, Spain; Institute of Molecular and Cellular Biology of Cancer (IBMCC), University of Salamanca-CSIC, Salamanca, Spain.
2
Medical Oncology Service, University Hospital of Salamanca-IBSAL, Salamanca, Spain; Biomedical Research Institute of Salamanca (IBSAL), SACYL-University of Salamanca-CSIC, Salamanca, Spain.
3
Medical Oncology Department, Institut Català d'Oncologia L'Hospitalet de Llobregat, Barcelona, Spain.
4
Medical Oncology Service, Hospital Universitario Politécnico La Fe, Valencia, Spain.
5
Division of Medical Oncology, Oncology Department, Hospital Costa del Sol, Marbella, Spain.
6
Radiation Oncology Department, Institut Català d'Oncologia L'Hospitalet, Barcelona, Spain.
7
Biomedical Research Institute of Salamanca (IBSAL), SACYL-University of Salamanca-CSIC, Salamanca, Spain; Molecular Medicine Unit-IBSAL, Department of Medicine, University of Salamanca, Spain; Institute of Molecular and Cellular Biology of Cancer (IBMCC), University of Salamanca-CSIC, Salamanca, Spain. Electronic address: gonzalez@usal.es.
8
Medical Oncology Service, University Hospital of Salamanca-IBSAL, Salamanca, Spain; Biomedical Research Institute of Salamanca (IBSAL), SACYL-University of Salamanca-CSIC, Salamanca, Spain; Molecular Medicine Unit-IBSAL, Department of Medicine, University of Salamanca, Spain. Electronic address: ttcc@seom.org.

Abstract

OBJECTIVES:

To examine the relationship between polymorphisms of the epidermal growth factor receptor (EGFR) pathway and toxicity in head and neck squamous cell carcinoma (HNSCC) patients treated with cetuximab.

MATERIAL AND METHODS:

Multicenter, retrospective, observational pilot study which included 110 patients with histologically-confirmed human papillomavirus (HPV) negative HNSCC in locally advanced stages (III-IVA-B) and who were treated with chemotherapy and radiotherapy plus cetuximab between 2003 and 2013. Genetic analyses for single nucleotide polymorphisms (SNP) in genes EGFR, CCDN1, FCGR2A, FCGR3A and KRAS-LCS6 were performed though available allelic discrimination assay and/or polymerase chain reaction-restriction fragment length polymorphism methods.

RESULTS:

Acneiform rash was observed in 55.5% of patients, dry skin in 45.5% and pruritus in 20.9%. A significant association with dry skin and global cetuximab-related toxicity was observed for the KRAS-LCS6 (rs61764370) variant (p<0.05); carriers of the G allele (genotypes TG+GG) in the dominant model were observed to have a decreased susceptibility of developing dry skin (OR=0.287 [95%CI=0.119-0.695]). Carriers of the A (GA+AA) allele for EGFR (rs2227983) showed a decreased risk of suffering from pruritus (OR=0.345 [0.124-0.958]). Similarly, KRAS (rs1801274) was related with lower global cetuximab-related toxicity (OR=0.266 [0.114-0.622]).

CONCLUSION:

This pilot study provides preliminary evidence supporting genetic variation of EGFR (rs2227983), KRAS (rs61764370) and FCGR2A (rs180127) as useful biomarkers for predicting reduced skin toxicity in HNSCC patients treated with a cetuximab-based therapy. Alternative therapeutic options should be explored for these patients.

KEYWORDS:

CCDN1; Cetuximab; EGFR; Epidermal growth factor receptor (EGFR); FCGR2A; FCGR3A; Head and neck squamous cell carcinoma (HNSCC); KRAS-LCS6; Polymorphism; SNP; Toxicity

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