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

Autor: Fernandez-Mateos, J, Seijas-Tamayo, R, Mesia, R, Taberna, M, Borgonon, MP, Perez-Ruiz, E, Klain, JCA, Fernandez, SV, Morillo, ED, Lozano, A, Sarmiento, RG, Cruz-Hernandez, JJ, Spanish Head Neck Canc Cooperative
Rok vydání: 2016
Předmět:
Zdroj: ORAL ONCOLOGY
r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe
instname
ISSN: 1368-8375
Popis: 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 cetuximabrelated 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. (C) 2016 The Authors. Published by Elsevier Ltd.
Databáze: OpenAIRE
Externí odkaz: