Epidermal growth factor receptor polymorphisms and risk for toxicity in paediatric patients treated with gefitinib.

European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)
Trevor McKibbinClinton F Stewart

Abstract

To investigate associations between germline genetic variations in the epidermal growth factor receptor (EGFR) and toxicity in paediatric patients treated with gefitinib. Gefitinib treatment and toxicity data from five paediatric clinical trials were combined. EGFR genotypes evaluated included -191C>A, -216G>T, Arg497Lys and intron 1 CA sequence repeat number. The genetic variations were evaluated for associations with grade one or greater rash or diarrhoea during the first course of treatment. The analysis included 110 patients, 60 (55%) with grade one or greater rash and 47 (43%) with grade one or greater diarrhoea. Among patients with the -216 GG (n=51), GT (n=41) and TT (n=16) genotypes, grade one or greater rash occurred in 52.9%, 46.3% and 87.5% of patients (p=0.003, recessive model), respectively. Diarrhoea occurred in 27.5%, 58.5% and 43.8% of patients with respective GG, GT and TT genotypes (p=0.004, dominant model). The -191C>A, intron 1 CA repeat number and Arg497Lys genotypes were not significantly associated with either rash or diarrhoea. EGFR -216 and -191 polymorphisms were in linkage disequilibrium (D'=0.66, p=0.01). The haplotype (-191C, -216T) was associated with increased risk for rash (p=0.049), but was not ...Continue Reading

References

Oct 11, 1994·Proceedings of the National Academy of Sciences of the United States of America·T MoriaiM Korc
Aug 18, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Román Pérez-SolerPhilip Bonomi
Dec 2, 2004·Nature Reviews. Cancer·Roy S HerbstJosé Baselga
Feb 16, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Sae-Won HanNoe Kyeong Kim
May 5, 2005·Journal of the National Cancer Institute·Federico CappuzzoMarileila Varella-Garcia
Jun 16, 2005·Journal of the National Cancer Institute·Daphne A Haas-KoganDavid Stokoe
Dec 26, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Burkhard BrandtHorst Buerger
Jun 19, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Wei-Shu WangYeu Su
Aug 21, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Wu ZhangHeinz-Josef Lenz
Mar 4, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Charles M RudinMark J Ratain
Nov 11, 2008·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Chin-Lun HuangPan-Chyr Yang
Aug 19, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Wayne L FurmanClinton F Stewart
Aug 21, 2009·The New England Journal of Medicine·Tony S MokMasahiro Fukuoka

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Citations

Dec 14, 2011·The Pharmacogenomics Journal·S ParmarJ C Stingl
May 25, 2011·International Journal of Radiation Oncology, Biology, Physics·Kim De RuyckHubert Thierens
Jul 13, 2011·Expert Review of Molecular Diagnostics·Alexander Picker, David B Jackson
Sep 21, 2013·Therapeutic Drug Monitoring·Debra H JosephsRobert J Flanagan
Aug 12, 2020·Cancer Science·Chihiro Udagawa, Hitoshi Zembutsu
Nov 9, 2018·Analytical Cellular Pathology (Amsterdam)·Vladimir JurišićNataša Djordjevic
Dec 31, 2020·Pediatric Dermatology·Valerie M CarlbergDeepti Gupta

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