BACKGROUND/AIM: Afatinib, a 2nd generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) used in treatment of non-small cell lung cancer (NSCLC), causes diarrhoea in over 90% of patients. The association of genetic background with diarrhoea is poorly understood. PATIENTS AND METHODS: We evaluated the roles of four single nucleotide polymorphisms (SNPs) in ATP binding cassette subfamily B member 1 (ABCB1) and ATP binding cassette subfamily G member 2 (ABCG2) genes-ABCB1 1236 C>T, 2677 G>T/A, and 3435 C>T, and ABCG2 421 C>A-on treatment-induced diarrhoea in 38 patients with NSCLC treated with afatinib. RESULTS: Diarrhoea occurred more frequently in patients with ABCB1 2677 T(A)/T(A) (14/16, 87.5%) than in patients with non-T(A)/T(A) alleles (8/22, 36.4%) (p=0.003). ABCB1 2677 T(A)/T(A) was significantly predictive of diarrhoea (p=0.002) by multivariable regression analysis. CONCLUSION: Afatinib-induced diarrhoea is associated with the SNP ABCB1 2677 T(A)/T(A). Copyright
BACKGROUND/AIM: Afatinib, a 2nd generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) used in treatment of non-small cell lung cancer (NSCLC), causes diarrhoea in over 90% of patients. The association of genetic background with diarrhoea is poorly understood. PATIENTS AND METHODS: We evaluated the roles of four single nucleotide polymorphisms (SNPs) in ATP binding cassette subfamily B member 1 (ABCB1) and ATP binding cassette subfamily G member 2 (ABCG2) genes-ABCB1 1236 C>T, 2677 G>T/A, and 3435 C>T, and ABCG2 421 C>A-on treatment-induced diarrhoea in 38 patients with NSCLC treated with afatinib. RESULTS:Diarrhoea occurred more frequently in patients with ABCB1 2677 T(A)/T(A) (14/16, 87.5%) than in patients with non-T(A)/T(A) alleles (8/22, 36.4%) (p=0.003). ABCB1 2677 T(A)/T(A) was significantly predictive of diarrhoea (p=0.002) by multivariable regression analysis. CONCLUSION:Afatinib-induced diarrhoea is associated with the SNP ABCB1 2677 T(A)/T(A). Copyright
Authors: James C-H Yang; Lecia V Sequist; Sarayut Lucien Geater; Chun-Ming Tsai; Tony Shu Kam Mok; Martin Schuler; Nobuyuki Yamamoto; Chong-Jen Yu; Sai-Hong I Ou; Caicun Zhou; Daniel Massey; Victoria Zazulina; Yi-Long Wu Journal: Lancet Oncol Date: 2015-06-04 Impact factor: 41.316
Authors: Lecia V Sequist; James Chih-Hsin Yang; Nobuyuki Yamamoto; Kenneth O'Byrne; Vera Hirsh; Tony Mok; Sarayut Lucien Geater; Sergey Orlov; Chun-Ming Tsai; Michael Boyer; Wu-Chou Su; Jaafar Bennouna; Terufumi Kato; Vera Gorbunova; Ki Hyeong Lee; Riyaz Shah; Dan Massey; Victoria Zazulina; Mehdi Shahidi; Martin Schuler Journal: J Clin Oncol Date: 2013-07-01 Impact factor: 44.544
Authors: James Chih-Hsin Yang; Noemi Reguart; Jana Barinoff; Jens Köhler; Martina Uttenreuther-Fischer; Uz Stammberger; Dennis O'Brien; Jürgen Wolf; Ezra E W Cohen Journal: Expert Rev Anticancer Ther Date: 2013-03-18 Impact factor: 4.512