Correlation between polymorphisms of the reduced folate carrier gene (SLC19A1) and survival after pemetrexed-based therapy in non-small cell lung cancer: a North Central Cancer Treatment Group-based exploratory study.

Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer
Araba A AdjeiAlex A Adjei

Abstract

To correlate polymorphisms in genes involved in the transport, activation, and inactivation of pemetrexed with the outcome of patients with advanced non-small cell lung cancer (NSCLC) treated with pemetrexed. Data from a phase II NSCLC trial evaluating the optimal schedule of gemcitabine and pemetrexed were used. All patients with available DNA were genotyped for polymorphisms in FPGS, GGH, and SLC19A1 genes. Patients with various genotypes were compared for efficacy and adverse events resulting from pemetrexed. Fifty-four patients had genotype results for all polymorphisms studied. Patients with the homozygous variant genotypes for SLC19A1 IVS4(2117) C>T, IVS5(9148) C>A, and wild-type genotype for exon6(2522) C>T had a significantly better overall survival compared with their counterparts (median overall survival in months: 8.9 [CC] versus 14.0 [CT] versus 16.7 [TT]; 9.4 [CC] versus 10.3 [CA] versus 22.7 [AA]; and 22.7 [CC] versus 10.3 [CT] versus 9.4 [TT] respectively; all log rank p = 0.03). Patients with the heterozygous TC genotype for GGH IVS5(1042) T>C had greater rates of confirmed response + stable disease compared with the TT genotype (85% versus 60%; odds ratio = 4.0; p = 0.06). A greater risk for grade 3/4 SGPT (ALT...Continue Reading

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Citations

Jul 31, 2012·Pharmacogenomics·Elisa GiovannettiGodefridus J Peters
Jan 17, 2012·Cancer Research and Treatment : Official Journal of Korean Cancer Association·Dal Yong KimJung Shin Lee
Jan 14, 2016·Expert Opinion on Drug Metabolism & Toxicology·Mariacarmela SantarpiaElisa Giovannetti
Jan 15, 2014·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Grace K DyNithya Ramnath
Aug 27, 2014·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Grace K DyAlex A Adjei
Aug 6, 2013·Investigational New Drugs·Carlos Alvarez-FernandezEmilio Esteban-Gonzalez
Aug 15, 2012·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Marcello TiseoAndrea Ardizzoni
Aug 9, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Cristina Pérez-RamírezMiguel Ÿngel Calleja-Hernández
Oct 12, 2011·Investigational New Drugs·George R Blumenschein
Feb 21, 2021·Archives of Pharmacal Research·Hye-Young Min, Ho-Young Lee

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