Author:
Visser Sabine,Koolen Stijn,van Donk Nadine,van Walree Nico,van der Leest Cor,Cornelissen Robin,van Schaik Ron,Mathijssen Ron,Aerts Joachim,Stricker Bruno H
Abstract
Patients with advanced non-small-cell lung cancer who are treated with pemetrexed display a wide variation in clinical response and toxicity. In this prospective, multicentre cohort study, we investigated the association with treatment effectiveness and toxicity of 10 polymorphisms in nine candidate genes, covering the folate pathway (MTHFR), cell transport (SLC19A1/ABCC2/ABCC4), intracellular metabolism (FPGS/GGH) and target enzymes (TYMS/DHFR/ATIC) of pemetrexed. Adjusted for sex, ECOG performance score and disease stage, the association between ATIC (rs12995526) and overall survival (HR 1.59, 95% CI 1.06 to 2.39) was significant. Regarding toxicity, this ATIC polymorphism was significantly associated with severe laboratory (p=0.014) and clinical (p=0.016) chemotherapy-related adverse events, severe neutropenia (p=0.007) and all-grade diarrhoea (p=0.034) in multivariable analyses.
Funder
Innovative Medicines Initiative
ZonMw
Subject
Pulmonary and Respiratory Medicine
Reference11 articles.
1. Systemic therapy for stage IV non-small-cell lung cancer: American Society of clinical oncology clinical practice guideline update;Hanna;J Clin Oncol,2017
2. A semimechanistic-physiologic population pharmacokinetic/pharmacodynamic model for neutropenia following pemetrexed therapy
3. NCI, NIH D . Common terminology criteria for adverse events v4.0. NIH Publ, 2009. Available: http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf
4. Prognostic significance of the polymorphisms in thymidylate synthase and methylenetetrahydrofolate reductase gene in lung cancer;Takehara;Anticancer Res,2005
5. Pemetrexed exposure predicts toxicity in advanced non-small-cell lung cancer: a prospective cohort study;Visser;Eur J Cancer,2019
Cited by
5 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献