Journal
THORAX
Volume 76, Issue 11, Pages 1150-1153Publisher
BMJ PUBLISHING GROUP
DOI: 10.1136/thoraxjnl-2020-216504
Keywords
lung cancer chemotherapy; lung cancer; clinical epidemiology; non-small cell lung cancer
Categories
Funding
- ZonMw, the Netherlands [152001017]
- Innovative Medicines Initiative 2 Joint Undertaking [116 030]
- European Union
- EFPIA
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This study investigated the association of gene polymorphisms with treatment effectiveness and toxicity in non-small-cell lung cancer patients receiving pemetrexed treatment, revealing a significant association between ATIC (rs12995526) and overall survival, as well as a strong correlation between this gene polymorphism and severe chemotherapy-related adverse events and side effects.
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.
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