Pemetrexed Plus Cisplatin Versus Gemcitabine Plus Cisplatin According to Thymidylate Synthase Expression in Nonsquamous Non–Small-Cell Lung Cancer: A Biomarker-Stratified Randomized Phase II Trial

Sun, Jong‐Mu; Ahn, Jin Seok; Jung, Sin‐Ho; Sun, Jiyu; Ha, Sang Yun; Han, Joungho; Park, Keunchil; Ahn, Myung‐Ju

doi:10.1200/jco.2014.59.9324

Cited by 59 publications

(65 citation statements)

References 20 publications

(27 reference statements)

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“…Some studies such as the published by Chang et al did not show statistically significant results supporting the use of TS as a potential biomarker [29]. A very recent prospective study stratified the patients according to TS expression by IHC showed better response rate and progressionfree survival for pemetrexed/cisplatin in the group lacking TS expression [30]. Nevertheless, this is not yet a standard recommendation for clinical practice.…”

Section: Pemetrexedmentioning

confidence: 93%

Pharmacogenomics in the Treatment of Lung Cancer: an Update

et al. 2015

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Significant advances have been made in the analysis of the human genome in the first decades of the 21st century and understanding of tumor biology has matured greatly. The identification of tumor-associated mutations and the pathways involved has led to the development of targeted anticancer therapies. However, the challenge now in using chemotherapy to treat nonsmall-cell lung cancer is to identify more molecular markers predictive of drug sensitivity and determine the optimal drug sequences in order to tailor treatment to each patient. This approach could permit selection of patients who could benefit most from a specific type of chemotherapy by matching their tumor and individual genetic profile. Nevertheless, this potential has been limited so far by reliance on the single biomarker approach, though this is now on the way to being overcome through whole genome studies.

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Section: Pemetrexedmentioning

confidence: 93%

Pharmacogenomics in the Treatment of Lung Cancer: an Update

et al. 2015

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“…More recently, Sun and collaborators [39] reported data from an observational phase II study where they prospectively investigated the correlation between tumor baseline expression of TS and outcome in patients with nonsquamous NSCLC randomly assigned to either pemetrexed/cisplatin or gemcitabine/cisplatin treatment. Low-TS protein levels were predictive of significantly higher response rates and longer progressionfree survival (PFS) in patients treated with pemetrexed/cisplatin compared to the gemcitabine/cisplatin group.…”

Section: Pharmacogenetics Of Pemetrexedmentioning

confidence: 99%

On the pharmacogenetics of non-small cell lung cancer treatment

Santarpía

Rolfo

Peters

et al. 2016

Expert Opinion on Drug Metabolism & Toxicology

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Introduction. Despite many clinical efforts, non-small-cell lung cancer (NSCLC) has a dismal 5-year survival rate of 16%, and high incidence of recurrence. The success of biologically targeted agents, as well as the activity of well-established chemotherapeutic regimens, has been limited by inherited/ acquired resistance, and biomarkers to adapt the prescription of anticancer drugs to patients' features are urgently warranted. Areas covered. In oncology, pharmacogenetics should provide the way to select patients who may benefit from a specific therapy that best match the individual and tumor genetic profile, thus allowing maximum activity and minimal toxicity. The present review summarizes the main findings on NSCLC pharmacogenetics, critically reappraising the most important studies on polymorphisms correlated with outcome of pemetrexed and EGFR-inhibitors, and provides perspective on clinical application of genomic tests for treatment decision-making. Expert Opinion. A major challenge in NSCLC is the identification of subgroups of diseases/patients that will truly benefit from specific treatments. Ideally, convenient and minimally invasive tests to decipher biomarkers of chemosensitivity/resistance and toxicity should be developed alongside novel anticancer treatments. Integration with the latest generation of whole-genome analyses and liquid biopsies as well as prospective validation in large cohorts of patients will overcome the limitations of the traditional pharmacogenetic approaches. ARTICLE HISTORY

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“…However, the efficacy of this preferred chemotherapeutic regimen is very limited, with response rates of 30% to 40%, and progressionfree survival (PFS) of about 4-6 months (3)(4)(5). Despite a large number of promising studies demonstrating the expression level of enzymes targeted by pemetrexed (6,7) and enzymes involved in nucleotide excision repair (NER) of DNA-platinum adducts (8) can be used to predict response to pemetrexed plus cisplatin treatment, the translation of these scientific data from bench to the bedside has not yet occurred. The detection assays, tissue types and antibodies used in previous studies, which lead to inconsistent results, needed to be standardized in all current clinical trials (9).…”

Section: Introductionmentioning

confidence: 99%

Prediction of Chemotherapeutic Efficacy in Non–Small Cell Lung Cancer by Serum Metabolomic Profiling

Tian

Wang

Liu

et al. 2018

Clinical Cancer Research

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In clinical practice, there are currently no validated biomarkers that can, prior to treatment, reliably indicate the intrinsically sensitive or resistant features of a non-squamous NSCLC patient to pemetrexed plus platinum doublet chemotherapy. In this study, we investigated the metabolic characteristics of a large cohort of pre-chemotherapeutic serum samples (354 cases) and found tight associations between small metabolite subsets and the responses of patients to this cytotoxic drug combination. We developed an effective discriminant model employing a seven-metabolite panel (Hypotaurine, Uridine, Dodecanoylcarnitine, Choline, Dimethylglycine, Niacinamide, L-palmitoylcarnitine) that can predict the efficacy of this chemotherapeutic regimens, prior to treatment, with a sensitivity of 90.8% and specificity of 79.5%. We also identified three one-carbon metabolism-involved metabolites including choline, betaine and DMG that are potentially associated with drug resistance to pemetrexed. This serum-based biomarker study can be easily applied in clinical practice and personalize treatment decisions. Conclusion:This study developed an effective and convenient discriminant model that can accurately predict the efficacy and survival outcomes of pemetrexed plus platinum doublet chemotherapy prior to treatment delivery.

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Pemetrexed Plus Cisplatin Versus Gemcitabine Plus Cisplatin According to Thymidylate Synthase Expression in Nonsquamous Non–Small-Cell Lung Cancer: A Biomarker-Stratified Randomized Phase II Trial

Cited by 59 publications

References 20 publications

Pharmacogenomics in the Treatment of Lung Cancer: an Update

Pharmacogenomics in the Treatment of Lung Cancer: an Update

On the pharmacogenetics of non-small cell lung cancer treatment

Prediction of Chemotherapeutic Efficacy in Non–Small Cell Lung Cancer by Serum Metabolomic Profiling

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