Pharmacogenetic study of patients with advanced non-small cell lung cancer (NSCLC) treated with second-line pemetrexed or pemetrexed–carboplatin
| العنوان: | Pharmacogenetic study of patients with advanced non-small cell lung cancer (NSCLC) treated with second-line pemetrexed or pemetrexed–carboplatin |
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| المؤلفون: | Jacobus A. Burgers, Godefridus J. Peters, Egbert F. Smit, Elisa Giovannetti, Francesco Di Costanzo, Andrea Ardizzoni, Carmelo Tibaldi, Andrea Camerini, Fausto Barbieri, Marcello Tiseo, Andrew D. Vincent |
| المساهمون: | Medical oncology laboratory, Pulmonary medicine, CCA - Innovative therapy, Tiseo, Marcello, Giovannetti, Elisa, Tibaldi, Carmelo, Camerini, Andrea, Di Costanzo, Francesco, Barbieri, Fausto, Burgers, Jacobus A., Vincent, Andrew, Peters, Godefridus J., Smit, Egbert F., Ardizzoni, Andrea |
| المصدر: | Lung Cancer, 78(1), 92-99. Elsevier Ireland Ltd Tiseo, M, Giovannetti, E, Tibaldi, C, Camerini, A, Di Costanzo, F, Barbieri, F, Burgers, J A, Vincent, A D, Peters, G J, Smit, E F & Ardizzoni, A 2012, ' Pharmacogenetic study of patients with advanced non-small cell lung cancer (NSCLC) treated with second-line pemetrexed or pemetrexed-carboplatin ', Lung Cancer, vol. 78, no. 1, pp. 92-99 . https://doi.org/10.1016/j.lungcan.2012.07.009Test |
| بيانات النشر: | Elsevier BV, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Male, Oncology, Cancer Research, Lung Neoplasms, non-small cell lung cancer (NSCLC), Pharmacology, Thymidylate synthase, Carboplatin, Antineoplastic Agent, Reduced Folate Carrier Protein, chemistry.chemical_compound, Gene Frequency, Glutamates, Retrospective Studie, Carcinoma, Non-Small-Cell Lung, Antineoplastic Combined Chemotherapy Protocols, Allele, Aged, 80 and over, biology, Pharmacogenetic, Hazard ratio, Middle Aged, Treatment Outcome, Pemetrexed, Female, Glutamate, Human, medicine.drug, Adult, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Guanine, Genotype, Non-small cell lung cancer (NSCLC), Antineoplastic Agents, Polymorphism, Single Nucleotide, Internal medicine, medicine, Humans, Alleles, Methylenetetrahydrofolate Reductase (NADPH2), Aged, Neoplasm Staging, Retrospective Studies, Xeroderma Pigmentosum Group D Protein, Antineoplastic Combined Chemotherapy Protocol, business.industry, Proportional hazards model, Thymidylate Synthase, gamma-Glutamyl Hydrolase, MTHFR-C667T polymorphism, medicine.disease, Lung Neoplasm, chemistry, Methylenetetrahydrofolate reductase, biology.protein, business, Pharmacogenetics |
| الوصف: | Purpose To correlate candidate polymorphisms affecting pemetrexed and carboplatin activity with clinical outcome of patients with advanced non-small cell lung cancer (NSCLC) treated in second-line with pemetrexed or pemetrexed plus carboplatin. Methods Functional polymorphisms in thymidylate synthase (TS), reduced folate carrier (RFC), gamma-glutamyl hydrolase (GGH), methylenetetrahydrofolate reductase (MTHFR) and xeroderma pigmentosum group D (XPD) genes were evaluated in 208 patients either treated within randomized phase II trials NVALT-7 and GOIRC-02.2006, comparing second-line pemetrexed with pemetrexed plus carboplatin, or with the same regimens outside of these trials. Univariate and multivariate analyses correlated genotyping data with response, clinical benefit, toxicity, progression-free (PFS) and overall survival (OS) using Pearson- χ 2 test, log-rank test and Cox proportional hazards model. Results Patients harboring the MTHFR-T667T variant had significantly longer PFS (5.4 versus 3.4 months; p =0.012) and OS (16.4 versus 8.5 months; p =0.026) than patients with CC–CT genotypes. No correlation was observed for other polymorphisms, except for XPD-Gln751Gln , which was associated with shorter PFS ( p =0.021) and OS ( p =0.044) in the subgroup of patients treated with pemetrexed plus carboplatin. Multivariate analysis confirmed the independent prognostic significance of MTHFR-C677T both in risk of disease progression ( CC–CT genotypes hazard ratio [HR] 1.94, 95%CI 1.15–3.28; p =0.012) and of death (HR 2.00, 95%CI 1.12–3.54; p =0.018). Conclusions MTHFR-C667T polymorphisms appear to predict survival differences in pemetrexed-treated NSCLC. These results should be validated in larger and adequately designed prospective studies using pemetrexed. |
| وصف الملف: | ELETTRONICO |
| تدمد: | 0169-5002 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9e75b870f6ebcd4b15db069e24f07cf1Test https://doi.org/10.1016/j.lungcan.2012.07.009Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....9e75b870f6ebcd4b15db069e24f07cf1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 01695002 |
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