Thymidylate synthase polymorphisms in genomic DNA as clinical outcome predictors in a European population of advanced non-small cell lung cancer patients receiving pemetrexed

BACKGROUND: We studied whether thymidylate synthase (TS) genotype has an independent prognostic/predictive impact on a European population of advanced non-small cell lung cancer (NSCLC) patients receiving pemetrexed. METHODS: Twenty-five patients treated with pemetrexed-based regimens were included....

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Detalles Bibliográficos
Autores: Arevalo, E. (Estefanía)|||/items/0337f9af-82d7-43a9-b761-96c1ac44d77a, Castañón-Álvarez, E. (Eduardo)|||/items/6ef1df2b-d729-4ca8-af2e-dd81758ddd7a, Lopez, I. (Inés)|||/items/0353c30a-047c-4379-8b4e-98084ec19f11, Salgado, J. (Josefa)|||/items/833d1e86-a94a-4575-93cb-f90ea6c17abe, Collado, V. (Víctor)|||/items/114c5340-2612-4b90-a6c2-056d25d40a92, Santisteban-Eslava, M. (Marta)|||/items/563d2cef-8a22-4110-97f4-8e16eac15419, Rodriguez-Ruiz, M.E. (María Esperanza)|||/items/bb89f8c4-6380-4de3-8dd0-877dbf28ef44, Martin, P. (Patricia)|||/items/e12aa86b-eea2-4636-abeb-8234adfc8af2, Zubiri, L. (Leire)|||/items/ad94de3b-37c7-4c56-8e35-a9ba84c88cdf, Patiño-García, A. (Ana)|||/items/d68c74f1-df22-4e04-9b77-9cf48fd87b46, Rolfo, C. (Christian)|||/items/cd619c0a-09bd-4d04-a03f-367c9d763138, Gil-Bazo, I. (Ignacio)|||/items/a92277a7-0a96-4e2f-9bb0-8ac5d222270b
Tipo de recurso: artículo
Fecha de publicación:2014
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/36252
Acceso en línea:https://hdl.handle.net/10171/36252
Access Level:acceso abierto
Palabra clave:Non-small cell lung cancer (NSCLC)
European population
Thymidylate synthase
Genotype
Descripción
Sumario:BACKGROUND: We studied whether thymidylate synthase (TS) genotype has an independent prognostic/predictive impact on a European population of advanced non-small cell lung cancer (NSCLC) patients receiving pemetrexed. METHODS: Twenty-five patients treated with pemetrexed-based regimens were included. Genomic DNA was isolated prior to treatment. The variable number of tandem repeat (VNTR) polymorphisms, the G > C single nucleotide polymorphisms (SNP) and the TS 6-bp insertion/deletion (6/6) in the 3' untranslated region (UTR) polymorphisms were analyzed and correlated with overall response rate (ORR), progression-free survival (PFS), overall-survival (OS) and toxicity. RESULTS: The genotype +6/+6 predicted a higher ORR among active/former smokers compared to +6/-6 genotype (100% vs. 50%; p = 0.085). Overall, the 3R/3R genotype predicted a higher ORR (100%) over the rest VNTR polymorphisms (p = 0.055). The presence of 3R/3R genotype significantly correlated with a superior ORR in patients without EGFR activating mutations (100%) compared to 2R/2R, 2R/3R and 3R/4R genotype (77.8%, 33.3% and 0% respectively; p = 0.017). After a median follow-up of 21 months, a trend towards a better PFS, although not significant, was found among subjects showing 3R/3R polymorphisms (p = 0.089). A significantly superior OS was found in patients showing 3R/3R genotype rather than other VNTR polymorphisms (p = 0.019). No significant correlation with the toxicity was observed. CONCLUSION: In our series, 3R/3R polymorphism correlated with a superior OS. Also, this polymorphism, when associated to wild type EGFR, was related to a higher ORR to pemetrexed. Toxicity was not significantly correlated with a specific TS genotype.

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