RESUMO
Pemetrexed is an antimetabolite approved for treatment of non-small cell lung cancer. Harbouring interindividual variability in both the pharmacokinetic and pharmacogenetic profiles may lead to life-threatening toxicities. A prospective cohort study of adult patients initiating treatment with pemetrexed in combination with platinum between 2013 and 2015 were follow up. Primary exposure were the methylenetetrahydrofolate reductase (MTHFR) single base polymorphisms in exon 4 and 7 and 5'-UTR- thymidylate synthase (TYMS) VNTR genotypes, in addition to baseline clinical and demographic variables. We used a Cox regression model to evaluate patient's survival and toxicity experience and its association with both baseline characteristics, and a-priori determined genetic polymorphisms. Seventy two patients were included, 52.7% developed severe hematologic toxicity during follow-up. None of the tested genotypes were significantly associated with the main outcome on multivariate analysis, nor other basal clinical variables. Overall survival between patients experiencing the outcome was not different from those without it, but hospital admissions were more frequent. MTHFR and 5'-UTR-TYMS genotypes were not useful for predicting high grade toxicity events in patients under treatment with pemetrexed.
Assuntos
Antineoplásicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Pemetrexede/efeitos adversos , Índice de Gravidade de Doença , Timidilato Sintase/genética , Adulto , Idoso , Antineoplásicos/administração & dosagem , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Seguimentos , Genótipo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Pemetrexede/administração & dosagem , Polimorfismo de Nucleotídeo Único , Valor Preditivo dos TestesRESUMO
En este artículo, el autor reflexiona sobre las expectativas de los profesionales de la salud acerca de la evidencia para recomendar tratamiento farmacológico a los pacientes con COVID-19. (AU)
In this article, the author reflects on the expectations of health professionals regarding the evidence to recommend pharmacological treatment to patients with COVID-19. (AU)