ABSTRACT
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.
Subject(s)
Antineoplastic Agents/adverse effects , Drug-Related Side Effects and Adverse Reactions/diagnosis , Lung Neoplasms/drug therapy , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Pemetrexed/adverse effects , Severity of Illness Index , Thymidylate Synthase/genetics , Adult , Aged , Antineoplastic Agents/administration & dosage , Drug-Related Side Effects and Adverse Reactions/etiology , Female , Follow-Up Studies , Genotype , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Middle Aged , Pemetrexed/administration & dosage , Polymorphism, Single Nucleotide , Predictive Value of TestsABSTRACT
En la actualidad, muchos pacientes con fibrilación auricular son anticoagulados por largos períodos. Durante este tiempo pueden ser sometidos a procedimientos invasivos. A partir de una viñeta clínica, un médico se plantea el impacto de utilizar o no heparina de bajo peso molecular como puente farmacológico al momento de suspender la anticoagulación oral. Luego de realizar una búsqueda ad hoc, un ensayo clínico aleatorizado de no inferioridad demuestra que en pacientes con fibrilación auricular, con puntajes de riesgo tromboembólico (CHADS2) intermedios a bajos que requieren una interrupción temporal del tratamiento con warfarina para un procedimiento invasivo electivo, la estrategia de no reemplazar la anticoagulación oral con heparina de bajo peso molecular no resultó inferior (o menos efectiva) para la prevención de tromboembolismo arterial, y disminuyó además el riesgo de sangrado mayor en comparación al uso de un puente con esta medicación. (AU)
Many patients with atrial fibrillation are anticoagulated for long periods. During this time they may be subjected to invasive procedures. From a clinical vignette, a physician discusses the impact of using (or not) low molecular weight heparin as a pharmacological bridge at the time of suspending oral anticoagulation. After conducting a bibliographic search, a no inferiority randomized clinical trial showed that in patients with atrial fibrillation with intermediate to low thromboembolic risk (CHADS2) requiring a temporary interruption of warfarin therapy for an elective invasive procedure, the strategy of with holding low molecular weight heparin bridging was not inferior (or less effective) for the prevention of arterial thromboembolism than its use, also decreasing the risk of major bleeding. (AU)
