Severe toxicity in adult patients with lung cancer under treatment with pemetrexed: a prospective cohort study

• Published in: Journal of chemotherapy (Florence) Vol. 31; no. 2; pp. 95 - 104
• Main Authors: Vázquez, Carolina, Orlova, María, Verzura, María Alicia, Minatta, José Nicolás, Scibona, Paula, Jáuregui, Esteban Gabriel, Díaz de Arce, Heidy, Pallotta, María Guadalupe, Belloso, Waldo Horacio
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 17-02-2019
• Subjects: Adult; Adverse events; Aged; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Drug-Related Side Effects and Adverse Reactions - diagnosis; Drug-Related Side Effects and Adverse Reactions - etiology; Female; Follow-Up Studies; Genotype; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; Middle Aged; MTHFR; NSCLC; Pemetrexed - administration & dosage; Pemetrexed - adverse effects; Pharmacogenetics; Polymorphism, Single Nucleotide; Predictive Value of Tests; Severity of Illness Index; Thymidylate Synthase - genetics; TYMS; MTHFR; Pharmacogenetics; Adverse events; NSCLC; TYMS
• ISSN: 1120-009X; 1973-9478
• DOI: 10.1080/1120009X.2019.1572287

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.