Predictive Value of and Polymorphisms on Irinotecan-Related Toxicities in Patients with Cancer.

There is extensive interindividual variability in response and tolerance to anticancer drugs. This heterogeneity provides a major limitation to the "rational" use of cytotoxic drugs, and it becomes a major problem in oncology giving a narrow therapeutic window with a vital risk. Among these anticancer drugs, irinotecan can cause dose-limiting toxicities, commonly diarrhea and neutropenia. Interaction among pathways of activation/inactivation () and hepatobiliary transport of irinotecan and its metabolites could, in part, explain its interindividual variability. The objective of this study was to perform an exploratory analysis to evaluate the correlation between the genetic polymorphisms of and with the different toxicities associated with irinotecan treatment. Seventy-five patients with solid cancers were included, all were administered an irinotecan-based regimen in both Mission Bay Medical Center; and Zuckerberg San Francisco General Hospital from May 2016 to December 2016. The patients' genotyping was performed for both the *28 polymorphism, and the  - 1549G>A, and  - 1249G>A single nucleotide polymorphism. Comparisons among qualitative data were assessed using the χ-test, and Fisher's exact test in the case of small group sizes. Diarrhea was observed in 40 patients (53.3%), among them only 9 patients had high grades diarrhea (grades III and IV). Grades III/IV of nausea were more frequently associated with the -1549 AA genotype (83.3%  = 0.004) in patients with colorectal cancer. In pancreatic cancer, a significant absence of diarrhea grades III-IV was noted in patients with the 1249 GG genotype compared to the other 1249 genotypes.