Pharmacogenetic study in gastric cancer patients treated with adjuvant fluorouracil/leucovorin or epirubicin/cisplatin/fluorouracil before and after chemoradiation on CALGB 80101 (Alliance).

Journal Article (Journal Article)

There is a lack of pharmacogenetic predictors of outcome in gastric cancer patients. The aim of this study was to assess previously identified candidate genes associated with 5-fluorouracil (5-FU), cisplatin, or epirubicin toxicity or response in a cohort of resected gastric cancer patients treated on CALGB (Alliance) 80101. Gastric or gastroesophageal cancer patients randomized to adjuvant 5-FU/leucovorin or epirubicin/cisplatin/5-FU before and after 5-FU chemoradiation were genotyped for single nucleotide polymorphisms (SNPs) in GSTP1 (rs1695), ERCC1 (rs11615 and rs3212986), XRCC1 (rs25487), UGT2B7 (rs7439366) and the 28 base-pair tandem repeats in TYMS (rs34743033). Logistic regression and log rank tests were used to assess the association between each SNP and incidence of grade 3/4 neutropenia and leukopenia, overall (OS) and progression-free survival (PFS), respectively. Toxicity endpoint analyses were adjusted for the treatment arm, while OS and PFS were also adjusted for performance status, sex, age, lymph node involvement, and primary tumor site and size. Of 281 subjects with successful genotyping results and available clinical (toxicity and efficacy) data, 166 self-reported non-Hispanic White patients were included in the final analysis. There was a lack of evidence of an association among any SNPs tested with grade 3/4 neutropenia and leukopenia or OS and PFS. Age, lymph node involvement, and primary tumor size were significantly associated with OS and PFS. This study failed to confirm results of previous gastric cancer pharmacogenetic studies.

Full Text

Duke Authors

Cited Authors

  • Patel, JN; Jiang, C; Owzar, K; Mulkey, F; Luzum, JA; Mamon, HJ; Haller, DG; Dragovich, T; Alberts, SR; Bjarnason, G; Willet, CG; Niedzwiecki, D; Enzinger, P; Ratain, MJ; Fuchs, C; McLeod, HL

Published Date

  • December 1, 2021

Published In

Volume / Issue

  • 31 / 9

Start / End Page

  • 215 - 220

PubMed ID

  • 34149004

Pubmed Central ID

  • PMC8490297

Electronic International Standard Serial Number (EISSN)

  • 1744-6880

Digital Object Identifier (DOI)

  • 10.1097/FPC.0000000000000442

Language

  • eng

Conference Location

  • United States