Pharmacogenetic study in gastric cancer patients treated with adjuvant fluorouracil/leucovorin or epirubicin/cisplatin/fluorouracil before and after chemoradiation on CALGB 80101 (Alliance).
Journal
Pharmacogenetics and genomics
ISSN: 1744-6880
Titre abrégé: Pharmacogenet Genomics
Pays: United States
ID NLM: 101231005
Informations de publication
Date de publication:
01 12 2021
01 12 2021
Historique:
pubmed:
22
6
2021
medline:
14
1
2022
entrez:
21
6
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34149004
doi: 10.1097/FPC.0000000000000442
pii: 01213011-202112000-00005
pmc: PMC8490297
mid: NIHMS1709442
doi:
Substances chimiques
X-ray Repair Cross Complementing Protein 1
0
XRCC1 protein, human
0
Epirubicin
3Z8479ZZ5X
Cisplatin
Q20Q21Q62J
Leucovorin
Q573I9DVLP
Fluorouracil
U3P01618RT
Banques de données
ClinicalTrials.gov
['NCT00052910']
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
215-220Subventions
Organisme : NCI NIH HHS
ID : U10 CA180868
Pays : United States
Organisme : NIGMS NIH HHS
ID : U01 GM063340
Pays : United States
Organisme : NIGMS NIH HHS
ID : U01 GM061393
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180857
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA233160
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA233373
Pays : United States
Organisme : NIGMS NIH HHS
ID : U01 GM061390
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180882
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180820
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA233253
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180888
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180821
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA233337
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180863
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA233180
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA196171
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA233327
Pays : United States
Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Références
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68:394–424.
Patel JN, Fuchs CS, Owzar K, Chen Z, McLeod HL. Gastric cancer pharmacogenetics: progress or old tripe? Pharmacogenomics. 2013; 14:1053–1064.
Network NCC. Gastric cancer. In: NCCN Guidelines. Version 3.2019. Plymouth Meeting, PA: National Comprehensive Cancer Network; 2019.
Goekkurt E, Al-Batran SE, Hartmann JT, Mogck U, Schuch G, Kramer M, et al. Pharmacogenetic analyses of a phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil and leucovorin plus either oxaliplatin or cisplatin: a study of the arbeitsgemeinschaft internistische onkologie. J Clin Oncol. 2009; 27:2863–2873.
Goekkurt E, Al-Batran SE, Mogck U, Pauligk C, Hartmann JT, Kramer M, et al. Pharmacogenetic analyses of hematotoxicity in advanced gastric cancer patients receiving biweekly fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT): a translational study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Ann Oncol. 2009; 20:481–485.
Ruzzo A, Graziano F, Kawakami K, Watanabe G, Santini D, Catalano V, et al. Pharmacogenetic profiling and clinical outcome of patients with advanced gastric cancer treated with palliative chemotherapy. J Clin Oncol. 2006; 24:1883–1891.
Smyth E, Zhang S, Cunningham D, Wotherspoon A, Soong R, Peckitt C, et al. Pharmacogenetic analysis of the UK MRC (Medical Research Council) MAGIC trial: association of polymorphisms with toxicity and survival in patients treated with perioperative epirubicin, cisplatin, and 5-fluorouracil (ECF) chemotherapy. Clin Cancer Res. 2017; 23:7543–7549.
Meulendijks D, Rozeman EA, Cats A, Sikorska K, Joerger M, Deenen MJ, et al. Pharmacogenetic variants associated with outcome in patients with advanced gastric cancer treated with fluoropyrimidine and platinum-based triplet combinations: a pooled analysis of three prospective studies. Pharmacogenomics J. 2017; 17:441–451.
Schulz C, Zhang W, Lenz HJ, Neumann J, Kullmann F, Kunzmann V, et al. Germline polymorphisms (SNPs) to predict toxicity and efficacy in FLOT-treated patients with locally advanced gastroesophageal junction or gastric adenocarcinoma—data from the NeoFLOT study. Transl Cancer Res. 2018; 7:1393–1405.
Parmar S, Stingl JC, Huber-Wechselberger A, Kainz A, Renner W, Langsenlehner U, et al. Impact of UGT2B7 His268Tyr polymorphism on the outcome of adjuvant epirubicin treatment in breast cancer. Breast Cancer Res. 2011; 13:R57.
Fuchs CS, Niedzwiecki D, Mamon HJ, Tepper JE, Ye X, Swanson RS, et al. Adjuvant chemoradiotherapy with epirubicin, cisplatin, and fluorouracil compared with adjuvant chemoradiotherapy with fluorouracil and leucovorin after curative resection of gastric cancer: results from CALGB 80101 (Alliance). J Clin Oncol. 2017; 35:3671–3677.
Team RC. A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2015.
Terry MT, Patricia MG. Modeling Survival Data: Extending the Cox Model. New York: Springer; 2000. ISBN 0-387-98784-3.
Warnes G. Package ‘genetics’. In: Population Genetics. 1.3.8.1. 2013.
Xie Y. knitr. A General-Purpose Package for Dynamic Report Generation in R. In: R Package. version 1.12.3. 2016.
Li Q, Yu JJ, Mu C, Yunmbam MK, Slavsky D, Cross CL, et al. Association between the level of ERCC-1 expression and the repair of cisplatin-induced DNA damage in human ovarian cancer cells. Anticancer Res. 2000; 20:645–652.
Zhou W, Gurubhagavatula S, Liu G, Park S, Neuberg DS, Wain JC, et al. Excision repair cross-complementation group 1 polymorphism predicts overall survival in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy. Clin Cancer Res. 2004; 10:4939–4943.
Suk R, Gurubhagavatula S, Park S, Zhou W, Su L, Lynch TJ, et al. Polymorphisms in ERCC1 and grade 3 or 4 toxicity in non-small cell lung cancer patients. Clin Cancer Res. 2005; 11:1534–1538.
Shen J, Desai M, Agrawal M, Kennedy DO, Senie RT, Santella RM, Terry MB. Polymorphisms in nucleotide excision repair genes and DNA repair capacity phenotype in sisters discordant for breast cancer. Cancer Epidemiol Biomarkers Prev. 2006; 15:1614–1619.
Innocenti F, Iyer L, Ramírez J, Green MD, Ratain MJ. Epirubicin glucuronidation is catalyzed by human UDP-glucuronosyltransferase 2B7. Drug Metab Dispos. 2001; 29:686–692.
Ioannidis JP. Why most published research findings are false. Plos Med. 2005; 2:e124.
Thomas F, Hoskins JM, Dvorak A, Tan BR, McLeod HL. Detection of the G>C SNP and rare mutations in the 28-bp repeat of TYMS using gel-based capillary electrophoresis. Pharmacogenomics. 2010; 11:1751–1756.