Association between UGT1A1 gene polymorphism and safety and efficacy of irinotecan monotherapy as the third-line treatment for advanced gastric cancer.
Adult
Aged
Aged, 80 and over
Antineoplastic Agents, Phytogenic
/ therapeutic use
Biomarkers, Tumor
/ genetics
Female
Follow-Up Studies
Glucuronosyltransferase
/ genetics
Humans
Intestinal Neoplasms
/ drug therapy
Irinotecan
/ therapeutic use
Lymphatic Metastasis
Male
Middle Aged
Polymorphism, Genetic
Prognosis
Retrospective Studies
Salvage Therapy
Stomach Neoplasms
/ drug therapy
Survival Rate
Gastric cancer
Irinotecan
UGT1A1
Journal
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
ISSN: 1436-3305
Titre abrégé: Gastric Cancer
Pays: Japan
ID NLM: 100886238
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
31
08
2018
accepted:
17
12
2018
pubmed:
4
1
2019
medline:
31
12
2019
entrez:
4
1
2019
Statut:
ppublish
Résumé
While uridine diphosphate glucuronosyltransferase (UGT) 1A1 is a key enzyme in the metabolism of irinotecan, relationship between UGT1A1 genotype and safety and efficacy of irinotecan monotherapy in patients with advanced gastric cancer is not clarified. Efficacy and safety in advanced gastric cancer patients, who were tested for UGT1A1*6 and *28 genotype and treated with irinotecan monotherapy as third-line treatment from 2009 to 2014, were evaluated according to the UGT1A1*6 and *28 genotypes. Among 74 patients of the subjects, the genotypes of UGT1A1 were wild-type (WT) in 37 patients (50%), single heterozygosity (SH) in 27 (36.5%) and double heterozygosity or homozygosity (Homo/DH) in 10 (13.5%). The initial dose of irinotecan was reduced in 10 patients (27%) with WT, in 9 (33%) with SH, and in 7 (70%) with Homo/DH. Median overall survival was 6.9 months, 6.3 months, and 2.8 months in the WT, SH and Homo/DH genotypes, associated with median time to treatment failure of 2.4 months, 2.3 months, and 1.3 months, respectively. Among 36 patients with measurable lesion, disease control rates were 47.6%, 41.7% and 33.3% in the WT, SH and Homo/DH genotypes. Grade 3 or higher adverse events of special interest were neutropenia (13%, 22%, and 64% for the WT, SH and Homo/DH genotypes), febrile neutropenia (2%, 7%, and 50%) and diarrhea (6%, 5%, and 21%). The UGT1A1 polymorphism may be related to the clinical outcomes of irinotecan monotherapy as the third-line treatment for advanced gastric cancer.
Sections du résumé
BACKGROUND
While uridine diphosphate glucuronosyltransferase (UGT) 1A1 is a key enzyme in the metabolism of irinotecan, relationship between UGT1A1 genotype and safety and efficacy of irinotecan monotherapy in patients with advanced gastric cancer is not clarified.
METHODS
Efficacy and safety in advanced gastric cancer patients, who were tested for UGT1A1*6 and *28 genotype and treated with irinotecan monotherapy as third-line treatment from 2009 to 2014, were evaluated according to the UGT1A1*6 and *28 genotypes.
RESULTS
Among 74 patients of the subjects, the genotypes of UGT1A1 were wild-type (WT) in 37 patients (50%), single heterozygosity (SH) in 27 (36.5%) and double heterozygosity or homozygosity (Homo/DH) in 10 (13.5%). The initial dose of irinotecan was reduced in 10 patients (27%) with WT, in 9 (33%) with SH, and in 7 (70%) with Homo/DH. Median overall survival was 6.9 months, 6.3 months, and 2.8 months in the WT, SH and Homo/DH genotypes, associated with median time to treatment failure of 2.4 months, 2.3 months, and 1.3 months, respectively. Among 36 patients with measurable lesion, disease control rates were 47.6%, 41.7% and 33.3% in the WT, SH and Homo/DH genotypes. Grade 3 or higher adverse events of special interest were neutropenia (13%, 22%, and 64% for the WT, SH and Homo/DH genotypes), febrile neutropenia (2%, 7%, and 50%) and diarrhea (6%, 5%, and 21%).
CONCLUSIONS
The UGT1A1 polymorphism may be related to the clinical outcomes of irinotecan monotherapy as the third-line treatment for advanced gastric cancer.
Identifiants
pubmed: 30603911
doi: 10.1007/s10120-018-00917-5
pii: 10.1007/s10120-018-00917-5
doi:
Substances chimiques
Antineoplastic Agents, Phytogenic
0
Biomarkers, Tumor
0
Irinotecan
7673326042
UGT1A1 enzyme
EC 2.4.1.-
Glucuronosyltransferase
EC 2.4.1.17
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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