Relationship between UGT1A1*6/*28 polymorphisms and severe toxicities in Chinese patients with pancreatic or biliary tract cancer treated with irinotecan-containing regimens.
Drug Des Devel Ther
; 9: 3677-83, 2015.
Article
in En
| MEDLINE
| ID: mdl-26229432
ABSTRACT
PURPOSE:
The aim of this retrospective study was to investigate the relationship between UGT1A1 polymorphisms and toxicities in Chinese patients with pancreatic or biliary tract cancer receiving irinotecan-containing regimens as the second- or third-line chemotherapy. PATIENTS ANDMETHODS:
A total of 36 patients with unresectable pancreatic cancer and 12 patients with unresectable biliary tract cancer were included. Approximately 33 patients were treated with FOLFIRI regimen, a chemotherapy regimen, where FOL stands for folinic acid, F for fluorouracil, and IRI for irinotecan (irinotecan 180 mg/m(2) at day 1, CF 200 mg/m(2) at day 1-2, 5-FU 400 mg/m(2) at day 1-2, followed by continuous infusion of 5-FU 600 mg/m(2) for 22 hours at day 1-2, every 2 weeks). The other 15 patients were treated with irinotecan monotherapy (180 mg/m(2), every 2 weeks). UGT1A1*6/*28 polymorphisms were detected by direct sequencing.RESULTS:
The frequencies of GG, GA, AA genotypes for UGT1A1*6 were 70.8% (n=34), 25.0% (n=12), and 4.2% (n=2), respectively. And those of TA6/TA6, TA6/TA7, TA7/TA7 for UGT1A1*28 were 79.2% (n=38), 18.8% (n=9), and 2.0% (n=1), respectively. A total of 22 patients (45.8%) had grade III-IV neutropenia, and six patients (12.5%) experienced grade III-IV diarrhea. The incidence of grade III-IV neutropenia in patients with UGT1A1*6 GA or AA genotype was 71.4%, which was significantly higher than that with GG genotype (35.3%, P=0.022). No relationship was found between grade III-IV neutropenia and UGT1A1*28 polymorphism. The statistical analysis between grade III-IV diarrhea and UGT1A1*6/*28 polymorphisms was not conducted in view of the limited number of patients.CONCLUSION:
In Chinese patients with pancreatic or biliary tract cancer administered irinotecan-containing regimens, those with UGT1A1*6 variant may have a high risk of severe neutropenia.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pancreatic Neoplasms
/
Biliary Tract Neoplasms
/
Camptothecin
/
Glucuronosyltransferase
Type of study:
Observational_studies
/
Risk_factors_studies
Aspects:
Patient_preference
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Drug Des Devel Ther
Journal subject:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Year:
2015
Document type:
Article