We examined the influence of the UGT1A1 gene promoter polymorphism in the toxicity profile, in the response rate and in the overall survival (OS) in 95 patients with metastatic colorectal cancer treated with an irinotecan-containing chemotherapy.
UGT1A1(*)28 genotype was determined in 218 patients receiving irinotecan (either first-line therapy with capecitabine or second-line as monotherapy) for metastatic colorectal cancer.
We included 49 patients treated for metastatic colorectal cancer with a combination of 5-fluorouracil and irinotecan; a polymorphism in the UGT1A1 gene (TA repeat in the TATA box) and one in the CES2 gene promoter (830C>G) were studied as potential markers for SN-38 glucuronidation and irinotecan activation, respectively; and the potential activity of CYP3A4 was estimated from cortisol biotransformation into 6beta-hydroxycortisol.
Recommendations from the EGAPP Working Group: can UGT1A1 genotyping reduce morbidity and mortality in patients with metastatic colorectal cancer treated with irinotecan?
The objective of this study was to examine the cost effectiveness of using a pharmacogenetic test for uridine diphosphate glycosyltransferase 1A1*28 (UGT1A1*28) variant homozygosity before administering irinotecan to patients with metastatic colorectal cancer.
SN-38 is inactivated by uridine disphosphate glucuronosyl transferase 1 (UGT1A1) into the inactive compound SN-38G, which is excreted with the bile.This review concentrates on a critical evaluation of UGT1A1 gene polymorphism as a predictor of toxicity and treatment efficacy in patients who received irinotecan for metastatic colorectal cancer.
Genotypes were retrospectively evaluated by gene scan analysis on the ABI 310 sequencer of the TATAA box in the promoter region of the UGT1A1 gene in blood samples from 105 patients who had received 1st line irinotecan-based chemotherapy for mCRC.
PATIENTS AND METHODS Patients undergoing first-line treatment for metastatic colorectal cancer (CRC) eligible for treatment with irinotecan plus infusional fluorouracil/leucovorin (FOLFIRI) were screened for the UGT1A1*28/*28 genotype and excluded from the study.
UDP-glucuronosyltransferase 1A1 (UGT1A1) is a pivotal enzyme involved in metabolism of SN-38, the active metabolite of irinotecan commonly used to treat metastatic colorectal cancer.
The purpose of this pharmacogenetic trial was to study the relevance of thymidylate synthase (TS) genotyping and of the isoform 1A1 of uridine diphosphate glucuronosyltransferase (UGT1A1) in order to tailor a combination chemotherapy regimen of 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) in metastatic colorectal cancer.
However, homozygosity for UGT1A1 28 or UGT1A1 6 and double heterozygosity for both UGT1A1 28 and UGT1A1 6 were significantly associated with severe neutropenia in metastatic colorectal cancer patients (P< 0.001).
Functional polymorphisms of the UGT1A1 gene, particularly the UGT1A1*28 variant, are associated with the severity of the bone marrow suppression in patients with metastatic colorectal cancer receiving irinotecan.
A Phase II study of clinical outcomes of 3-week cycles of irinotecan and S-1 in patients with previously untreated metastatic colorectal cancer: influence of the UGT1A1 and CYP2A6 polymorphisms on clinical activity.
A distinct distribution pattern of UGT1A1 genotypes in Chinese patients might contribute to relatively low toxicity associated with irinotecan and 5-fluorouracil in mCRC patients.
In this study, we determined the dose, efficacy, and tolerability of irinotecan according to UGT1A1 genotypes when combined with capecitabine in patients with metastatic colorectal cancer.
We report here a case of a metastatic colorectal cancer patient who is heterozygous for the UGT1A1 28 polymorphism (TA 6/7) as well as the UGT1A1 6 polymorphism (G/A).
Patients with mCRC undergoing UGT1A1 genotyping may receive escalated doses of irinotecan to obtain a better clinical response/outcome with comparable toxicities.
To report a metastatic colorectal cancer patient with hyperbilirubinemia treated with a combination of bevacizumab and FOLFIRI (5-fluorouracil, leucovorin, and irinotecan) using uridine diphosphate glucuronosyl transferase (UGT1A1) genotyping.
UGT1A1*6 (211G>A), UGT1A1*28 (TA6>TA7), UGT1A1*60 (-3279T>G), UGT1A7 (387T>G), UGT1A7 (622T>C), and UGT1A9*1b (-118T9>T10, also named *22) were genotyped in 123 patients with metastatic colorectal cancer who had received irinotecan-based chemotherapy.