UGT1A1*1/*28 and *1/*6 genotypes have no effects on the efficacy and toxicity of FOLFIRI in Japanese patients with advanced colorectal cancer.
OBJECTIVE
Differences in efficacy and toxicity between UDP-glucuronosyltransferase (UGT) 1A1*1/*1 and *1/*6 or *1/*28 genotypes remain unclear in Japanese patients.


METHODS
Patients with advanced colorectal cancer who received irinotecan combined with 5-fluorouracil plus l-leucovorin (FOLFIRI) as first-line therapy were divided into two groups: those with UGT1A1*1/*1 genotype and those with UGT1A1*1/*6 or *1/*28 genotype. Efficacy and toxicity were compared between these groups retrospectively.


RESULTS
Forty-two patients (24 *1/*1 and 18 *1/*6 or *1/*28) were evaluated. The response rate was 48% in *1/*1 group and 56% in *1/*6 or *1/*28 group (P = 0.847). Median progression-free survival was 8.6 months in *1/*1 group and 8.5 months in *1/*6 or *1/*28 group (P = 0.888). No hematologic or non-hematologic toxic effects were clearly related to UGT1A1*1/*6 or *1/*28 during the first cycle or throughout the entire course of chemotherapy.


CONCLUSIONS
There were no significant differences in the efficacy or toxicity of FOLFIRI between patients with UGT1A1*1/*1 genotype and those with UGT1A1*1/*6 or *1/*28 genotype. Our results suggest that patients with the latter genotypes can receive FOLFIRI at the same dose of irinotecan as those with the UGT1A1*1/*1 genotype receive.
Department of Medical Oncology, International Medical Center-Comprehensive Cancer Center, Saitama Medical University, Hidaka, Saitama, Japan.
Yu
Y
Sunakawa
Wataru
W
Ichikawa
Ken-Ichi
K
Fujita
Fumio
F
Nagashima
Hiroo
H
Ishida
Keishi
K
Yamashita
Keiko
K
Mizuno
Keisuke
K
Miwa
Kaori
K
Kawara
Yuko
Y
Akiyama
Kazuhiro
K
Araki
Wataru
W
Yamamoto
Toshimichi
T
Miya
Masaru
M
Narabayashi
Yuichi
Y
Ando
Takashi
T
Hirose
Shigehira
S
Saji
Yasutsuna
Y
Sasaki
D000328:Adult; D000368:Aged; D000483:Alleles; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001711:Biotransformation / Q000235:genetics; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D056726:Genetic Association Studies; D014453:Glucuronosyltransferase / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D000077146:Irinotecan; D007564:Japan; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D011355:Prodrugs / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012189:Retrospective Studies; D016019:Survival Analysis; D059004:Topoisomerase I Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000099148:UGT1A1 Enzyme
D002166:Camptothecin; D005472:Fluorouracil; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D002955:Leucovorin; D011355:Prodrugs; D059004:Topoisomerase I Inhibitors; D000099148:UGT1A1 Enzyme