Open AccessUGT 1A1 polymorphisms in rectal cancer associated with the efficacy and toxicity of preoperative chemoradiotherapy using irinotecan
Author(s) -
Kimura Kei,
Yamano Tomoki,
Igeta Masataka,
Imada Ayako,
Jihyung Song,
Babaya Akihito,
Hamanaka Michiko,
Kobayashi Masayoshi,
Tsukamoto Kiyoshi,
Noda Masafumi,
Ikeda Masataka,
Tomita Naohiro
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13807
Subject(s) - irinotecan , medicine , chemoradiotherapy , gastroenterology , neutropenia , colorectal cancer , tegafur , toxicity , oncology , surgery , cancer
The purpose of the present study was to assess the efficacy and toxicity of preoperative chemoradiotherapy using irinotecan against locally advanced lower rectal cancer according to UDP ‐glucuronosyltransferase 1A1 ( UGT 1A1 ) polymorphisms. Between 2009 and 2016, 46 patients with resectable rectal cancer (T3‐T4, N0‐N2, M0) received preoperative chemoradiotherapy consisting of 80 mg/m 2 per day tegafur/gimeracil/oteracil (S‐1; days 1‐5, 8‐12, 22‐26, and 29‐33), 60 mg/m 2 per day irinotecan (days 1, 8, 22, and 29), and 45 Gy radiation (1.8 Gy/day, 5 days per week for 5 weeks). Six to eight weeks after completing chemoradiotherapy, total mesorectal excision was carried out. Patients with UGT 1A1 polymorphisms were divided into WT (n = 26), heterozygous (n = 15), and homozygous (n = 5) groups, the latter including double heterozygosities. We evaluated associations between clinical characteristics, including UGT 1A1 polymorphisms, and chemoradiotherapy efficacy and toxicity. Incidence rates of grade 3+ neutropenia and diarrhea were 17.0% and 30.4%, respectively. Relative dose intensity was 89.3%. Pathological complete response rate (grade 3) was 26.1%, and the good response (grade 2/3) rate was 84.8%. UGT 1A1 polymorphisms were significantly associated with neutropenia and pathological good responses, but not with diarrhea. UGT 1A1 polymorphism was the only predictive factor for pathological good responses. Our results indicate that UGT 1A1 polymorphism is a predictive factor to determine the clinical efficacy of preoperative chemoradiotherapy and hematological toxicity induced by chemoradiotherapy using irinotecan in locally advanced rectal cancer patients.