UGT1A1 polymorphisms in rectal cancer associated with the efficacy and toxicity of preoperative chemoradiotherapy using irinotecan

Autor: Michiko Hamanaka, Akihito Babaya, Kei Kimura, Masafumi Noda, Song Jihyung, Naohiro Tomita, Masayoshi Kobayashi, Masataka Igeta, Kiyoshi Tsukamoto, Tomoki Yamano, Masataka Ikeda, Ayako Imada
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
Cancer Research
Pharmacogenomic Variants
Colorectal cancer
Gastroenterology
0302 clinical medicine
Glucuronosyltransferase
General Medicine
Chemoradiotherapy
Middle Aged
Total mesorectal excision
Neoadjuvant Therapy
Diarrhea
Drug Combinations
Treatment Outcome
Oncology
030220 oncology & carcinogenesis
Toxicity
Female
Original Article
medicine.symptom
medicine.drug
Adult
medicine.medical_specialty
Neutropenia
Irinotecan
Tegafur
Polymorphism
Single Nucleotide
Drug Administration Schedule
03 medical and health sciences
clinical efficacy
Clinical Research
Internal medicine
medicine
Humans
rectal cancer
Aged
business.industry
Rectal Neoplasms
toxicity
Original Articles
medicine.disease
Oxonic Acid
030104 developmental biology
UGT1A1 polymorphism
Dose Fractionation
Radiation
Neoplasm Grading
business
Zdroj: Cancer Science
ISSN: 1349-7006
Popis: 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 (UGT1A1) polymorphisms. Between 2009 and 2016, 46 patients with resectable rectal cancer (T3-T4, N0-N2, M0) received preoperative chemoradiotherapy consisting of 80 mg/m2 per day tegafur/gimeracil/oteracil (S-1; days 1-5, 8-12, 22-26, and 29-33), 60 mg/m2 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 UGT1A1 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 UGT1A1 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%. UGT1A1 polymorphisms were significantly associated with neutropenia and pathological good responses, but not with diarrhea. UGT1A1 polymorphism was the only predictive factor for pathological good responses. Our results indicate that UGT1A1 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.
Databáze: OpenAIRE
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