title: Prospective study of the UGT1A1*27 gene polymorphism during irinotecan therapy in patients with lung cancer: Results of Lung Oncology Group in Kyusyu (LOGIK1004B).
abstract: BACKGROUND
  Uridine 5'-diphospho-glucuronosyltransferase 1A1 (UGT1A1*27) is known to impair the effect of UGT in basic research; however, little clinical investigation has been conducted. To evaluate the effect of the UGT1A1*27 polymorphism in irinotecan therapy, we conducted a prospective study.
  
  
  METHODS
  Eligibility criteria included: lung cancer patients; scheduled irinotecan therapy doses of single ≥ 80, combination ≥ 50, radiation with single ≥ 50, or radiation with combination ≥ 40 mg/m(2); age ≥ 20; and Eastern Cooperative Oncology Group performance score (PS) 0-2. Patients were examined for UGT1A1*28 and *6 polymorphisms and received irinotecan. When the UGT1A1*28 polymorphism was detected, a search for UGT1A1*27 was conducted. Fifty patients were enrolled, with 48 patients determined eligible.
  
  
  RESULTS
  UGT1A1 polymorphisms *28/*28, *6/*6, *28/*6, *28/-, *6/-, -/- observed 0 (0%), 1 (2%), 1 (2%), 7 (15%), 17 (35%) and 22 (46%), respectively. UGT1A1*27 were examined in nine patients including one ineligible patient; however, no polymorphisms were found. The study ceased after interim analysis. In an evaluation of the side effects of irinotecan, patients with UGT1A1*28 and UGT1A1*6 polymorphisms had a higher tendency to experience febrile neutropenia than wild type (25% and 32% vs. 14%). Incidences of grade 3/4 leukopenia and neutropenia were significantly higher in patients with UGT1A1*28 polymorphisms compared with wild type (75% vs. 32%, P = 0.049; 75% vs. 36%, P = 0.039, respectively).
  
  
  CONCLUSIONS
  Our prospective study did not locate the UGT1A1*27 polymorphism, suggesting that UGT1A1*27 does not significantly predict severe irinotecan toxicity in cancer patients.
authors.affiliation: Clinical Oncology Center, Nagasaki University Hospital Nagasaki Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Fukuda
authors.affiliation: Department of Respiratory Medicine Sendai Medical Association Hospital Kagoshima Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Suetsugu
authors.affiliation: Division of Respiratory Diseases, Department of Internal Medicine Japanese Red Cross Nagasaki Genbaku Hospital Nagasaki Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Shimada
authors.affiliation: Division of Respiratory Diseases, Department of Internal Medicine Japanese Red Cross Nagasaki Genbaku Hospital Nagasaki Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kitazaki
authors.affiliation: Division of Respiratory Diseases, Department of Internal Medicine Japanese Red Cross Nagasaki Genbaku Hospital Nagasaki Japan.
authors.forename: Kohji
authors.initials: K
authors.lastname: Hashiguchi
authors.affiliation: Department of Research and Development of Next Generation Medicine Kyusyu University Fukuoka Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Kishimoto
authors.affiliation: Graduate School of Medical Sciences, Research Institute for Disease of the Chest Kyusyu University Fukuoka Japan.
authors.forename: Taishi
authors.initials: T
authors.lastname: Harada
authors.affiliation: Department of Thoracic Oncology National Kyusyu Cancer Center Fukuoka Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Seto
authors.affiliation: Department of Respiratory Oncology Medicine Iizuka Hospital Fukuoka Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ebi
authors.affiliation: Department of Pulmonary Medicine Kyoto Prefectual University of Medicine Kyoto Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Takayama
authors.affiliation: Department of Thoracic and Breast Surgery Oita University Faculty of Medicine Oita Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugio
authors.affiliation: Department of Respiratory Medicine Kumamoto Regional Medical Center Kumamoto Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Semba
authors.affiliation: Graduate School of Medical Sciences, Research Institute for Disease of the Chest Kyusyu University Fukuoka Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakanishi
authors.affiliation: Clinical Research Institute, National Kyusyu Cancer Center Fukuoka Japan.
authors.forename: Yukito
authors.initials: Y
authors.lastname: Ichinose
keywords: Gene polymorphism; UGT1A1; irinotecan; lung cancer; prospective