title: Phase I study of irinotecan for previously treated lung cancer patients with the UGT1A1*28 or *6 polymorphism: Results of the Lung Oncology Group in Kyushu (LOGIK1004A).
abstract: BACKGROUND
  Various polymorphisms have been detected in the UDP-glucuronosyltransferase 1A ( UGT1A ) gene, and UGT1A1 *28 and UGT1A1 *6 have important effects on the pharmacokinetics of irinotecan and the risk of severe toxicities during irinotecan therapy. This study was conducted to determine the maximum tolerated dose (MTD) of irinotecan chemotherapy according to the UGT1A1 genotype in previously treated lung cancer patients with the UGT1A1 *28 or UGT1A1 *6 polymorphism.
  
  
  METHODS
  The eligibility criteria were as follows: lung cancer patients that had previously been treated with anticancer agents other than irinotecan, possessed the UGT1A1 *28 or UGT1A1 *6 polymorphism (group A included *28/*28, *6/*6, and *28/*6, and group B included *28 /- and *6 /-), were aged ≤75 years old, had a performance score of 0-1, and exhibited adequate bone marrow function. The patients were scheduled to receive irinotecan on days 1, 8, 15, 22, 29, and 36.
  
  
  RESULTS
  Four patients were enrolled in this trial. Two patients were determined to be ineligible. The remaining two patients, who belonged to group B, received an initial irinotecan dose of 60 mg/m2, but did not complete the planned treatment because of diarrhea and leukopenia. Thus, in group B patients, 60 mg/m2was considered to be the MTD of irinotecan. The study was terminated in group A because of poor case recruitment.
  
  
  CONCLUSIONS
  The MTD of irinotecan for previously treated lung cancer patients that are heterozygous for the UGT1A1 * 28 or UGT1A1 * 6 gene polymorphism is 60 mg/m2.
authors.affiliation: Clinical Oncology Center, Nagasaki University Hospital, Nagasaki, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Fukuda
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: Department of Medicine, National Hospital Organization Nagasaki Medical Center, Nagasaki, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Nagashima
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 Respiratory Oncology Medicine, Iizuka Hospital, Fukuoka, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ebi
authors.affiliation: Department of Pulmonary Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Takayama
authors.affiliation: Research Institute for Disease of the Chest, Graduate School of Medical Sciences, Kyusyu University, Fukuoka, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakanishi
authors.affiliation: Department of Respiratory Medicine, Kumamoto Regional Medical Center, Kumamoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Semba
authors.affiliation: Research Institute for Disease of the Chest, Graduate School of Medical Sciences, 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: Research Institute for Disease of the Chest, Graduate School of Medical Sciences, Kyusyu University, Fukuoka, Japan.
authors.forename: Isamu
authors.initials: I
authors.lastname: Okamoto
authors.affiliation: Clinical Research Institute, National Kyusyu Cancer Center, Fukuoka, Japan.
authors.forename: Yukito
authors.initials: Y
authors.lastname: Ichinose
authors.affiliation: Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine, Oita, Japan.|Lung Oncology Group in Kyusyu, Fukuoka, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugio
mesh_terms: D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome; D000099148:UGT1A1 Enzyme
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D000099148:UGT1A1 Enzyme
keywords: 
  
  UGT1A
  
  1
  ; 
  Gene polymorphism; irinotecan; lung cancer; phase I
  