title: Phase II and UGT1A1 genotype study of irinotecan dose escalation as salvage therapy for advanced gastric cancer.
abstract: BACKGROUND
  To assess the efficacy and safety of individualised dose optimisation of irinotecan monotherapy as salvage treatment for advanced gastric cancer (AGC).
  
  
  METHODS
  A total of 43 patients were enrolled. Intravenous irinotecan (350 mg m(-2)) was administered every 3 weeks. The dose was increased (425 mg m(-2) and 500 mg m(-2)) or decreased (250 mg m(-2)) depending on patient tolerance. UGT1A1 genotypes were determined by direct sequencing of genomic DNA extracted from peripheral blood.
  
  
  RESULTS
  A total of 183 cycles of irinotecan were administered, with a median of four cycles per patient. The overall response rate was 9.3%, and the disease control rate was 62.8%. Median time to disease progression was 2.8 months, and median overall survival was 8.0 months. Grade 3-4 neutropenia was the most common toxicity (53.5%), and febrile neutropenia was the least common toxicity (4.6%). Compared with defective allele groups, UGT1A1 *1/*1 was associated with a lower incidence of grade 3-4 neutropenia during the first cycle (P=0.018).
  
  
  CONCLUSIONS
  Individualised irinotecan dose escalation based on patient tolerance was not associated with increased toxicity and shows modest activity as salvage chemotherapy for AGC. The role of UGT1A1 genotype in clinical toxicity requires further evaluation.
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea.
authors.forename: J-C
authors.initials: JC
authors.lastname: Jo
authors.forename: J-L
authors.initials: JL
authors.lastname: Lee
authors.forename: M-H
authors.initials: MH
authors.lastname: Ryu
authors.forename: H M
authors.initials: HM
authors.lastname: Chang
authors.forename: M
authors.initials: M
authors.lastname: Kim
authors.forename: H J
authors.initials: HJ
authors.lastname: Lee
authors.forename: H-S
authors.initials: HS
authors.lastname: Kim
authors.forename: J-G
authors.initials: JG
authors.lastname: Shin
authors.forename: T-W
authors.initials: TW
authors.lastname: Kim
authors.forename: Y-K
authors.initials: YK
authors.lastname: Kang
mesh_terms: D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D016879:Salvage Therapy; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D000099148:UGT1A1 Enzyme
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D000099148:UGT1A1 Enzyme