title: Phase II and UGT1A1 Polymorphism Study of Two Different Irinotecan Dosages Combined with Cisplatin as First-Line Therapy for Advanced Gastric Cancer.
abstract: BACKGROUND
  We investigated the efficacy and safety of biweekly irinotecan and cisplatin (IP) as first-line treatment in advanced gastric cancer patients.
  
  
  METHODS
  Irinotecan 125 mg/m2 on day 1 and cisplatin 60 mg/m2 on day 2 were administrated every 14 days. UGT1A1*28/*6 and toxicities were analyzed.
  
  
  RESULTS
  Forty-one eligible patients were enrolled. Fifteen patients, who were defined as the high-dose group, received starting doses of irinotecan 125 mg/m2. Twenty-six patients, who were defined as the low-dose group, received starting doses of irinotecan 80 mg/m2 and cisplatin 50 mg/m2. The response rate was 53.3% in the irinotecan high-dose group and 53.8% in the irinotecan low-dose group. The most common grade 3/4 toxicity was neutropenia (68.3%). No significant difference in grade 3/4 neutropenia was found between patients with the wild-type genotype and those with variant genotypes for UGT1A1*28 or UGT1A1*6.
  
  
  CONCLUSIONS
  The combination of biweekly irinotecan 80 mg/m2 and cisplatin 50 mg/m2 was active and tolerable. The role of the UGT1A1 genotype in clinical toxicity of an IP regimen requires further investigation.
authors.forename: Wenna
authors.initials: W
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Tao
authors.forename: Xiao
authors.initials: X
authors.lastname: Lyu
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.forename: Dawei
authors.initials: D
authors.lastname: Wu
authors.forename: Yantao
authors.initials: Y
authors.lastname: Tian
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use*; D054796:Drug Dosage Calculations; D004359:Drug Therapy, Combination; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006402:Hematologic Diseases / Q000209:etiology; D006801:Humans; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D014057:Tomography, X-Ray Computed; D000099148:UGT1A1 Enzyme
chemical_list: D000970:Antineoplastic Agents; D002166:Camptothecin; D002945:Cisplatin; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D000099148:UGT1A1 Enzyme