title: CPT-11 as a second-line treatment for patients with advanced/metastatic gastric cancer who failed S-1 (CCOG0702).
abstract: BACKGROUND
  In Japan, CPT-11 is often used to treat unresectable gastric cancer in the second-line setting. However, evidence regarding benefit of second-line chemotherapy remains sparse, especially after failing S-1.
  
  
  METHODS
  A phase II study to evaluate the efficacy and safety of weekly administration of CPT-11 at a dose of 100 mg/m(2) after failing a S-1-containing first-line treatment was planned with response rate as a primary end point. UGT1A1*6, *27, and *28 genotyping were performed in all cases, and those found to have either homozygous for *28, homozygous for *6, heterozygous for both *6 and *28, and heterozygous for *27 were rendered ineligible for the phase II trial.
  
  
  RESULTS
  Two patients of homozygous for *28, two patients of homozygous for *6, and one patient of heterozygous for *27 were found among 39 recruited patients. The median number of courses delivered was 3 courses. The overall response rate was 15.4 % and disease control rate was 65.4 %. The median time to treatment failure was 87.5 days and median overall survival was 268 days. Twenty-two (73 %) of 30 valuable patients experienced protocol-specified skip of treatment and 8 (30 %) of patients could continue treatment with dose reduction. ≥G3 neutropenia was found in 30 % and ≥G3 anorexia and diarrhea were found in 23 and 17 %, respectively.
  
  
  CONCLUSIONS
  Weekly CPT-11 at 100 mg/m(2) showed moderate response among gastric cancer patients who were refractory to S-1, but the disease control rate seemed meaningful. Even after selection of patients by UGT1A1 polymorphism of *6, *27, and *28, severe toxic events could not be prevented completely.
authors.affiliation: Department of Surgery, Komaki City Hospital, 1-20 Jobushi, Komaki, Aichi, Japan. ymochizuki@ivy.ocn.ne.jp
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Mochizuki
authors.forename: Norifumi
authors.initials: N
authors.lastname: Ohashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kojima
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ishigure
authors.forename: Takashi
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Takehiko
authors.initials: T
authors.lastname: Eguchi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Fujitake
authors.forename: Seiji
authors.initials: S
authors.lastname: Ito
authors.forename: Michitaka
authors.initials: M
authors.lastname: Fujiwara
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kodera
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; 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; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010094:Oxonic Acid / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015996:Survival Rate; D005641:Tegafur / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D000099148:UGT1A1 Enzyme
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin; D004338:Drug Combinations; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D010094:Oxonic Acid; D005641:Tegafur; D000099148:UGT1A1 Enzyme; C079198:S 1 (combination)