title: Prospective phase II trial of second-line FOLFIRI in patients with advanced colorectal cancer including analysis of UGT1A1 polymorphisms: FLIGHT 2 study.
abstract: OBJECTIVE
  This is a multicenter phase II study to assess the efficacy and toxicity of FOLFIRI treatment agents in full and the influence of UGT1A1*28 polymorphism in Japanese patients with advanced/metastatic colorectal cancer (mCRC).
  
  
  METHODS
  Fifty patients with mCRC participated in this study. Treatment consisted of FOLFIRI (irinotecan; 150 mg/m(2)) as second-line chemotherapy; 34 patients consented to the evaluation of UGT1A1 genotype.
  
  
  RESULTS
  The overall response rate was 12% for all 50 evaluable patients; 31 patients (62.0%) had stable disease, and only in 12 (24.0%) did disease progress. The median progression-free survival was 5.8 months. The tolerance treatment was acceptable, with only 15 out of 50 patients (30%) experiencing grade 3/4 neutropenia, and grade 4 thrombocytopenia was observed in only one case. Grade 3 non-hematological adverse reactions included stomatitis in three, diarrhea in one, and a clinically insignificant increase in serum alkaline phosphatases in one patient, respectively. There was no definite relation between the UGT1A1*28 polymorphism and toxicity.
  
  
  CONCLUSIONS
  Standard FOLFIRI regimen can be administered to Japanese patients. The results showed good tolerability and efficacy for second-line FOLFIRI, provided that evaluation of UGT1A1 polymorphism is properly implemented before the start of the chemotherapy.
authors.affiliation: Department of Surgery, Kitakyushu General Hospital, 5-10-10 Yugawa, Kokuraminami-ku, Kitakyushu 800-0295, Japan. n-nagata@kitakyu-hp.or.jp.
authors.forename: Keiji
authors.initials: K
authors.lastname: Hirata
authors.forename: Naoki
authors.initials: N
authors.lastname: Nagata
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kato
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Okuyama
authors.forename: Hideaki
authors.initials: H
authors.lastname: Andoh
authors.forename: Kenichi
authors.initials: K
authors.lastname: Takahashi
authors.forename: Koji
authors.initials: K
authors.lastname: Oba
authors.forename: Junichi
authors.initials: J
authors.lastname: Sakamoto
authors.forename: Shoichi
authors.initials: S
authors.lastname: Hazama
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Mishima
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D005500:Follow-Up Studies; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011446:Prospective Studies; D015996:Survival Rate; D000099148:UGT1A1 Enzyme
chemical_list: D002166:Camptothecin; D005472:Fluorouracil; D014453:Glucuronosyltransferase; D002955:Leucovorin; D000099148:UGT1A1 Enzyme
keywords: Chemotherapy; FOLFIRI regimen; UGT1A1; metastatic colorectal cancer; phase II study