title: Prospective phase II study of FOLFIRI for mCRC in Japan, including the analysis of UGT1A1 28/6 polymorphisms.
abstract: OBJECTIVE
  This is the first phase II study to evaluate the efficacy and tolerability of the first-line FOLFIRI, as well as the influence of uridine diphosphate glucuronosyl transferase 1, family polypeptide A1 gene (UGT1A1) 28/6 polymorphism, in Japanese metastatic colorectal cancer patients.
  
  
  METHODS
  Fifty-two patients were enrolled in this study and were administrated FOLFIRI (irinotecan; 150 mg/m(2)) as first-line chemotherapy. Thirty-nine patients accepted the evaluation of UGT1A1 genotypes. In patients with UGT1A1 28 homozygosity, the starting dose was reduced (100 mg/m(2)) according to the Food and Drug Administration recommendation and our previous phase I study.
  
  
  RESULTS
  After a median follow-up period of 22 months, complete response was achieved in 1.9%, partial response in 38.5 %, stable disease in 51.9% and progressive disease in 3.9%. The overall response rate was 40.4%, the disease control rate was 92.3% and the median overall survival time was 22.3 months. The major toxicity was grade 3-4 neutropenia in 44.2%. There was no definite relation between UGT1A1 28, 6 polymorphisms and toxicity. However, homozygosity for UGT1A1 28 or UGT1A1 6 and double heterozygosity for both UGT1A1 28 and UGT1A1 6 were significantly associated with severe neutropenia in metastatic colorectal cancer patients (P< 0.001).
  
  
  CONCLUSIONS
  FOLFIRI is effective and tolerable for Japanese metastatic colorectal cancer patients. Homozygosity for UGT1A1 28 or 6 and heterozygosity for both UGT1A1 28 and 6 are associated with severe neutropenia.
authors.affiliation: Department of Gastroenterology, Kyoto First Red Cross Hospital, Honmachi 15-749, Higashiyama-ku, Kyoto, Japan. yusuke-okuyama@kyoto1-jrc.org
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Okuyama
authors.forename: Shoichi
authors.initials: S
authors.lastname: Hazama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nozawa
authors.forename: Michiya
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Takahashi
authors.forename: Koshi
authors.initials: K
authors.lastname: Fujikawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kato
authors.forename: Naoki
authors.initials: N
authors.lastname: Nagata
authors.forename: Humihiko
authors.initials: H
authors.lastname: Kimura
authors.forename: Koji
authors.initials: K
authors.lastname: Oba
authors.forename: Junichi
authors.initials: J
authors.lastname: Sakamoto
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Mishima
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D020022:Genetic Predisposition to Disease; D014453:Glucuronosyltransferase / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D000077146:Irinotecan; D007564:Japan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced / Q000175:diagnosis; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012720:Severity of Illness Index; D059004:Topoisomerase I Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D000099148:UGT1A1 Enzyme
chemical_list: D002166:Camptothecin; D005472:Fluorouracil; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D002955:Leucovorin; D059004:Topoisomerase I Inhibitors; D000099148:UGT1A1 Enzyme