title: Regimen selection for first-line FOLFIRI and FOLFOX based on UGT1A1 genotype and physical background is feasible in Japanese patients with advanced colorectal cancer.
abstract: OBJECTIVE
  We examined the feasibility of regimen selection for first-line irinotecan, 5-fluorouracil and leucovorin or oxaliplatin, 5-fluorouracil and leucovorin in Japanese patients with advanced colorectal cancer based on UDP-glucuronosyltransferase 1A1 genotype as well as physical status of patients related to diarrhea.
  
  
  METHODS
  As first-line irinotecan, 5-fluorouracil and leucovorin is a little bit superior to oxaliplatin, 5-fluorouracil and leucovorin with respect to efficacy and toxicity, patients without risk factors of irinotecan-induced toxicity were first assigned to irinotecan, 5-fluorouracil and leucovorin. Patients with UDP-glucuronosyltransferase 1A1 28/ 28, 6/ 6, 28/ 6 or 28/ 27 and those with ascites, peritoneal dissemination or diarrhea first received oxaliplatin, 5-fluorouracil and leucovorin to avoid the irinotecan-induced neutropenia and diarrhea, respectively. We retrospectively evaluated the feasibility of this strategy by assessing toxicity and total progression-free survival in first- and subsequent second-line therapies in all patients studied.
  
  
  RESULTS
  In the first-line irinotecan, 5-fluorouracil and leucovorin (n = 61), Grade 4 neutropenia, febrile neutropenia and Grade 3 diarrhea occurred in 8.2, 3.3 and 3.3% of patients, respectively. In the first-line oxaliplatin, 5-fluorouracil and leucovorin (n = 26), Grade 4 neutropenia, febrile neutropenia, Grade 3 thrombocytopenia and Grade 3 neuropathy were observed in 11.5, 3.8, 3.8 and 7.7% of patients, respectively. In the second-line oxaliplatin, 5-fluorouracil and leucovorin (n = 38), Grade 3 diarrhea occurred in 2.6% of patients. In the second-line irinotecan monotherapy (n = 11), Grade 4 or febrile neutropenia occurred in 18% of patients and Grade 3 diarrhea in 9.1% of patients. In second-line S-1 (n = 9), Grade 3 anemia occurred in 2 patients. Median total progression-free survival in all 87 patients was 11.5 months.
  
  
  CONCLUSIONS
  Present regimen selection strategy would be feasible, since it causes less toxicity and similar efficacy comparing to previous studies. Determination of appropriate reduced dose in the second-line irinotecan monotherapy or other standard second-line therapy for patients with high-risk to irinotecan-induced toxicity might make this strategy more effective.
authors.affiliation: Department of Medical Oncology, International Medical Center-Comprehensive Cancer Center, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1298, Japan.
authors.forename: Hiroo
authors.initials: H
authors.lastname: Ishida
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Fujita
authors.forename: Yuko
authors.initials: Y
authors.lastname: Akiyama
authors.forename: Yu
authors.initials: Y
authors.lastname: Sunakawa
authors.forename: Keishi
authors.initials: K
authors.lastname: Yamashita
authors.forename: Keiko
authors.initials: K
authors.lastname: Mizuno
authors.forename: Keisuke
authors.initials: K
authors.lastname: Miwa
authors.forename: Kaori
authors.initials: K
authors.lastname: Kawara
authors.forename: Wataru
authors.initials: W
authors.lastname: Ichikawa
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ando
authors.forename: Shigehira
authors.initials: S
authors.lastname: Saji
authors.forename: Yasutsuna
authors.initials: Y
authors.lastname: Sasaki
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 / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D003967:Diarrhea / Q000139:chemically induced / Q000209:etiology*; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D012189:Retrospective Studies; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D000099148:UGT1A1 Enzyme
chemical_list: D002166:Camptothecin; D005472:Fluorouracil; D014453:Glucuronosyltransferase; D002955:Leucovorin; D009944:Organoplatinum Compounds; D000099148:UGT1A1 Enzyme