title: Phase III comparison of two irinotecan dosing regimens in second-line therapy of metastatic colorectal cancer.
abstract: OBJECTIVE
  Randomized trials in fluorouracil (FU)-refractory colorectal cancer demonstrate significant survival advantages for patients receiving irinotecan. We prospectively compared the efficacy and tolerability of two irinotecan regimens (once a week for 4 weeks followed by a 2-week rest period [weekly] v once every 3 weeks) in such patients.
  
  
  METHODS
  This multicenter, open-label, phase III study randomly assigned patients in a 1:2 ratio to irinotecan given either weekly (125 mg/m(2)) or once every 3 weeks (350 mg/m(2), or 300 mg/m(2) in patients who were >/= 70 years of age, who had Eastern Cooperative Oncology Group performance status equal to 2, or who had prior pelvic irradiation).
  
  
  RESULTS
  With median follow-up of 15.8 months, there was no significant difference in 1-year survival (46% v 41%, respectively; P =.42), median survival (9.9 v 9.9 months, respectively; P =.43), or median time to progression (4.0 v 3.0 months, respectively; P =.54) between the two regimens. Grade 3/4 diarrhea occurred in 36% of patients treated weekly and in 19% of those treated once every 3 weeks (P =.002). Grade 3/4 neutropenia occurred in 29% of patients treated weekly and 34% of those treated once every 3 weeks (P =.35). Treatment-related mortality occurred in five patients (5.3%) receiving irinotecan weekly and three patients (1.6%) given therapy once every 3 weeks (P =.12). Global quality of life was not statistically different between treatment groups.
  
  
  CONCLUSIONS
  Irinotecan schedules of weekly and of once every 3 weeks demonstrated similar efficacy and quality of life in patients with FU-refractory, metastatic colorectal cancer. The regimen of once every 3 weeks was associated with a significantly lower incidence of severe diarrhea.
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA 02115, USA. charles_fuchs@dfci.harvard.edu
authors.forename: Charles S
authors.initials: CS
authors.lastname: Fuchs
authors.forename: Melvin R
authors.initials: MR
authors.lastname: Moore
authors.forename: Graydon
authors.initials: G
authors.lastname: Harker
authors.forename: Luis
authors.initials: L
authors.lastname: Villa
authors.forename: David
authors.initials: D
authors.lastname: Rinaldi
authors.forename: J Randolph
authors.initials: JR
authors.lastname: Hecht
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000627:therapeutic use; D001663:Bilirubin / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis; D002166:Camptothecin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008297:Male; D011446:Prospective Studies; D011788:Quality of Life; D016879:Salvage Therapy; D015996:Survival Rate; D059004:Topoisomerase I Inhibitors; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D059004:Topoisomerase I Inhibitors; D000077146:Irinotecan; D001663:Bilirubin; D002166:Camptothecin