title: A randomized phase II trial of capecitabine and two different schedules of irinotecan in first-line treatment of metastatic colorectal cancer: efficacy, quality-of-life and toxicity.
abstract: BACKGROUND
  To determine the efficacy, impact on quality-of-life (QoL) and tolerability of two different irinotecan administration schedules in combination with capecitabine as first-line treatment of metastatic colorectal cancer.
  
  
  METHODS
  We carried out a randomized phase II trial to select one of the following treatment regimens for further investigation: weekly irinotecan at a dose of 70 mg/m(2) days 1, 8, 15, 22, 29 (arm A) or 3-weekly irinotecan at a dose of 300/240 mg/m(2) day 1 and days 22 (arm B) in combination with capecitabine 1000 mg/m(2) twice daily days 1-14 and days 22-35 every 6 weeks.
  
  
  RESULTS
  Seventy-five patients with good performance status entered the trial. The two arms were well balanced for relevant patient and disease characteristics. The most frequent toxic effects were grade 3/4 diarrhea (arm A: 34%, B: 19%), grade 3/4 neutropenia (A: 5%, B: 19%) and grade 2/3 alopecia (A: 26%, B: 65%). Other grade 3/4 toxic effects were rare (<5%). Response rates were 34% [95% confidence interval (CI) 20% to 51%] in arm A and 35% (95% CI: 20% to 53%) in arm B. Median time to progression was 6.9 (4.6-10.1) and 9.2 (7.9-11.5) months and median overall survival was 17.4 (12.6-23.0+) and 24.7 (16.3-26.4+) months. Patients with an objective tumor response reported better physical well-being (P < 0.01), mood (P < 0.05), functional performance (P < 0.05) and less effort to cope (P < 0.05) compared with the non-responders and stable disease patients.
  
  
  CONCLUSIONS
  The primary end point of this study was the objective response rate and based on the statistical design of the trial, the 3-weekly irinotecan schedule was selected over weekly irinotecan administration. The 3-weekly irinotecan schedule also seemed advantageous in terms of grade 3/4 diarrhea, time to progression, overall survival and patient convenience, but the study was not designed to detect differences in these parameters. In addition, tumor response was shown to have a beneficial effect on QoL indicators.
authors.affiliation: Institute of Medical Oncology, Inselspital, 3101 Berne, Switzerland. markus.borner@insel.ch
authors.forename: M M
authors.initials: MM
authors.lastname: Borner
authors.forename: J
authors.initials: J
authors.lastname: Bernhard
authors.forename: D
authors.initials: D
authors.lastname: Dietrich
authors.forename: R
authors.initials: R
authors.lastname: Popescu
authors.forename: M
authors.initials: M
authors.lastname: Wernli
authors.forename: P
authors.initials: P
authors.lastname: Saletti
authors.forename: D
authors.initials: D
authors.lastname: Rauch
authors.forename: R
authors.initials: R
authors.lastname: Herrmann
authors.forename: D
authors.initials: D
authors.lastname: Koeberle
authors.forename: H
authors.initials: H
authors.lastname: Honegger
authors.forename: P
authors.initials: P
authors.lastname: Brauchli
authors.forename: D
authors.initials: D
authors.lastname: Lanz
authors.forename: A D
authors.initials: AD
authors.lastname: Roth
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / 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*; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D003841:Deoxycytidine; D000069287:Capecitabine; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin