title: Multicenter phase II trial of dose-fractionated irinotecan in patients with advanced colorectal cancer failing oxaliplatin-based first-line combination chemotherapy.
abstract: BACKGROUND
  A multicenter phase II trial was initiated to investigate the efficacy and tolerance of a dose-fractionated administration schedule of irinotecan in patients with advanced colorectal cancer pre-treated with fluoropyrimidine/ oxaliplatin-based first-line combination chemotherapy.
  
  
  METHODS
  38 patients with metastatic colorectal cancer, who progressed while receiving or within six months after withholding systemic chemotherapy with oxaliplatin in combination with 5-fluorouracil/leucovorin or the specific thymidilate synthase inhibitor raltitrexed were enrolled in this study. Treatment consisted of irinotecan 175 mg/m2 given on days 1 and 10. Courses were repeated every three weeks for a total of six courses unless prior evidence of progressive disease.
  
  
  RESULTS
  The overall objective response rate was 21% for all 38 patients (95% confidence interval (95% CI): 9.6% to 37.4%). Stable disease was noted in 19 patients (50%), whereas the tumour progressed in 11 (29%). The median progression-free survival was 4.8 months (range 1.5 to 10.5). After a median follow-up time of 10 months, 21 patients (55%) are still alive. Treatment was fairly well tolerated with only 9 of 38 patients (24%) experiencing grade 3 or 4 neutropenia. Similarly, nonhaematologic adverse reactions were generally mild; grade 3 toxicities included late-onset diarrhoea in 2 (5%), alopecia in 5 (13%), and infection in 1 case (3%), respectively.
  
  
  CONCLUSIONS
  Our data suggest that this dose-fractionated irinotecan monotherapy schedule has substantial antitumour activity in patients with flupropyrimidine/oxaliplatin-based pre-treated colorectal cancer. Because of its favourable toxicity profile when compared to previous experiences with the European standard schedule of 350 mg/m2 every three weeks, further evaluation of this modified regimen seems warranted.
authors.affiliation: Department of Internal Medicine I, Vienna University Medical School, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Ulrich-Pur
authors.forename: G V
authors.initials: GV
authors.lastname: Kornek
authors.forename: W
authors.initials: W
authors.lastname: Fiebiger
authors.forename: C
authors.initials: C
authors.lastname: Gedlicka
authors.forename: M
authors.initials: M
authors.lastname: Raderer
authors.forename: A
authors.initials: A
authors.lastname: Lenauer
authors.forename: D
authors.initials: D
authors.lastname: Depisch
authors.forename: F
authors.initials: F
authors.lastname: Lang
authors.forename: J
authors.initials: J
authors.lastname: Pidlich
authors.forename: W
authors.initials: W
authors.lastname: Scheithauer
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin