title: Clinical activity and benefit of irinotecan (CPT-11) in patients with colorectal cancer truly resistant to 5-fluorouracil (5-FU).
abstract: The aim of this prospective study was to assess the efficacy, clinical benefit and safety of CPT-11 (irinotecan) in patients with stringently-defined 5-fluorouracil-resistant metastatic colorectal cancer (CRC). 107 patients with documented progression of metastatic CRC during 5-FU were treated with CPT-11 350 mg/m2 once every 3 weeks in a multicentre phase II study. Tumour response and toxicity were assessed using WHO criteria. Changes in performance status (PS), weight and pain were also measured. The WHO response rate was 13/95 (13.7%, 95% CI 7.5% to 22.3%) eligible patients with a median duration of response of 8.5 months (37 weeks, range: 18-53+). There was also a high rate of disease stabilisation (44.2%) with a median duration of 4.8 months. The probability of being free of progression at 4 months was 50%. Median survival from first administration of CPT-11 was 10.4 months or 45 weeks (range: 3-66+ weeks). There was weight stabilisation or gain in 81% (73/90) of patients, a favourable outcome in PS in 91% (82/90) (improvement of WHO PS 2 or stabilisation of PS 0-1), and pain relief in 54% (26/48). There were no toxic deaths. Neutropenia was short-lasting and non-cumulative. Diarrhoea grade > or = 3 occurred in 7% of cycles and 28/107 (26%) of patients. CPT-11 350 mg/m2 once every 3 weeks has an encouraging degree of activity in progressive metastatic CRC truly resistant to 5-FU with a relatively high rate of tumour growth control translated into clinical benefit. The toxicity profile of CPT-11 is becoming better understood and has been considerably improved.
authors.affiliation: University Hospital Gasthuisberg, Department of Internal Medicine, Leuven, Belgium. eric.vancutsem@uz.kuleuven.ac.be
authors.forename: E
authors.initials: E
authors.lastname: Van Cutsem
authors.forename: D
authors.initials: D
authors.lastname: Cunningham
authors.forename: W W
authors.initials: WW
authors.lastname: Ten Bokkel Huinink
authors.forename: C J
authors.initials: CJ
authors.lastname: Punt
authors.forename: C G
authors.initials: CG
authors.lastname: Alexopoulos
authors.forename: L
authors.initials: L
authors.lastname: Dirix
authors.forename: M
authors.initials: M
authors.lastname: Symann
authors.forename: G H
authors.initials: GH
authors.lastname: Blijham
authors.forename: P
authors.initials: P
authors.lastname: Cholet
authors.forename: G
authors.initials: G
authors.lastname: Fillet
authors.forename: C
authors.initials: C
authors.lastname: Van Groeningen
authors.forename: J M
authors.initials: JM
authors.lastname: Vannetzel
authors.forename: F
authors.initials: F
authors.lastname: Levi
authors.forename: G
authors.initials: G
authors.lastname: Panagos
authors.forename: C
authors.initials: C
authors.lastname: Unger
authors.forename: J
authors.initials: J
authors.lastname: Wils
authors.forename: C
authors.initials: C
authors.lastname: Cote
authors.forename: C
authors.initials: C
authors.lastname: Blanc
authors.forename: P
authors.initials: P
authors.lastname: Hérait
authors.forename: H
authors.initials: H
authors.lastname: Bleiberg
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011788:Quality of Life; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin