title: A randomised phase II multicentre trial of irinotecan (CPT-11) using four different schedules in patients with metastatic colorectal cancer.
abstract: The purpose of this phase II trial was to compare the efficacy, safety and pharmacokinetics of four irinotecan schedules for the treatment of metastatic colorectal cancer. In total, 174 5-fluorouracil pretreated patients were randomised to: arm A (n=41), 350 mg m(-2) irinotecan as a 90-min i.v. infusion q3 weeks; arm B (n=38), 125 mg m(-2) irinotecan as a 90-min i.v. infusion weekly x 4 weeks q6 weeks; arm C (n=46), 250 mg m(-2) irinotecan as a 90-min i.v. infusion q2 weeks; or arm D (n=49), 10 mg m(-2) day(-1) irinotecan as a 14-day continuous infusion q3 weeks. No significant differences in efficacy across the four arms were observed, although a shorter time to treatment failure was noted for arm D (1.7 months; P=0.02). Overall response rates were in the range 5-11%. Secondary end points included median survival (6.4-9.4 months), and time to progression (2.7-3.8 months) and treatment failure (1.7-3.2 months). Similarly, there were no significant differences in the incidence of grade 3-4 toxicities, although the toxicity profile between arms A, B, and C and D did differ. Generally, significantly less haematologic toxicity, alopecia and cholinergic syndrome were observed in arm D; however, there was a trend for increased gastrointestinal toxicity. Irinotecan is an effective and safe second-line treatment for colorectal cancer. The schedules examined yielded equivalent results, indicating that there is no advantage of the prolonged vs short infusion schedules.
authors.affiliation: Antoni van Leeuwenhoek Hospital/The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: N E
authors.initials: NE
authors.lastname: Schoemaker
authors.forename: I E L M
authors.initials: IE
authors.lastname: Kuppens
authors.forename: V
authors.initials: V
authors.lastname: Moiseyenko
authors.forename: B
authors.initials: B
authors.lastname: Glimelius
authors.forename: M
authors.initials: M
authors.lastname: Kjaer
authors.forename: H
authors.initials: H
authors.lastname: Starkhammer
authors.forename: D J
authors.initials: DJ
authors.lastname: Richel
authors.forename: R
authors.initials: R
authors.lastname: Smaaland
authors.forename: K
authors.initials: K
authors.lastname: Bertelsen
authors.forename: J P
authors.initials: JP
authors.lastname: Poulsen
authors.forename: E
authors.initials: E
authors.lastname: Voznyi
authors.forename: J
authors.initials: J
authors.lastname: Norum
authors.forename: D
authors.initials: D
authors.lastname: Fennelly
authors.forename: K M
authors.initials: KM
authors.lastname: Tveit
authors.forename: A
authors.initials: A
authors.lastname: Garin
authors.forename: G
authors.initials: G
authors.lastname: Gruia
authors.forename: A
authors.initials: A
authors.lastname: Mourier
authors.forename: D
authors.initials: D
authors.lastname: Sibaud
authors.forename: P
authors.initials: P
authors.lastname: Lefebvre
authors.forename: J H
authors.initials: JH
authors.lastname: Beijnen
authors.forename: J H M
authors.initials: JH
authors.lastname: Schellens
authors.forename: W W
authors.initials: WW
authors.lastname: ten Bokkel Huinink
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000293:Adolescent; D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D059004:Topoisomerase I Inhibitors; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D059004:Topoisomerase I Inhibitors; D000077146:Irinotecan; D002166:Camptothecin