title: Alternative dosing schedules for irinotecan.
abstract: Most of the clinical experience with irinotecan (CPT-11 [Camptosar]) has been with either a weekly or an every-3-week schedule. Recent phase I trials have explored new routes and schedules of administration. One approach attempts to maximize dose frequency and intensity by giving irinotecan every 2 weeks. A phase I trial of this approach is now complete and has led to a phase II trial in patients with recurrent colorectal cancer. Data suggest that smaller doses of a topoisomerase I inhibitor administered repeatedly may result in greater antitumor activity than large doses administered intermittently. A phase I trial has been performed in adults in which irinotecan was administered daily for 5 consecutive days, followed by 2 days off, for 2 weeks out of 3. Similar trials are under way in children. Oral administration, another strategy that has undergone phase I testing, has several theoretical advantages:(1) The acidic pH of the stomach favors maintenance of irinotecan in the active lactone ring form. (2) Irinotecan is more rapidly and extensively converted to SN-38 by tissue carboxylesterases found in high concentrations in the gut and liver. (3) Low doses can be delivered over a protracted period. (4) The oral route enhances patient convenience. These alternative dosing schedules may facilitate integration of irinotecan into combination chemotherapy and combined-modality treatment regimens.
authors.affiliation: Division of Medical Oncology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Rothenberg
authors.forename: J G
authors.initials: JG
authors.lastname: Kuhn
authors.forename: L J
authors.initials: LJ
authors.lastname: Schaaf
authors.forename: R L
authors.initials: RL
authors.lastname: Drengler
authors.forename: S G
authors.initials: SG
authors.lastname: Eckhardt
authors.forename: M A
authors.initials: MA
authors.lastname: Villalona-Calero
authors.forename: L
authors.initials: L
authors.lastname: Hammond
authors.forename: L L
authors.initials: LL
authors.lastname: Miller
authors.forename: R G
authors.initials: RG
authors.lastname: Petit
authors.forename: E K
authors.initials: EK
authors.lastname: Rowinsky
authors.forename: D D
authors.initials: DD
authors.lastname: Von Hoff
mesh_terms: D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D000077146:Irinotecan
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin