title: Phase I study of an oral formulation of irinotecan administered daily for 14 days every 3 weeks in patients with advanced solid tumours.
abstract: A phase I study was conducted with oral irinotecan given daily for 14 days every 3 weeks in 45 patients with solid tumours to establish the maximum tolerated dose (MTD), toxicity, preliminary antitumour response and pharmacokinetics. Irinotecan was administered orally as a powder-filled capsule at doses ranging from 7.5 to 40 mg/m2 per day. Tumours were predominantly colorectal (30) together with 10 other gastrointestinal, 2 breast, 2 small cell lung and 1 ovarian. All but three patients had received prior chemotherapy. The median number of administered cycles was 3 (range 1-19). Gastrointestinal toxicities (grade 3 nausea, grade 3/4 vomiting and diarrhoea) and one incidence of grade 3 asthenia were dose limiting. There were no grade 3/4 haematological toxicities. The MTD was 30 mg/m2 per day. There were two documented partial responses, one in a patient with cancer of the small intestine and the other in a patient with colon cancer. Stable disease was seen in 16 patients (35.5%). Peak concentrations of irinotecan and metabolite SN-38 were reached within 2.0-2.4 h. The metabolic ratio of SN-38 AUC to irinotecan AUC was 0.17+/-0.10 (mean+/-SD). The dose recommended for phase II studies is 30 mg/m2 per day administered daily for 14 days every 3 weeks.
authors.affiliation: Department of Medical Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
authors.forename: Nadja E
authors.initials: NE
authors.lastname: Schoemaker
authors.forename: I E L M
authors.initials: IE
authors.lastname: Kuppens
authors.forename: Wim W Ten Bokkel
authors.initials: WW
authors.lastname: Huinink
authors.forename: Patricia
authors.initials: P
authors.lastname: Lefebvre
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
authors.forename: Sylvie
authors.initials: S
authors.lastname: Assadourian
authors.forename: Ger-Jan
authors.initials: GJ
authors.lastname: Sanderink
authors.forename: Jan H M
authors.initials: JH
authors.lastname: Schellens
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D002166:Camptothecin / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D041981:Gastrointestinal Tract / Q000187:drug effects; D006801:Humans; D000077146:Irinotecan; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D059004:Topoisomerase I Inhibitors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors; D000077146:Irinotecan; D002166:Camptothecin