Cancer Chemotherapy and Pharmacology

, Volume 55, Issue 3, pp 263–270

Phase I study of an oral formulation of irinotecan administered daily for 14 days every 3 weeks in patients with advanced solid tumours

Authors

  • Nadja E. Schoemaker
    • Department of Medical Oncology, The Netherlands Cancer InstituteAntoni van Leeuwenhoek Hospital
    • Department of Medical Oncology, The Netherlands Cancer InstituteAntoni van Leeuwenhoek Hospital
    • Department of Pharmacy and Pharmacology, The Netherlands Cancer InstituteSlotervaart Hospital
  • Wim W. Ten Bokkel Huinink
    • Department of Medical Oncology, The Netherlands Cancer InstituteAntoni van Leeuwenhoek Hospital
  • Patricia Lefebvre
    • Aventis Pharma
  • Jos H. Beijnen
    • Department of Pharmacy and Pharmacology, The Netherlands Cancer InstituteSlotervaart Hospital
    • Division of Drug Toxicology, Faculty of PharmacyUtrecht University
  • Sylvie Assadourian
    • Aventis Pharma
  • Ger-Jan Sanderink
    • Division of Drug Toxicology, Faculty of PharmacyUtrecht University
  • Jan H. M. Schellens
    • Department of Medical Oncology, The Netherlands Cancer InstituteAntoni van Leeuwenhoek Hospital
    • Division of Drug Toxicology, Faculty of PharmacyUtrecht University
Original Article

DOI: 10.1007/s00280-004-0874-2

Cite this article as:
Schoemaker, N.E., Kuppens, I.E.L.M., Huinink, W.W.T.B. et al. Cancer Chemother Pharmacol (2005) 55: 263. doi:10.1007/s00280-004-0874-2

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.

Keywords

IrinotecanCPT-11SN-38OralPharmacokineticsPhase I

Copyright information

© Springer-Verlag 2004