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

  • Nadja E. Schoemaker
  • I. E. L. M. Kuppens
  • Wim W. Ten Bokkel Huinink
  • Patricia Lefebvre
  • Jos H. Beijnen
  • Sylvie Assadourian
  • Ger-Jan Sanderink
  • Jan H. M. Schellens
Original Article


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.


Irinotecan CPT-11 SN-38 Oral Pharmacokinetics Phase I 


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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Nadja E. Schoemaker
    • 1
  • I. E. L. M. Kuppens
    • 1
    • 2
  • Wim W. Ten Bokkel Huinink
    • 1
  • Patricia Lefebvre
    • 3
  • Jos H. Beijnen
    • 2
    • 4
  • Sylvie Assadourian
    • 3
  • Ger-Jan Sanderink
    • 4
  • Jan H. M. Schellens
    • 1
    • 4
  1. 1.Department of Medical Oncology, The Netherlands Cancer InstituteAntoni van Leeuwenhoek HospitalAmsterdamThe Netherlands
  2. 2.Department of Pharmacy and Pharmacology, The Netherlands Cancer InstituteSlotervaart HospitalAmsterdamThe Netherlands
  3. 3.Aventis PharmaAntony cedexFrance
  4. 4.Division of Drug Toxicology, Faculty of PharmacyUtrecht UniversityUtrechtThe Netherlands

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