Details

Autor(en) / Beteiligte

• VAN RIEL, Johanna M. G. H
• VAN GROENINGEN, Cees J
• KEDDE, Mark A
• GALL, Helen
• LEISINK, Johanna M. A
• GRUIA, Gabriella
• PINEDO, Herbert M
• VAN DER VIJGH, Wim J. F
• GIACCONE, Giuseppe

Titel

Continuous administration of irinotecan by hepatic arterial infusion: A Phase I and pharmacokinetic study

Ist Teil von

• Clinical cancer research, 2002-02, Vol.8 (2), p.405-412

Ort / Verlag

Philadelphia, PA: American Association for Cancer Research

Erscheinungsjahr

2002

Quelle

MEDLINE

Beschreibungen/Notizen

• The main advantage of administering chemotherapy by means of hepatic arterial infusion (HAI) is the achievement of a high concentration of the drug in the liver. Irinotecan (CPT-11) is an active agent for the treatment of advanced colorectal cancer and other tumor types, which frequently metastasize in the liver. We performed a Phase I and pharmacokinetic study to investigate CPT-11 by hepatic arterial administration in patients with liver metastases. Patients with liver metastases received CPT-11 at doses ranging from 15 to 25 mg/m(2)/day for 5 days every 3 weeks by continuous HAI. All of the patients also received one cycle CPT-11 i.v. Primary end points of the study were to define the maximum tolerated dose (MTD) of hepatic arterial CPT-11 and to study its pharmacokinetics. Twenty patients were included. The MTD was 25 mg/m(2)/day and the dose-limiting toxicities were neutropenia and diarrhea. The metabolic ratio was significantly increased with HAI compared with i.v. administration (P = 0.015). The steady-state concentrations of total CPT-11 and CPT-11 carboxylate and lactone were all lower than those during i.v. infusion (P = 0.008, 0.013, and 0.004, respectively), whereas the levels of total SN-38, and SN-38 carboxylate, lactone, and glucuronide were similar. The total body clearance of CPT-11 was significantly higher with HAI (P = 0.008). The MTD of CPT-11 given by hepatic 5-day continuous infusion was 25 mg/m(2)/day. HAI of CPT-11 resulted in a higher metabolic ratio because of increased elimination of CPT-11. We recommend 20 mg/m(2)/day for additional Phase II studies.