药代动力学
伊立替康
医学
肝动脉灌注
中性粒细胞减少症
序号38
胃肠病学
化疗
药理学
内科学
结直肠癌
癌症
作者
J.M.G.H. van Riel,C.J. van Groeningen,Mark A. Kedde,Helen Gall,Johanna M. A. Leisink,G. Gruia,H.M. Pinedo,W.J.F. van der Vijgh,Giuseppe Giaccone
出处
期刊:PubMed
日期:2002-02-01
卷期号:8 (2): 405-12
被引量:24
摘要
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.
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