Journal of Clinical Oncology, 2005 ASCO Annual Meeting Proceedings.
Vol 23, No 16S (June 1 Supplement), 2005: 2073
© 2005 American Society of Clinical Oncology

This Article Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Yin, D. Articles by Sharma, A. Search for Related Content PubMed Articles by Yin, D. Articles by Sharma, A.

Abstract

Pharmacokinetics (PK) of edotecarin (J-107088), a topoisomerase I inhibitor, in patients with metastatic breast cancer (mBC) or glioblastoma multiforme (GBM)

Pfizer Inc., New London, CT

2073

Background: Edotecarin is an indolocarbazole topoisomerase I inhibitor currently under clinical development for cancer treatment. Objectives of the present PK investigations were to fully characterize the PK of edotecarin at the previously defined maximum tolerated dose (MTD, 13 mg/ m²) in patients with mBC or GBM, and to evaluate effects of concomitant use of enzyme-inducing anticonvulsants (EIAC) on edotecarin PK in GBM patients. Methods: Edotecarin was administered via 1-hr IV infusion every 3 weeks at a dose of 11 to 15 mg/m² in mBC patients and 13 mg/m² in GBM patients. Serial plasma samples for PK evaluation were collected for up to 96 hrs after edotecarin treatment in 26 mBC patients and 30 GBM patients (13 receiving concurrent EIAC therapy and 17 receiving no EIAC therapy). Plasma concentration-time data from each patient population were analyzed by noncompartmental Methods: Results: Steady-state plasma concentrations were rapidly achieved during the infusion. After stop of the infusion, the concentrations followed a bi-exponential decline with a very steep initial phase and a relatively shallow terminal phase. No apparent difference in PK parameters was observed between mBC and GBM patients. The AUC_0- and Cmax were comparable between cycle 1 and cycle 2 in BC patients, indicating little or no accumulation in plasma exposure when edotecarin was dosed every 3 weeks. AUC_0- and Cmax were similar between GBM patients treated with or without EIAC therapy. Edotecarin has a plasma clearance (CL) of 45 to 53 L/hr/m², a volume of distribution (Vss) of 650 to 850 L/m², and a terminal half-life of approximately 20 to 25 hours. Conclusions: Edotecarin has a moderate plasma CL and a large volume of distribution in cancer patients. The PK is not different in mBC and GBM patients. Consistent with previous data suggesting biliary excretion as the major route of edotecarin elimination, concurrent EIAC therapy in GBM patients has no apparent effect on edotecarin PK.

Author Disclosure

Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer

Abstract presentation from the 2005 ASCO Annual Meeting