A phase I pharmacokinetic and pharmacodynamic study of CKD-732, an antiangiogenic agent, in patients with refractory solid cancer View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2009-07-08

AUTHORS

Sang Joon Shin, Hei-Cheul Jeung, Joong Bae Ahn, Sun Young Rha, Jae Kyung Roh, Kyung Soo Park, Dal-Hyun Kim, Chin Kim, Hyun Cheol Chung

ABSTRACT

We conducted a phase I trial of the antiangiogenic agent 6-O-(4-dimethylaminoethoxy) cinnamoyl fumagillol hemioxalate (CKD-732). Our aims were to determine the maximum tolerated dose (MTD), pharmacokinetics (PK), and safety profiles as well as identify the biologically active dose (BAD) from ex vivo pharmacodynamics (PD) and biomarkers of CKD-732. Using a dose escalation schedule, 19 patients with refractory solid tumors were enrolled at dose levels of CKD-732 ranging from 1 to 15 mg/m2 given twice weekly for 2 weeks followed by a 1-week rest. No treatment-related deaths occurred in this study. Confusion and insomnia were dose-limiting toxicities (DLTs), and MTD was 15 mg/m2. The area under the concentration-time curve (AUC) and maximum concentration (Cmax) increased dose dependently with increasing doses. The BAD was 5 mg/m2 according to ex vivo PD. A decrement in soluble vascular endothelial growth factor receptor-3 (sVEGF-3) level was correlated with a reduction in tumor size (r = 0.54, P = 0.045). The results from this study showed an MTD of 15 mg/m2 and a BAD of 5 mg/m2. More... »

PAGES

650-658

Journal

TITLE

Investigational New Drugs

ISSUE

5

VOLUME

28

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s10637-009-9287-8

    DOI

    http://dx.doi.org/10.1007/s10637-009-9287-8

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1026992841

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/19585083


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    32 schema:description We conducted a phase I trial of the antiangiogenic agent 6-O-(4-dimethylaminoethoxy) cinnamoyl fumagillol hemioxalate (CKD-732). Our aims were to determine the maximum tolerated dose (MTD), pharmacokinetics (PK), and safety profiles as well as identify the biologically active dose (BAD) from ex vivo pharmacodynamics (PD) and biomarkers of CKD-732. Using a dose escalation schedule, 19 patients with refractory solid tumors were enrolled at dose levels of CKD-732 ranging from 1 to 15 mg/m2 given twice weekly for 2 weeks followed by a 1-week rest. No treatment-related deaths occurred in this study. Confusion and insomnia were dose-limiting toxicities (DLTs), and MTD was 15 mg/m2. The area under the concentration-time curve (AUC) and maximum concentration (Cmax) increased dose dependently with increasing doses. The BAD was 5 mg/m2 according to ex vivo PD. A decrement in soluble vascular endothelial growth factor receptor-3 (sVEGF-3) level was correlated with a reduction in tumor size (r = 0.54, P = 0.045). The results from this study showed an MTD of 15 mg/m2 and a BAD of 5 mg/m2.
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