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

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

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Summary: 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.

Original languageEnglish
Pages (from-to)650-658
Number of pages9
JournalInvestigational New Drugs
Volume28
Issue number5
DOIs
Publication statusPublished - 2010 Oct

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

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