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A Phase Ib pharmacokinetic study of the anti-angiogenic agent CKD-732 used in combination with capecitabine and oxaliplatin (XELOX) in metastatic colorectal cancer patients who progressed on irinotecan-based chemotherapy.

 Sang Joon Shin  ;  Joong Bae Ahn  ;  Kyung Soo Park  ;  Yoon Jung Lee  ;  Yong Sang Hong  ;  Tae Won Kim  ;  Hye Ryun Kim  ;  Sun Young Rha  ;  Jae Kyung Roh  ;  Dal-Hyun Kim  ;  Chin Kim  ;  Hyun Cheol Chung 
 Investigational New Drugs, Vol.30(2) : 672-680, 2012 
Journal Title
 Investigational New Drugs 
Issue Date
BACKGROUND: We conducted a Phase I clinical trial to evaluate the safety, tolerability, and pharmacokinetics (PK) of CKD-732 [6-O-(4-dimethylaminoethoxy) cinnamoyl fumagillol hemioxalate] in combination with capecitabine and oxaliplatin (XELOX) in nine metastatic colorectal cancer patients who had progressed on irinotecan-based chemotherapy. METHODS: Using a dose-escalation schedule, CKD-732 doses of 2, 5, or 10 mg/m(2)/d were administered twice weekly for 2 weeks, followed by a 1-week rest. Oxaliplatin (130 mg/m(2)) was administered on day 1, and capecitabine (1,000 mg/m(2) twice a day) was orally administered for 14 days of a 3-week cycle. RESULTS: In the group given the 10 mg/m(2)/d dose, two patients experienced dose limiting toxicities (one had grade 3 nausea, insomnia, and fatigue; the other had grade 3 insomnia). The maximum tolerated dose was 10 mg/m(2)/d, and the clinically recommended dose was 5 mg/m(2)/d for CKD-732 in combination with XELOX. Frequently encountered non-hematological grade 3/4 adverse events included insomnia (22.2%), fatigue (11.1%), sensory neuropathy (11.1%), hyperbilirubinemia (11.1%), and dyspnea (11.1%). The area under the concentration-time curve and maximum concentration of CKD-732 increased in a dose-dependent manner. There were no notable effects of CKD-732 on the PK of capecitabine and oxaliplatin-derived platinum. CONCLUSION: The Phase II recommended dose of CKD-732 was determined to be 5 mg/m(2)/d, and this dose was safely combined with a conventional dose of capecitabine and oxaliplatin in this patient population. Further studies on the effects of CKD-732 in combination with XELOX and other chemotherapies using a larger study population are warranted.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
김혜련(Kim, Hye Ryun) ORCID logo https://orcid.org/0000-0002-1842-9070
노재경(Roh, Jae Kyung)
라선영(Rha, Sun Young) ORCID logo https://orcid.org/0000-0002-2512-4531
박경수(Park, Kyungsoo) ORCID logo https://orcid.org/0000-0002-6972-1143
신상준(Shin, Sang Joon) ORCID logo https://orcid.org/0000-0001-5350-7241
안중배(Ahn, Joong Bae) ORCID logo https://orcid.org/0000-0001-6787-1503
이윤정(Lee, Yoon Jung)
정현철(Chung, Hyun Cheol) ORCID logo https://orcid.org/0000-0002-0920-9471
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