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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.

Authors
 Sang Joon Shin ; Joong Bae Ahn ; Hyun Cheol Chung ; Chin Kim ; Dal-Hyun Kim ; Jae Kyung Roh ; Sun Young Rha ; Hye Ryun Kim ; Tae Won Kim ; Yong Sang Hong ; Yoon Jung Lee ; Kyung Soo Park 
Citation
 Investigational New Drugs, Vol.30(2) : 672~680, 2012 
Journal Title
 Investigational New Drugs 
ISSN
 0167-6997 
Issue Date
2012
Abstract
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.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/90568
DOI
10.1007/s10637-010-9625-x
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Internal Medicine
1. 연구논문 > 1. College of Medicine > Dept. of Pharmacology
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Link
 http://link.springer.com/article/10.1007%2Fs10637-010-9625-x
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