Document Detail


Flavopiridol, a novel cyclin-dependent kinase inhibitor, in clinical development.
MedLine Citation:
PMID:  11978170     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To review preclinical and clinical information on flavopiridol, an inhibitor of cyclin-dependent kinases (CDKs), tested as an antitumor agent. DATA SOURCES: Primary and review articles were identified by MEDLINE search (1990-June 2001). Abstracts from recent meetings were also used as source materials. DATA EXTRACTION: Flavopiridol was reviewed with regard to its mechanisms, preclinical and clinical results, pharmacokinetics, and metabolism. DATA SYNTHESIS: Flavopiridol is an inhibitor of several CDKs and displays unique anticancer properties. In addition to direct CDK inhibition, flavopiridol also exhibited other features such as inducing apoptosis in many cancer cell lines, decreasing cyclin D1 concentration, and inhibiting angiogenesis. Preclinical xenograft models showed significant antitumor activity for flavopiridol. The regimen using 72-hour continuous infusion every 2 weeks has been most extensively applied in clinical trials, with a 1-hour infusion currently being explored to achieve higher peak concentrations. Several Phase I and II trials have been reported, with some evidence of antitumor activity noted. Further Phase I and II trials using flavopiridol as a single agent and in combination with standard chemotherapeutic regimens and various tumor types are ongoing. CONCLUSIONS: Flavopiridol is the first CDK inhibitor to enter clinical trials. Several Phase I and Phase II clinical trials with different regimens (72-h or 1-h infusion) have been completed. Initial clinical trials have been intriguing, but many questions remain: What is the best regimen (< or =72-h infusion)? Does optimal future development of this drug depend on the combination with other chemotherapy? What is the best combination of flavopiridol with other chemotherapy?
Authors:
Suoping Zhai; Adrian M Senderowicz; Edward A Sausville; William D Figg
Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  The Annals of pharmacotherapy     Volume:  36     ISSN:  1060-0280     ISO Abbreviation:  Ann Pharmacother     Publication Date:  2002 May 
Date Detail:
Created Date:  2002-04-29     Completed Date:  2002-10-18     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9203131     Medline TA:  Ann Pharmacother     Country:  United States    
Other Details:
Languages:  eng     Pagination:  905-11     Citation Subset:  IM    
Affiliation:
Center for Cancer Research, National Cancer Institute, Building 10 Room 5A01, 9000 Rockville Pike, Bethesda, MD 20892, USA.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / adverse effects,  pharmacokinetics,  therapeutic use*
Clinical Trials, Phase I as Topic
Clinical Trials, Phase II as Topic
Colonic Neoplasms / drug therapy
Cyclin-Dependent Kinases / antagonists & inhibitors*
Diarrhea / chemically induced
Drug Evaluation, Preclinical
Drug Therapy, Combination
Fatigue / chemically induced
Flavonoids / adverse effects,  pharmacokinetics,  therapeutic use*
Humans
Infusion Pumps
Kidney Neoplasms / drug therapy
Lymphoma, Non-Hodgkin / drug therapy
Neoplasms / drug therapy*
Neutropenia / chemically induced
Piperidines / adverse effects,  pharmacokinetics,  therapeutic use*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Flavonoids; 0/Piperidines; 146426-40-6/flavopiridol; EC 2.7.11.22/Cyclin-Dependent Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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