| 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. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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
Previous Document: Development of a pharmacist-managed lipid clinic.
Next Document: Combination drug therapy for gastroesophageal reflux disease.