Flavopiridol, a Novel Cyclin-Dependent Kinase Inhibitor, in Clinical Development

2002 ◽  
Vol 36 (5) ◽  
pp. 905-911 ◽  
Author(s):  
Suoping Zhai ◽  
Adrian M Senderowicz ◽  
Edward A Sausville ◽  
William D Figg
Keyword(s):  
Clinical Trials ◽  
Antitumor Activity ◽  
Phase I ◽  
Kinase Inhibitor ◽  
Data Extraction ◽  
Single Agent ◽  
Clinical Information ◽  
Antitumor Agent ◽  
Medline Search ◽  
Phase I And Ii

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 (≤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?

scholarly journals Activity of 129 Single-Agent Drugs in 228 Phase I and II Clinical Trials in Multiple Myeloma

2014 ◽  
Vol 14 (4) ◽  
pp. 284-290.e5 ◽  
Author(s):  
K. Martin Kortuem ◽  
Kaitlyn Zidich ◽  
Steven R. Schuster ◽  
Meaghan L. Khan ◽  
Victor H. Jimenez-Zepeda ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Phase I ◽  
Single Agent ◽  
Phase I And Ii

scholarly journals Osteosarcoma Pathogenesis Leads the Way to New Target Treatments

2021 ◽  
Vol 22 (2) ◽  
pp. 813
Author(s):  
Isabel Fernandes ◽  
Cecília Melo-Alvim ◽  
Raquel Lopes-Brás ◽  
Miguel Esperança-Martins ◽  
Luís Costa
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Poor Prognosis ◽  
Therapeutic Targets ◽  
Rare Condition ◽  
Basic Research ◽  
Metastatic Setting ◽  
Phase I And Ii ◽  
The Way

Osteosarcoma (OS) is a rare condition with very poor prognosis in a metastatic setting. Basic research has enabled a better understanding of OS pathogenesis and the discovery of new potential therapeutic targets. Phase I and II clinical trials are already ongoing, with some promising results for these patients. This article reviews OS pathogenesis and new potential therapeutic targets.

Toxicity profiles of HER2/neupeptide anticancer vaccines: the picture from Phase/I and II clinical trials

2012 ◽  
Vol 11 (6) ◽  
pp. 637-640 ◽  
Author(s):  
Constantin N Baxevanis ◽  
Michael Papamichail ◽  
Sonia A Perez
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Anticancer Vaccines ◽  
Phase I And Ii

Leukotriene-Receptor Antagonists and 5-Lipoxygenase Inhibitors in Asthma

1993 ◽  
Vol 27 (7-8) ◽  
pp. 898-903 ◽  
Author(s):  
Julie S. Larsen ◽  
Edward P. Acosta
Keyword(s):  
Clinical Trials ◽  
English Language ◽  
Data Extraction ◽  
Background Information ◽  
Receptor Antagonists ◽  
Lipoxygenase Inhibitors ◽  
Medline Search ◽  
Leukotriene Receptor Antagonists ◽  
Patient Tolerance ◽  
Leukotriene Receptor

OBJECTIVE: To familiarize readers with a potentially new class of compounds for treating asthma. Background information on leukotrienes is provided in addition to an indepth review of pertinent clinical trials. DATA SOURCES: Information was obtained from controlled clinical trials, abstracts, and review articles identified through a MEDLINE search of English-language articles. STUDY SELECTION: Emphasis was placed on early clinical trials that showed some benefit with these compounds as well as more recent studies using newer agents that produced more promising results. DATA EXTRACTION: Information regarding leukotriene biochemistry was extracted from basic science research and data from human studies were evaluated by the authors according to patient selection, study design, methodology, and therapeutic response. DATA SYNTHESIS: Leukotrienes have a pathophysiologic role in asthma. Two distinct but pharmacologically similar classes of leukotriene inhibitors are currently being clinically evaluated. These are leukotriene receptor antagonists and 5-lipoxygenase inhibitors. Early clinical trials with these agents yielded unfavorable results primarily because of lack of drug potency and selectivity, poor patient tolerance, and possibly the route of administration. Subsequent studies with more potent and selective agents have further implicated leukotrienes as biochemical mediators in asthma and, consequently, have shown promising clinical outcomes with respect to pulmonary function testing and patient tolerance. CONCLUSIONS: Advancements in the pathogenesis of asthma are beginning to define a role for the leukotrienes. Although more studies are needed to assess the efficacy of leukotriene inhibitors, recent clinical trials using leukotriene-receptor antagonists and 5-lipoxygenase inhibitors indicate a potential for the expansion of therapeutic regimens currently used in the treatment of asthma.

scholarly journals Automated data extraction software for medical summary using text mining (T-Library)

2019 ◽  
Author(s):  
Tomohide Yamada ◽  
Yoshinobu Kondo ◽  
Ryo Momosaki
Keyword(s):  
Clinical Trials ◽  
Deep Learning ◽  
Clinical Research ◽  
Data Extraction ◽  
Healthcare Providers ◽  
Clinical Information ◽  
Patient Records ◽  
Unstructured Text ◽  
Risk Engine ◽  
Easy Operation

The electronic medical record (EMR) is a source of clinical information and is used for clinical research. Clinical researchers leverage this information by employing staffs to manually extracting data from the unstructured text. This process can be both error-prone and labor-intensive. This software (T-Library) is a software which automatically extracts key clinical data from patient records and can potentially help healthcare providers and researchers save money, make treatment decisions and manage clinical trials. This software saves labor for data transcription in clinical research. This is a vital step toward getting researchers rapid access to the information they need. This is also the attempt to cluster patients’ morbid states and establish accurate and constantly updated risk engine of complications’ crises, using deep learning. Strengths: 1) Quick and Easy operation URL: http://www.picoron.com/tlibrary/

Investigational treatments in phase I and II clinical trials: a systematic review in chronic obstructive pulmonary disease (COPD)

2020 ◽  
Vol 29 (7) ◽  
pp. 723-738
Author(s):  
Luigino Calzetta ◽  
Beatrice Ludovica Ritondo ◽  
Maria Gabriella Matera ◽  
Gabriella Pezzuto ◽  
Mario Cazzola ◽  
...  
Keyword(s):  
Systematic Review ◽  
Chronic Obstructive Pulmonary Disease ◽  
Clinical Trials ◽  
Phase I ◽  
Pulmonary Disease ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Phase I And Ii

Efficacy of STI571, an Abl tyrosine kinase inhibitor, in conjunction with other antileukemic agents against Bcr-Abl–positive cells

Blood ◽  
2000 ◽  
Vol 96 (9) ◽  
pp. 3195-3199 ◽  
Author(s):  
J. Tyler Thiesing ◽  
Sayuri Ohno-Jones ◽  
Kathryn S. Kolibaba ◽  
Brian J. Druker
Keyword(s):  
Clinical Trials ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Kinase Inhibitor ◽  
Single Agent ◽  
Myelogenous Leukemia ◽  
Hematopoietic Stem ◽  
Abl Tyrosine Kinase ◽  
Abl Tyrosine Kinase Inhibitor

Abstract Chronic myelogenous leukemia (CML), a malignancy of a hematopoietic stem cell, is caused by the Bcr-Abl tyrosine kinase. STI571(formerly CGP 57148B), an Abl tyrosine kinase inhibitor, has specific in vitro antileukemic activity against Bcr-Abl–positive cells and is currently in Phase II clinical trials. As it is likely that resistance to a single agent would be observed, combinations of STI571 with other antileukemic agents have been evaluated for activity against Bcr-Abl–positive cell lines and in colony-forming assays in vitro. The specific antileukemic agents tested included several agents currently used for the treatment of CML: interferon-alpha (IFN), hydroxyurea (HU), daunorubicin (DNR), and cytosine arabinoside (Ara-C). In proliferation assays that use Bcr-Abl–expressing cells lines, the combination of STI571 with IFN, DNR, and Ara-C showed additive or synergistic effects, whereas the combination of STI571 and HU demonstrated antagonistic effects. However, in colony-forming assays that use CML patient samples, all combinations showed increased antiproliferative effects as compared with STI571 alone. These data indicate that combinations of STI571 with IFN, DNR, or Ara-C may be more useful than STI571 alone in the treatment of CML and suggest consideration of clinical trials of these combinations.

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