Document Detail


Preclinical pharmacology of the taxanes: implications of the differences.
MedLine Citation:
PMID:  15161985     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Taxanes are one of the most powerful classes of compounds among all chemotherapeutic drugs. Only 30 years separate the isolation of the first taxane from the results of direct clinical comparisons in metastatic breast, ovarian, and lung cancer between the two taxanes available in routine clinical practice. These results suggest a more favorable benefit-to-risk ratio for docetaxel compared to paclitaxel when these drugs are used as single agents or in combination with other chemotherapeutic agents in an every-3-week dosing regimen. Pharmacological data support the difference between the taxanes, likely explaining the clinical results. Considering the molecular pharmacology of the two drugs, docetaxel appears to bind to beta-tubulin with greater affinity and has a wider cell cycle activity than paclitaxel. Docetaxel also appears to have direct antitumoral activity via an apoptotic effect mediated by bcl-2 phosphorylation. In addition, docetaxel has a longer retention time in tumor cells than paclitaxel because of greater uptake and slower efflux. Pharmacokinetics and pharmacodynamics of the taxanes show both agents to be extensively metabolized in the liver, and paclitaxel has a nonlinear pharmacokinetic behavior while docetaxel has linear pharmacokinetics. These differences explain the more simple treatment schedule and favorable results for docetaxel as a single agent and in combination therapy. Last, but not least, there is a pharmacokinetic interaction between paclitaxel and the anthracyclines, an active class of compounds commonly used in the treatment of breast cancer. This pharmacokinetic interaction is associated with greater cardio- and myelotoxicities, which are sequence dependent. These pharmacological data likely explain the different clinical development strategies for the two molecules as well as the different clinical results from individual trials and direct comparisons.
Authors:
Joseph Gligorov; Jean Pierre Lotz
Related Documents :
19901115 - Clinical activity of gemcitabine plus pertuzumab in platinum-resistant ovarian cancer, ...
4017165 - A phase ii study of sequential methotrexate and fluorouracil in advanced colorectal can...
25342505 - Lack of association between xpf polymorphisms and gastric cancer risk: a meta-analysis.
8452115 - A phase ii study of 5-fluorouracil, cisplatin, and 4'-epirubicin in the treatment of ad...
10736615 - Energy sources and risk of cancer of the breast and colon-rectum in italy.
23963195 - Adolescents' and young adults' experiences of childhood cancer: descriptions of daily l...
Publication Detail:
Type:  Comparative Study; Journal Article; Review    
Journal Detail:
Title:  The oncologist     Volume:  9 Suppl 2     ISSN:  1083-7159     ISO Abbreviation:  Oncologist     Publication Date:  2004  
Date Detail:
Created Date:  2004-05-26     Completed Date:  2004-08-25     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  9607837     Medline TA:  Oncologist     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3-8     Citation Subset:  IM    
Affiliation:
CancerEst, APHP Tenon, Medical Oncology, Paris, France. joseph.gligorov@tnn.ap-hop-paris.fr
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Antineoplastic Combined Chemotherapy Protocols / administration & dosage
Biological Availability
Clinical Trials, Phase I as Topic
Clinical Trials, Phase II as Topic
Clinical Trials, Phase III as Topic
Dose-Response Relationship, Drug
Drug Administration Schedule
Drug Interactions
Humans
Maximum Tolerated Dose
Neoplasms / drug therapy*,  mortality,  pathology
Paclitaxel / administration & dosage,  adverse effects,  pharmacokinetics
Prognosis
Survival Rate
Taxoids / administration & dosage*,  adverse effects,  pharmacokinetics*
Chemical
Reg. No./Substance:
0/Taxoids; 15H5577CQD/docetaxel; 33069-62-4/Paclitaxel

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


Previous Document:  Analysis of the relationship between disease activity and damage in patients with systemic lupus ery...
Next Document:  The treatment of advanced gastric cancer: new findings on the activity of the taxanes.