Document Detail

Preclinical pharmacology of the taxanes: implications of the differences.
MedLine Citation:
PMID:  15161985     Owner:  NLM     Status:  MEDLINE    
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.
Joseph Gligorov; Jean Pierre Lotz
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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    
CancerEst, APHP Tenon, Medical Oncology, Paris, France.
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MeSH Terms
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
Maximum Tolerated Dose
Neoplasms / drug therapy*,  mortality,  pathology
Paclitaxel / administration & dosage,  adverse effects,  pharmacokinetics
Survival Rate
Taxoids / administration & dosage*,  adverse effects,  pharmacokinetics*
Reg. No./Substance:
0/Taxoids; 15H5577CQD/docetaxel; 33069-62-4/Paclitaxel

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

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