Document Detail


Bevacizumab improves the delivery and efficacy of paclitaxel.
MedLine Citation:
PMID:  20559127     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
It has been reported that bevacizumab in combination with paclitaxel significantly prolongs progression-free survival compared with paclitaxel alone in the initial treatment for metastatic breast cancer. To understand how bevacizumab enhances the efficacy of paclitaxel, we investigated the mechanism in a MX-1 human breast cancer xenograft model. The antitumor activity of bevacizumab at 5 mg/kg in combination with paclitaxel at 20 or 30 mg/kg was significantly higher than that of either agent alone. First, we measured the paclitaxel concentration in tumor to see whether bevacizumab enhances the activity by increasing the tumor concentration of paclitaxel. When given in combination with bevacizumab, the levels of paclitaxel in the tumor increased. Paclitaxel at 30 mg/kg with bevacizumab showed a similar tumor concentration as paclitaxel alone at either 60 or 100 mg/kg, with a similar degree of tumor growth inhibition. In contrast, no remarkable differences in paclitaxel concentration in the plasma or liver were observed between the paclitaxel monotherapy group and the paclitaxel plus bevacizumab group. An increase in paclitaxel concentration by bevacizumab was also found in another model, A549. In the same MX-1 model, vascular permeability in the tumor was significantly decreased by treatment with bevacizumab. There was no difference in microvessel density between the bevacizumab alone group and the combination group. Results suggest that the synergistic antitumor activity of paclitaxel and bevacizumab in combination may be a result of the increase in paclitaxel concentration in tumor resulting from the downregulation of vascular permeability when co-administered with bevacizumab.
Authors:
Mieko Yanagisawa; Keigo Yorozu; Mitsue Kurasawa; Kohnosuke Nakano; Koh Furugaki; Yoriko Yamashita; Kazushige Mori; Kaori Fujimoto-Ouchi
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Anti-cancer drugs     Volume:  21     ISSN:  1473-5741     ISO Abbreviation:  Anticancer Drugs     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-08     Completed Date:  2010-08-04     Revised Date:  2013-05-27    
Medline Journal Info:
Nlm Unique ID:  9100823     Medline TA:  Anticancer Drugs     Country:  England    
Other Details:
Languages:  eng     Pagination:  687-94     Citation Subset:  IM    
Affiliation:
Department of Product Research, Chugai Pharmaceutical Co., Ltd., Kajiwara, Kamakura, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / administration & dosage,  therapeutic use*
Antibodies, Monoclonal, Humanized
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Breast Neoplasms / drug therapy*
Cell Membrane Permeability / drug effects
Drug Synergism
Female
Humans
Male
Mice
Paclitaxel / administration & dosage,  pharmacokinetics,  therapeutic use*
Tissue Distribution / drug effects
Treatment Outcome
Xenograft Model Antitumor Assays
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antibodies, Monoclonal, Humanized; 2S9ZZM9Q9V/bevacizumab; 33069-62-4/Paclitaxel

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


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