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Subcutaneous delivery of nanoconjugated doxorubicin and cisplatin for locally advanced breast cancer demonstrates improved efficacy and decreased toxicity at lower doses than standard systemic combination therapy in vivo.
MedLine Citation:
PMID:  21982998     Owner:  NLM     Status:  Publisher    
BACKGROUND: Combination cytotoxic agents in breast cancer carry dose-limiting toxicities. The aim of this study was to test the hypothesis that nanocarrier-conjugated doxorubicin and cisplatin would have improved tumor efficacy with decreased systemic toxicity over standard drugs, even at lower doses. METHODS: Female Nu/Nu mice were injected in the breast with human MDA-MB-468LN cells and treated with either standard or nanocarrier-conjugated combination therapy (doxorubicin plus cisplatin) at 50% or 75% maximum tolerated dose (MTD) and monitored for efficacy and toxicity over 12 weeks. RESULTS: Efficacy results for mice treated with hyaluronan-conjugated doxorubicin and cisplatin at 50% MTD were as follows: 5 complete responses, 2 partial responses, and 1 case of stable disease. For hyaluronan-conjugated doxorubicin and cisplatin at 75% MTD, efficacy results were as follows: 7 complete responses, 1 partial response. All complete responses were confirmed histologically. In comparison, mice given standard doxorubicin and cisplatin at 50% MTD demonstrated progressive disease in 6, stable disease in 1, and partial response in 1. For standard doxorubicin and cisplatin at 75% MTD, there were 5 cases of progressive disease and 3 of stable disease (P < .0001 on multivariate analysis of variance). At 75% MTD, standard drug-treated mice had significant weight loss compared to nanocarrier drug-treated mice (P < .001). CONCLUSIONS: Subcutaneous nanocarrier delivery of doxorubicin and cisplatin demonstrated significantly improved efficacy with decreased toxicity compared with standard agent combination therapy at all doses tested, achieving complete pathologic tumor response.
Stephanie M Cohen; Ridhwi Mukerji; Shuang Cai; Ivan Damjanov; M Laird Forrest; Mark S Cohen
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-10-7
Journal Detail:
Title:  American journal of surgery     Volume:  -     ISSN:  1879-1883     ISO Abbreviation:  -     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370473     Medline TA:  Am J Surg     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Department of Surgery, University of Kansas Medical Center, Kansas City, KS, USA.
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