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.

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
Abstract/OtherAbstract:	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.

Authors:	Stephanie M Cohen; Ridhwi Mukerji; Shuang Cai; Ivan Damjanov; M Laird Forrest; Mark S Cohen
Related Documents :	18841478 - Peritoneal mesothelioma. 21732338 - Fludarabine plus cyclophosphamide and rituximab in waldenstrom macroglobulinemia: an ef... 10763038 - Current therapy for mesothelioma. 3433368 - The treatment of metastatic pleural effusion in breast cancer: report of 25 cases. 21092288 - Hypofractionated radiotherapy after conservative surgery for breast cancer: analysis of... 2980978 - Solitary spinal plasmacytomas: management and outcome.
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.
Affiliation:	Department of Surgery, University of Kansas Medical Center, Kansas City, KS, USA.
Export Citation:	APA/MLA Format Download EndNote Download BibTex
MeSH Terms
Descriptor/Qualifier:

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

Previous Document: Clinical outcomes of manual bowel decompression (milking) in the mechanical small bowel obstruction:...
Next Document: Resident fatigue in 2010: Where is the beef?