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

View/ Open
Issue Date
2011-10-08Author
Cohen, Stephanie M.
Mukerji, Ridhwi
Cai, Shuang
Damjanov, Ivan
Forrest, M. Laird
Cohen, Mark S.
Publisher
Elsevier
Type
Article
Article Version
Scholarly/refereed, author accepted manuscript
Rights
Copyright © 2011 Elsevier Inc. All rights reserved.
Metadata
Show full item recordAbstract
Background—Combination cytotoxic agents in breast cancer carry dose-limiting toxicities. We
hypothesize that nanocarrier-conjugated doxorubicin and cisplatin will 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
+cisplatin) at 50% or 75% MTD, and monitored for efficacy and toxicity over 12-weeks.Results—Efficacy results for mice treated with HA-conjugated doxorubicin/cisplatin at 50%
MTD include:[complete responses(CR)=5, partial responses(PR)=2, and stable disease(SD)=1]and
for HA-conjugated dox/cis at 75% MTD:[CR=7,PR=1; all CR’s confirmed histologically]. In
comparison, mice given standard dox/cis(50% MTD)demonstrated:[progressive disease(PD)=6,
SD=1, and PR=1] and for standard dox/cis(75% MTD):[PD=5,SD=3; p<0.0001 on multivariate
ANOVA]. At 75% MTD, standard drug-treated mice had significant weight loss compared to
nanocarrier drug-treated mice(p<0.001).Conclusion—Subcutaneous nanocarrier-delivery of doxorubicin and cisplatin demonstrated
significantly improved efficacy with decreased toxicity compared to standard agent combination
therapy at all doses tested achieving complete pathologic tumor response.
Collections
Citation
Cohen, S. M., Mukerji, R., Cai, S., Damjanov, I., Forrest, M. L., & Cohen, M. S. (2011). 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. American Journal of Surgery, 202(6), 646–653. http://doi.org/10.1016/j.amjsurg.2011.06.027
Items in KU ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
We want to hear from you! Please share your stories about how Open Access to this item benefits YOU.