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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
Cohen, Stephanie M. Mukerji, Ridhwi Cai, Shuang Damjanov, Ivan Forrest, M. Laird Cohen, Mark S.
Cohen, Stephanie M.
Mukerji, Ridhwi
Cai, Shuang
Damjanov, Ivan
Forrest, M. Laird
Cohen, Mark S.
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Abstract
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.
Description
Date
2011-10-08
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Publisher
Elsevier
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Keywords
Nanocarriers, Drug-delivery, Combination chemotherapy, Hyaluronic acid, Breast cancer, Locoregional therapy
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