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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

Identifieur interne : 004729 ( Ncbi/Curation ); précédent : 004728; suivant : 004730

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

Auteurs : Stephanie M. Cohen [États-Unis] ; Ridhwi Mukerji [États-Unis] ; Shuang Cai [États-Unis] ; Ivan Damjanov [États-Unis] ; M. Laird Forrest [États-Unis] ; Mark S. Cohen [États-Unis]

Source :

American journal of surgery [ 0002-9610 ] ; 2011.

RBID : PMC:5198781

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.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5198781

DOI: 10.1016/j.amjsurg.2011.06.027
PubMed: 21982998
PubMed Central: 5198781

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PMC:5198781

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</sec>
<sec id="S2"><title>Methods</title>
<p id="P2">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.</p>
</sec>
<sec id="S3"><title>Results</title>
<p id="P3">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).</p>
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<sec id="S4"><title>Conclusion</title>
<p id="P4">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.</p>
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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

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

Source :

Abstract

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