کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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4279867 | 1611536 | 2011 | 8 صفحه PDF | دانلود رایگان |
BackgroundCombination 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.MethodsFemale 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.ResultsEfficacy 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).ConclusionsSubcutaneous 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.
Journal: The American Journal of Surgery - Volume 202, Issue 6, December 2011, Pages 646–653