Treatment of anthracycline extravasation with dexrazoxane

Accidental extravasation of anthracyclines is a feared complication. Presen t treatment consists of local cooling and extensive surgical debridement, w hich often results in severe morbidity, All clinically important anthracycl ines are topoisomerase II poisons that are antagonized by topoisomerase II catalytic inhibitors such as dexrazoxane, Therefore, we investigated whethe r dexrazoxane protects against extravasation lesions caused by anthracyclin es. B6D2F1 mice received s.c. daunorubicin, doxorubicin, or idarubicin foll owed by systemic treatment with dexrazoxane or saline. One single systemic dose of dexrazoxane immediately after s.c. administration of doxorubicin, d aunorubicin, or idarubicin reduced the tissue lesions (expressed as area un der the curve of wound size times duration) by 96% (P < 0.0001), 70% (P < 0 .0001), and 87% (P = 0.0004), respectively. Moreover, the treatment resulte d in a statistically significant reduction in the fraction of mice with wou nds as well as the duration of wounds, The induction of wounds was dose-dep endent, as was the degree of protection by dexrazoxane, Dexrazoxane could b e administered up to 3 h after the anthracycline without loss of protection , Triple-dosage of dexrazoxane tended to be more effective than a single in jection. Dexrazoxane had no effect on lesions induced by hydrogen peroxide, This is the first report of use of a topoisomerase IZ catalytic inhibitor such as dexrazoxane in the treatment of anthracycline extravasation injurie s. These convincing preclinical data represent a novel nontoxic approach th at can easily be implemented into the clinical handling of accidental extra vasation of anthracyclines.