Dexrazoxane is a potent and specific inhibitor of anthracycline induced subcutaneous lesions in mice

Background: Recently, we have shown that dexrazoxane (ICRF-187) is an effec tive antidote against accidental extravasation of anthracyclines. Thus, it inhibits the lesions induced by subcutaneous (s.c.) daunorubicin, idarubici n, and doxorubicin in mice and has proven to be successful clinically as we ll. Dexrazoxane is a potent metal ion chelator as well as being a catalytic inhibitor of DNA topoisomerase II. However, the mechanism behind the prote ction against anthracycline extravasation is not known. Materials and methods: Mice were injected s.c. with daunorubicin or doxorub icin. Systemic N-acetylcysteine, alfa-tocoferol, amifostine, merbarone, acl arubicin, ADR-925, and EDTA were administered i.p. immediately hereafter or as a triple-treatment over six hours. Intralesional (i.l.) adjuvants were injected immediately after and into the same area as the anthracycline. The frequency, duration, and sizes of wounds were observed until complete heal ing of all wounds. Results: Triple-treatment with systemic dexrazoxane was superior to single dosage and completely prevented lesions after s.c. daunorubicin and doxorub icin. Low-dose i.l. dexrazoxane was effective in protecting as well. In con trast, none of the other seven adjuvants was effective. Protection was not achieved with local cooling, however, topical ice did not impair the effica cy of dexrazoxane. Conclusions: Dexrazoxane is extremely effective and apparently quite specif ic in protecting against lesions after s.c. doxorubicin and daunorubicin.