© 2001 Kluwer Academic Publishers. Printed in the Netherlands. Original article Dexrazoxane is a potent and specific inhibitor of anthracycline induced subcutaneous lesions in micej

' Background ^ Recently, we have shown that dexrazoxane (ICRF-187) is an effective antidote against accidental extrava-sation of anthracyclines. Thus, it inhibits the lesions induced by subcutaneous (s.c.) daunorubicin, idarubicin, and doxo-rubicin in mice and has proven to be successful clinically as well. Dexrazoxane is a potent metal ion chelator as well as being a catalytic inhibitor of DNA topoisomerase II. However, the mechanism behind the protection against anthracycline extravasation is not known. Mgierialsjiml methods: Mice were injected s.c. with dauno-rubicin or doxorubicin. Systemic N-acetylcysteine, alfa-toco-ferol, amifostine, merbarone, aclarubicin, 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 healing of all wounds. Results: Triple-treatment with systemic dexrazoxane was superior to single dosage and completely prevented lesions after s.c. daunorubicin and doxorubicin. Low-dose i.l. dexra-zoxane was effective in protecting as well. In contrast, none of the other seven adjuvants was effective. Protection was not achieved with local cooling, however, topical ice did not impair the efficacy of dexrazoxane. Conclusions; Dexrazoxane is extremely effective and appa-rerffly quite specific in protecting against lesions after s.c. doxorubicin and daunorubicin.