Journal
ANNALS OF ONCOLOGY
Volume 12, Issue 3, Pages 405-410Publisher
KLUWER ACADEMIC PUBL
DOI: 10.1023/A:1011163823321
Keywords
anthracycline; catalytic inhibitor; dexrazoxane (ICRF-187); extravasation; free radical scavenger; topoisomerase II
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Background: Recently, we have shown that dexrazoxane (ICRF-187) is an effective antidote against accidental extravasation of anthracyclines. Thus, it inhibits the lesions induced by subcutaneous (s.c.) daunorubicin, idarubicin, and doxorubicin 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. Materials and methods: Mice were injected s.c. with daunorubicin or doxorubicin. Systemic N-acetylcysteine, alfa-tocoferol, 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. dexrazoxane 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 apparently quite specific in protecting against lesions after s.c. doxorubicin and daunorubicin.
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