Annals of Oncology 12:405-410, 2001
© 2001 European Society for Medical Oncology
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Dexrazoxane is a potent and specific inhibitor of anthracycline induced subcutaneous lesions in mice
1Laboratory of Experimental Medical Oncology, Copenhagen University Hospital Denmark
2Finsen Center, Laboratory Center, Copenhagen University Hospital Denmark
Correspondence to:S. W. Langer, MD, The Laboratory of Experimental Medical Oncology, The Finsen Center 5073, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark, E-mail: swlanger{at}dadlnet.dk
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 tripletreatment 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.
anthracycline, catalytic inhibitor, dexrazoxane (ICRF-187), extravasation, free radical scavenger, topoisomerase II
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