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 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.


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.
Langer
S W
SW
Laboratory of Experimental Medical Oncology, Finsen Center, Copenhagen University Hospital, Denmark. swlanger@dadlnet.dk
Sehested
M
M
Jensen
P B
PB
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000970:Antineoplastic Agents / Q000494:pharmacology*; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000150:complications / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D005260:Female; D051379:Mice; D011929:Razoxane / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors; D014456:Ulcer / Q000139:chemically induced / Q000517:prevention & control
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D059005:Topoisomerase II Inhibitors; D011929:Razoxane