TY - JOUR

T1 - Dexrazoxane is a potent and specific inhibitor of anthracycline induced subcutaneous lesions in mice

AU - Langer, S W

AU - Sehested, M

AU - Jensen, P B

PY - 2001/3

Y1 - 2001/3

N2 - 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.

AB - 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.

KW - Animals

KW - Antibiotics, Antineoplastic/antagonists & inhibitors

KW - Antineoplastic Agents/pharmacology

KW - Area Under Curve

KW - Dose-Response Relationship, Drug

KW - Enzyme Inhibitors/pharmacology

KW - Extravasation of Diagnostic and Therapeutic Materials/complications

KW - Female

KW - Mice

KW - Razoxane/pharmacology

KW - Topoisomerase II Inhibitors

KW - Ulcer/chemically induced

U2 - 10.1023/a:1011163823321

DO - 10.1023/a:1011163823321

M3 - Journal article

C2 - 11332155

VL - 12

SP - 405

EP - 410

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 3

ER -