Treatment of anthracycline extravasation in mice with dexrazoxane with or without DMSO and hydrocortisone.
Dexrazoxane has been reported to be protective against anthracycline induced subcutaneous ulceration in mice. It is currently under clinical investigation as an acute antidote in accidental anthracycline extravasation, for which indication topical dimethylsulfoxide (DMSO) and intralesional hydrocortisone are used empirically. We studied the effect in 72 mice of monotherapy with and combined therapy of intraperitoneal dexrazoxane, topical DMSO, and intralesional hydrocortisone as acute antidotes against ulceration after subcutaneous daunorubicin. Dexrazoxane completely prevented wounds from occurring, while neither DMSO nor hydrocortisone had any preventive effect. The addition of topical DMSO actually reduced the efficacy of dexrazoxane. In conclusion, the present study does not support the concomitant use of topical DMSO + systemic dexrazoxane or intralesional hydrocortisone + systemic dexrazoxane. Monotherapy with systemic dexrazoxane seems preferable and is highly efficacious in preventing ulceration.
Laboratory of Experimental Medical Oncology, The Finsen Center 5073, Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark. swlanger@dadlnet.dk
Seppo W
SW
Langer
Annemette V
AV
Thougaard
Maxwell
M
Sehested
Peter Buhl
PB
Jensen
D000287:Administration, Topical; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D003630:Daunorubicin / Q000009:adverse effects*; D004121:Dimethyl Sulfoxide / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D006854:Hydrocortisone / Q000008:administration & dosage / Q000627:therapeutic use*; D015552:Injections, Intralesional; D007274:Injections, Intraperitoneal; D051379:Mice; D008815:Mice, Inbred Strains; D011929:Razoxane / Q000008:administration & dosage / Q000627:therapeutic use*
D000903:Antibiotics, Antineoplastic; D011929:Razoxane; D006854:Hydrocortisone; D004121:Dimethyl Sulfoxide; D003630:Daunorubicin