Treatment of anthracycline extravasation with Savene (dexrazoxane): results from two prospective clinical multicentre studies.
BACKGROUND
The purpose of this study was to assess the efficacy and tolerability of i.v. dexrazoxane [Savene (EU), Totect (US)] as acute antidote in biopsy-verified anthracycline extravasation.


METHODS
Two prospective, open-label, single-arm, multicentre studies in patients with anthracycline extravasation were carried out. Patients with fluorescence-positive tissue biopsies were treated with a 3-day schedule of i.v. dexrazoxane (1000, 1000, and 500 mg/m(2)) starting no later than 6 h after the incident. Patients were assessed for efficacy (the possible need for surgical resection) and toxicity during the treatment period and regularly for the next 3 months.


RESULTS
In 53 of 54 (98.2%) patients assessable for efficacy, the treatment prevented surgery-requiring necrosis. One patient (1.8%) required surgical debridement. Thirty-eight patients (71%) were able to continue their scheduled chemotherapy without postponement. Twenty-two patients (41%) experienced hospitalisation due to the extravasation. Mild pain (10 patients; 19%) and mild sensory disturbances (nine patients; 17%) were the most frequent sequelae. Haematologic toxicity was common as expected from the fact that the extravasation occurred during a chemotherapy course. Other toxic effects were transient elevation of alanine aminotransferases, nausea, and local pain at the dexrazoxane injection site.


CONCLUSIONS
Dexrazoxane proved to be an effective and well-tolerated acute treatment with only one out of 54 assessable patients requiring surgical resection (1.8%).
Mouridsen
H T
HT
Department of Oncology, Copenhagen University Hospital, Denmark.
Langer
S W
SW
Buter
J
J
Eidtmann
H
H
Rosti
G
G
de Wit
M
M
Knoblauch
P
P
Rasmussen
A
A
Dahlstrøm
K
K
Jensen
P B
PB
Giaccone
G
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000009:adverse effects*; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D003646:Debridement; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005060:Europe; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D009336:Necrosis / Q000517:prevention & control / Q000601:surgery; D011446:Prospective Studies; D011929:Razoxane / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D059005:Topoisomerase II Inhibitors; D016896:Treatment Outcome
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D004791:Enzyme Inhibitors; D059005:Topoisomerase II Inhibitors; D011929:Razoxane; D004250:DNA Topoisomerases, Type II