Dexrazoxane efficacy for anthracycline extravasation: use in UK clinical practice

Abstract

Extravasation is recognised as a major complication of administering intravenous chemotherapy treatment. Of the agents involved in extravasation, anthracyclines are associated with the greatest risk to patients because they are vesicant agents, having the potential to cause blistering and ulceration. If not identified and left untreated, anthracycline extravasation can lead to more serious complications such as tissue necrosis and functional impairment. Dexrazoxane (Savene(®) ) is the only licensed antidote for the treatment of anthracycline extravasation and clinical evidence has shown Savene(®) to be highly effective for preventing the need for surgery following anthracycline extravasation, allowing full recovery in the majority of patients. To date, there have been eight published studies reporting a total of 102 cases of Savene(®) use. Here, we review the published data on the efficacy of Savene(®) and present an analysis of 12 UK case studies. All UK oncology centres where Savene(®) has been used to manage anthracycline extravasation were contacted by SpePharm UK, who requested case studies for this publication. All of the cases received, including two from our own experience of using Savene(®) have been included in the analysis.

Complete Recovery of a Wide Local Reaction by the Use of Dexrazoxane 72 Hours after Epirubicin Extravasation: Case Report and Review of the Literature

“…As vesicants, anthracyclines are capable of inducing massive and long-lasting tissue injuries and blistering formations when extravasated [4,8]. Over several weeks, tissue destruction may progress and, in the worst case, severe necrosis and ulceration may eventually lead to an amputation [4,8,11].…”

“…Furthermore, the pharmacological mechanisms of the bisdioxopiperazine dexrazoxane are not completely understood [7,11]. Several authors have suggested that due to the building of chelates as a metal ion chelator it may, firstly, prevent the formation of free radicals and, secondly, inhibit reversibly topomerase II, therefore working as a protective agent [1,3,7,8,10,11]. The recommended 3-day treatment schedule consists of a daily dose of 1,000 mg/m 2 on the 1st and 2nd days and 500 mg/m 2 on the 3rd day given once [1,2,4,5].…”

“…In the case of renal impairment, the dose has to be reduced accordingly [11]. It is recommended to administer dexrazoxane within the first 6 h in the unaffected arm [2,4,5,8,9,10,11]. Several reports have described successful treatment with the use of dexrazoxane when administered within hours (ranging from 4 to 5 h) after the extravasation [2,3,5,7,11].…”

“…Several reports have described successful treatment with the use of dexrazoxane when administered within hours (ranging from 4 to 5 h) after the extravasation [2,3,5,7,11]. Recently, Muthuramalingam et al [8] summarized 12 cases of anthracycline extravasation that were treated with dexrazoxane in the UK. The time to first infusion after the incident ranged from 40 min to 4 h and 10 min.…”

“…Until recently, no effective conservative treatment had been described for the dreaded accidental anthracycline extravasation [4]. Nowadays, immediate treatment with dexrazoxane, the only proven antidote in the case of accidental anthracycline extravasation, has been implemented into daily clinical practice [1,4,5,7,8]. Despite topical DMSO, it is the recommended specific antidote to be used as soon as possible (ideally not after 6 h) after anthracycline extravasation, as mentioned in the ESMO-EONS guidelines [9].…”