Causes, Diagnosis, and Treatment of Extravasation - the European ...

• Marked induration, often brownish, lasting for days to months withskin atrophy.• Invasive ulceration which may occur after 1-4 weeks andprogressively enlarges in size extending to deep tissue structureswhere anthracycline can persist for months. This occurs in aboutone third of patients experiencing an anthracycline extravasationwhich is not appropriately recognised and treated.• Long-term pain, contractures, dystrophy, and potential loss offunction of the affected limb.Immediate Treatment MeasuresPrompt intervention is mandatory if an anthracycline extravasation issuspected. First the infusion should be discontinued, the residual drugshould be aspirated without applying pressure to the injection site, asaline flush should not be used, the venous access device should beremoved, and the extremity should be elevated and local cooling shouldbe applied. If treatment with SaveneTM (dexrazoxane) is the standard ofpractice, then the affected area should not be cooled during SaveneTMinfusion. The site of extravasation should be marked and theextravasated volume should be estimated. Appropriate documentationof the event is essential.Treatment ApproachesSo far, there have been no uniformly accepted guidelines regardingtreatment for extravasation of anthracyclines. However, many hospitalshave developed their own guidelines for the management of thisadverse event. Single or combined application of cooling and thetopical use of corticosteroids or DMSO are the most commonly usedtreatment approaches for extravasation of a vesicant. When managedusing conventional techniques, the outcome of anthracyclineextravasation is typically poor, with many patients experiencing serioussequelae as a result of the extravasation or subsequent surgery.Surgery has proven to be effective if performed at the optimal time, butsince anthracyclines can persist in the lesion for weeks to months, thesurgical procedure must be extensive and can lead to large defectswhich require skin grafting.Systemic Treatment of an ExtravasationLast year, SaveneTM, an antidote for anthracycline extravasationdamage, was approved by the European Medicines Agency (EMEA). Twoclinical trials provided evidence for the efficacy of SaveneTM . In thesetrials, SaveneTM provided protection from the damage caused by theanthracycline extravasation thereby sparing the patient from surgicalinterventions. SaveneTM should be used as soon as possible but nolater than 6 hours following the extravasation. It should not becombined with DMSO which could diminish its effectiveness andcooling should be discontinued 15 minutes prior to administration.The most common side effects experienced by patients who receivedSaveneTM were nausea and haematological toxicity (5) . Therecommended dosing regimen is 1000mg/m_ on Day 1 and Day 2 and500 mg/m_ on Day 3. SaveneTM is administered per IV infusion over1 to 2 hours in a larger contralateral vein and repeated after 24 h and48 h.SummaryThe consequences of anthracycline extravasation represent asignificant risk in the treatment of cancer. Even though anthracyclineextravasation is rare, it may have potentially serious immediate andlonger-term effects. Systemically administered Savene may protectpatients against the potentially devastating effects of extravasation.This article is the first in a series which focuses on anthracyclineextravasations. Future articles will focus on specific patient cases ofanthracycline extravasations and the presentation of guidelines foranthracycline extravasation developed by EONS members.References1. Stanley M. Managing complications of chemotherapy. The CytotoxicsHandbook, 3rd edition 1997.2. Brothers T.E. et al. Experience with Subcutaneous Infusion Ports in300 Patients. Surgery Gynecology & Obstetrics 1988; 166: 295-301.3. Lemmers N.W.M.et al. Complications of venous access ports in 132patients with disseminated testicular cancer treated withpolychemotherapy. Journal of Clinical Oncology 1996; 14: issue 11.4. Brown D.F. et al. Mode of chemotherapy does not affectcomplications with an implantable venous access device. Cancer1997; 80: issue5. Mouridsen H et al. Treatment of anthracycline extravasation withSavene (dexrazoxane): results from two prospective multicenterstudies. Ann Oncol 2007; 18: 546-550.Images of extravasation before and afteradministration of Savene. The left image showsswelling and redness at the site of infusion, whilethe right image shows the same area followingadministration of Savene (TopoTarget, data onfile from clinical trials).NEWSLETTER SPRING 2007 -23