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Supportive Oncology
A Focus on the Treatment of Anthracycline Extravasation and Tissue Protection
Seppo W Langer, MD, PhD,
1
Maxwell Sehested, MD, PhD
2
and Peter Buhl Jensen, MD, PhD
1
1. Consultant Medical Oncologist, Department of Oncology; 2. Consultant Pathologist, Copenhagen University Hospital
Abstract
Accidental extravasation of anthracycline-based chemotherapy is a complication that has been feared since the introduction of the
anthracyclines more than 40 years ago. Tissue infiltration with vesicant drugs may lead to progressive necrosis and destruction of muscles,
tendons, nerves, and joints, and may be associated with severe functional and cosmetic changes. During the last four decades, much effort has
been made to prevent such accidents from happening. In addition, different surgical approaches and several non-pharmacolgical and
pharmacological treatments have been used to counteract the devastating effects of the extravasation. Most treatment modalities have been
empirically based, and only a few have undergone thorough evaluation. Recently, dexrazoxane was shown to be an effective and non-toxic
acute treatment for anthracycline extravasation. It has since become a widely recommended treatment, and Totect
®
is currently the only
approved drug for this indication.
Keywords
Anthracycline, extravasation, dexrazoxane, tissue protection, doxorubicin, Totect
Disclosure: Seppo W Langer, MD, PhD, has recieved consultant honoraria from TopoTarget, Maxwell Sehested is CSO of TopoTarget, and Peter Buhl Jensen, MD, PhD, is CEO of TopoTarget.
Received: February 8, 2009 Accepted: April 20, 2009
Correspondence: Seppo W Langer, MD, PhD, Department of Oncology, Section 5073, Copenhagen University Hospital, Rigshospitalet, DK-2100 Copenhagen, Denmark.
E: seppo.langer@rh.regionh.dk
Anthracycline Extravasation scheduled antineoplastic treatment, as well as long-term cosmetic
For 40 years, the use of anthracycline anticancer drugs has been a and functional defects.
7,9,10
mainstay in the curative and palliative treatment of many solid tumors
and hematological malignancies. Millions of patients have received Prevention
treatment with doxorubicin, epirubicin, daunorubicin, and several Following the initial descriptions in the 1970s of progressive
newer analogs. Regrettably, a small fraction of patients have suffered ulceration and destruction of deeper neurovascular or tendon
from the unintentional extravasation of these drugs, which is a structures, it became clear that every precaution should be taken to
potentially devastating complication. prevent extravasations.
11,12
Intense surveillance by the treating nurse
during anthracycline infusion has since then been routinely carried
After the unintended leakage into the peri-vascular tissues, the clinical out in most oncology institutions.
13
Other preventive measures
course is characterized by redness and swelling. Pain may be present, include the use of central venous access devices that may reduce the
but is not mandatory for diagnosis. Within days to weeks, blisters, risk for extravasation; however, this does not completely eliminate
ulceration, and necrosis may occur, and the tissue destruction may the risk.
continue into adjacent areas. Anthracyclines have a propensity to
persist in tissues for months.
1,2
Accordingly, the progressive tissue Surgical Treatment
destruction may continue for weeks and even months. There are no uniform guidelines for the surgical treatment of
anthracycline extravasations. It has generally been agreed that for
The tendency to form necrosis and ulceration depends in part significant extravasations, surgery should be performed to remove
on the amount and concentration of the anthracycline. Other factors the tissue-bound anthracycline. Often, only the timing of the
that may play a role are host factors such as the location and intervention has been open for discussion, i.e. early versus late
venous flow. Not all anthracycline extravasations develop into surgery.
3,4,9,12,14
During surgical excision, wide margins encompassing all
ulceration. However, for significant extravasations the risk is anthracycline-containing tissues are often adopted. The procedure
estimated to be 25–50%.
3–8
Unless treated, the complication may may be guided by fluorescence microscopy of margins, and may
cause short-term defects, infections, and discontinuation of the necessitate skin grafting.
4,5,9,15,16
The presence of blisters or severe pain
24 © TOUCH BRIEFINGS 2009
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