COMPLICATIONS OF TREATMENT
Evaluating the role of dexrazoxane as a
cardioprotectant in cancer patients
receiving anthracyclines
Pierre Pouillart*
Institut Curie, 26 Rue d’Ulm, 75005 Paris, France
Summary Anthracyclines remain an important group of chemotherapeutic agents,
despite their inherent cardiotoxicity. This cardiotoxicity may be even more of a
concern in the future, as combination therapies of anthracyclines with newer agents
become routine. Such combinations may be highly effective, but cardiotoxicity may
also be increased. Dexrazoxane reduces the incidence of cardiotoxicity, as
demonstrated in numerous clinical trials in both adults and children. Evidence
from the literature suggests no effect of dexrazoxane on the antitumour efficacy of
anthracyclines, and there is no adverse effect on survival. Dexrazoxane is therefore
a valuable tool for oncologists using anthracycline-based regimens.
c
2004 Elsevier Ltd. All rights reserved.
KEYWORDS
Dexrazoxane;
Cardiotoxicity;
Anthracycline;
Doxorubicin;
Epirubicin;
Cardioprotectant;
Tumour;
Cancer;
Chemotherapy;
Congestive heart failure
Introduction
Anthracyclines have an important role in the
treatment of a variety of tumour types because of
their broad efficacy and generally acceptable tol-
erability.
1
Recent work on their use in combination
therapies (e.g. anthracycline plus taxane) suggests
an exciting future for these well established
drugs.
2–4
However, potentially lifethreatening
cardiotoxicity remains a problem with the anthra-
cyclines, and limits the cumulative dose that can
be administered.
Although several strategies have been evaluated
in attempts to reduce this cardiotoxicity, the only
consistently successful approach has been the use
of the cardioprotective drug dexrazoxane. The use
of dexrazoxane in some groups of patients receiving
anthracycline chemotherapy has previously been
questioned,
5
and this topic has generated inter-
esting debate.
6
This article attempts to identify the
scale of the cardiotoxicity problem with anthracy-
clines and to resolve some of the issues surrounding
the use of dexrazoxane. A medline search strategy,
primarily covering the years 1990–2003 was used to
review the publications associated with anthracy-
cline-induced cardiotoxicity. This strategy was not
intended to be an exhaustive literature analysis of
dexrazoxane publications, but an overview of the
most current studies in this therapy area.
New analyses of clinical data are pre-
sented, which further support the use of
dexrazoxane in conjunction with anthracycline-
based chemotherapy.
Cardiotoxicity of the anthracyclines
Five anthracyclines are in general use: doxorubicin,
epirubicin, daunorubicin, pirarubicin and idarubi-
* Tel.: +33-144-324-680; fax: +33-144-324-671.
E-mail address: pierre.pouillart@curie.net (P. Pouillart).
0305-7372/$ - see front matter
c
2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.ctrv.2004.06.002
CANCER TREATMENT REVIEWS (2004) 30, 643–650
www.elsevierhealth.com/journals/ctrv