Abstract
Anthracyclines (ATCs) have a great efficacy against many types of cancer and is currently
considered a cornerstone in the treatment of numerous pediatric and adult hematological
and solid tumors. Great advances have been achieved after the entry of ATC group into
the cancer treatment in the early 1960s, and the overall survival ratio has increased
from 30% to near 70%. Due to their significant role and great value in cancer therapy,
which is persistent to date, ATCs are listed in the World Health Organization model
list of essential medicines. The clinical use of ATC such as doxorubicin and daunorubicin
can be viewed as a sort of double-edged sword. On the one hand, ATCs play an undisputed
key role in the treatment of many neoplastic diseases; on the other hand, the administration
of ATC is associated with the risk of severe adverse effects. The most common side
effect of the ATC group is cardiotoxicity (CTX), which may limit its use and increases
mortality and morbidity rates. The clinical use of ATC is limited by unique maximum
total cumulative dose (approximately 350 mg/m2) limiting CTX. ATC CTX is cumulative dose-dependent and is in most of the occasions
irreversible. Lowering the cumulative dose has been proved to be useful in minimize
the risk of heart failure (HF), but, yet, there is a growing concern that HF might
occur following doses that were thought to be safe. The average incidence of HF is
around 5% at a cumulative dose of 400 mg/m2 that becomes higher above 500 mg/m2, albeit with substantial individual variation. The newer generations ATC medications
such as epirubicin, idarubicin, and mitoxantrone were thought to be safer; however,
subsequent clinical studies showed more or less similar toxicity profiles. The use
of cardioprotective agents (e.g., dexrazoxane and amifostine) has been associated
with improved safety range; however, questions are looming on their effect on ATC
antitumor effects. An overwhelming amount of clinical evidence suggests that ATCs
are too good to be old. Yet, they would look much better if they caused less harm
to the heart when administered as either single agents or in combination with otherwise
promising new drugs. In this review article, we present a comprehensive account on
the ATC and provide up to date data on their clinical use and toxicity profile. In
addition, we provide a contemporary approach on the early detection, diagnosis, and
treatment of ATC CTX.
Keywords
Anthracyclines - cardiac failure - daunorubicin - dexrazoxane - doxorubicin
