Cytostatic antibiotics of the
anthracycline class are the best known of the chemotherapeutic agents that cause
cardiotoxicity.
Alkylating agents such as
cyclophosphamide,
ifosfamide,
cisplatin,
carmustine,
busulfan,
chlormethine and
mitomycin have also been associated with
cardiotoxicity. Other agents that may induce a
cardiac event include
paclitaxel,
etoposide,
teniposide, the
vinca alkaloids,
fluorouracil,
cytarabine,
amsacrine,
cladribine,
asparaginase,
tretinoin and
pentostatin.
Cardiotoxicity is rare with some agents, but may occur in >20% of patients treated with
doxorubicin,
daunorubicin or
fluorouracil.
Cardiac events may include mild blood pressure changes,
thrombosis, electrocardiographic changes, arrhythmias,
myocarditis,
pericarditis,
myocardial infarction,
cardiomyopathy,
cardiac failure (left ventricular failure) and
congestive heart failure. These may occur during or shortly
after treatment, within days or weeks
after treatment, or may not be apparent until months, and sometimes years, after completion of
chemotherapy. A number of risk factors may predispose a patient to
cardiotoxicity. These are: cumulative dose (
anthracyclines,
mitomycin); total dose administered during a day or a course (
cyclophosphamide,
ifosfamide,
carmustine,
fluorouracil,
cytarabine); rate of administration (
anthracyclines,
fluorouracil); schedule of administration (
anthracyclines); mediastinal radiation; age; female gender; concurrent administration of
cardiotoxic agents; prior
anthracycline chemotherapy; history of or pre-existing cardiovascular disorders; and
electrolyte imbalances such as hypokalaemia and hypomagnesaemia. The potential for
cardiotoxicity should be recognised before
therapy is initiated. Patients should be screened for risk factors, and an attempt to modify them should be made. Monitoring for
cardiac events and their treatment will usually depend on the signs and symptoms anticipated and exhibited. Patients may be asymptomatic, with the only manifestation being electrocardiographic changes. Continuous cardiac monitoring, baseline and regular electrocardiographic and echocardiographic studies,
radionuclide angiography and measurement of serum
electrolytes and cardiac
enzymes may be considered in patients with risk factors or those with a history of
cardiotoxicity. Treatment of most
cardiac events induced by
chemotherapy is symptomatic. Agents that can be used prophylactically are few, although
dexrazoxane, a
cardioprotective agent specific for
anthracycline chemotherapy, has been approved by the US Food and Drug Administration.
Cardiotoxicity can be prevented by screening and modifying risk factors, aggressively monitoring for signs and symptoms as
chemotherapy is administered, and continuing follow-up after completion of a course or the entire treatment. Prompt measures such as discontinuation or modification of
chemotherapy or use of appropriate
drug therapy should be initiated on the basis of changes in monitoring parameters before the patient exhibits signs and symptoms of
cardiotoxicity.