Section IX: Medications

In patients receiving doxorubicin chemotherapy, monitoring of cardiac function is based upon baseline left ventricular function and total chemotherapy dosage received.

HPI: Patient with acute lymphoblastic leukemia, Hodgkin lymphoma, breast, bladder, stomach, or recurrent small cell lung cancer receiving chemotherapy with doxorubicin.

PMH: Congestive heart failure, hypertension, coronary artery disease.

SH: Alcohol.

Dyspnea, rales, tachycardia, jugular–venous distention, hepatomegaly, lower extremity edema.

Acute toxicity: Arrhythmias, electrocardiographic abnormalities, a pericarditis–myocarditis syndrome, and ventricular dysfunction during or immediately after administration of anthracyclines.

Early toxicity: Observed as dose-related occurrence of CHF in patients that received 500–550 mg/m² of doxorubicin.

Late toxicity: The onset of symptomatic CHF can occur as late as 10–12 years after the last anthracycline dose. Late CHF is due to a nonischemic dilated cardiomyopathy.

ECHO: LVEF <40%, LA and LV enlargement, wall motion abnormalities.

Radionuclide angiography (RNA): Monitoring changes in diastolic left ventricular function may identify evidence of cardiotoxicity earlier than monitoring ejection fraction, which is a marker of systolic function.

B4DOX = Before patient receives DOXorubicin or prior to administration of 100 mg/m² of doxorubicin.

PTDOX = PaTient has already received >100 mg/m² DOXorubicin.

EF-EVAL = Refer patient for echocardiogram, radionuclide angiography, or other imaging test for left ventricular Ejection Fraction EVALuation.

LVEF-OK = LVEF normal or if follow-up study shows decline in less than 10% from baseline study and absolute EF ≥30%.

LVEF<30 = LVEF <30%.

DECL-10 = LVEF DECLines by 10% from baseline study.

DC-DOX = DisContinue DOXorubicin.

CON-DOX = CONtinue DOXorubicin.

FU-#1 = Follow-Up study #1 with EF-EVAL at 300 mg/m². Repeat EF-EVAL at 400 mg/m² if patient has history of cardiomyopathy, radiation exposure, and abnormal electrocardiographic results, or is on cyclophosphamide therapy.

FU-#2 = Follow-Up study #2 with EF-EVAL at 450 mg/m².

FU-#3 = Follow-Up study #3 with EF-EVAL prior to each dose after 450 mg/m².

B4DOX = EF-EVAL

FU-#1 = EF-EVAL

FU-#2 = EF-EVAL

FU-#3 = EF-EVAL

PTDOX + LVEF-OK = CON-DOX

PTDOX + LVEF<30 = DC-DOX

PTDOX + DECL-10 = DC-DOX

The mechanism of doxorubicin cardiomyopathy may be due to the generation of free radicals and oxidative stress causing subcellular changes in the myocardium leading to loss of myofibrils and vacuolization of myocardial cells.

• – Endomyocardial biopsy has the highest sensitivity and specificity for the diagnosis of doxorubicin-induced cardiomyopathy.

• – Patients with age >65 years are predisposed to cardiotoxicity at lower cumulative doses of doxorubicin.

1. Singal PK. Doxorubicin-induced cardiomyopathy. N Engl J Med. 1998;339:900–905.

2. Schwartz RG, McKenzie WB, Alexander J, et al. Congestive heart failure and left ventricular dysfunction complicating doxorubicin therapy. Am J Med.1987;82(6):1109–1118.

3. Lee BH, Goodenday LS, ...