Anthracycline chemotherapy agents-include adriamycin and daunomycin among others.
Anthracyclines work in multiple ways, including intercalation between DNA base pairs and inhibition of type II topoisomerase function, resulting in inhibition of cell replication and transcription.
They also work by inhibition of DNA helicase, resulting in DNA cleavage.
Patients being considered for anthracycline based therapy should be screened for cardiotoxicity risk factors, including age, smoking history, obesity, comorbidities, use of other cardiotoxic agents, and prior chest radiotherapy.
Estimated that more than 70% of children treated with anthracyclines will develop some evidence of cardiotoxicity.
It is estimated that subclinical cardiac dysfunction occurs in 10-15% of the patients (Jones LW et al).
Adjuvant regimens typically use 240-360 mg per meter squared of doxorubicin or 240-720 mg to meter squared of epirubicin over 4-6 cycles and with these doses patients who developed a cardiac event within 5 years following completion of chemotherapy ranges from 0.5-to 1.5% (Trudeau M et al).
Cardiotoxicity related to cumulative dose, length of treatment, and young age at the time of drug exposure.
Cardiac imaging modalities, echocardiographic parameters, circulating biomarkers, such as troponin I, naturiuretic peptides and cardiomyocyte cell-free, DNA and circulating, micro RNA’s may allow for earlier identification of cardiomyocyte damage, before the onset of left ventricular dysfunction.
Cardiac events is about 4 times greater when trastuzumab is administered with the following an anthracycline.
Females have a greater risk of cardiotoxicity.
Children at greater risk for cardiotoxicity than adults.
Young girls have significant increase in cardiotoxicity risk.
Cancer survivors exposed to anthracyclines have an increased risk of myocardial infarction, stroke and CHF.
Aortic stiffness occurs within 4 months of exposure to anthracyclines (Chaosuwannakit N).
Risk for cardiotoxicity related to cumulated dose administered, pre-existing heart disease, history of prior mediastinal radiation, and co-administration trastuzumab, paclitaxel and desrazoxane (Schapiro CL).
SEER data reveals higher risks for CHF in women treated with anthracyclines age 66-70 than for those treated with regimens without anthracyclines (Pinder MC).
When used in adjuvant chemotherapy for breast cancer demonstrates improvement over chemotherapy without such agents as far as recurrence rate, death rate and 5-year survival rate.
Toxicities include myelosuppression, alopecia, mucositis, nausea, vomiting, myocardial damage and extravasation reactions.
Incidence of leukemia associated with such agents range is between 0.4% and 1.7% 5-10 years following treatment(Trudeau M et al).
Additional toxicities include secondary leukemia and myelodysplastic, syndromes, infertility, early menopause, cognitive dysfunction and cancer related fatigue.
The increase in incidence of acute myelogenous leukemia with the use of anthracycline is an additional case per 700 women.
The increase in incidence of acute myelogenous leukemia with the use of anthracycline in early breast cancer is one additional case per 700 women.
Moderate doses of doxorubicin (adriamycin) can lead to cardiomyopathy with one study showing 39% of lymphoma patients treated with a mean cumulative dose of 300 mg/m2 with decreased left ventricular ejection fraction, without clinical signs of congestive heart failure.
Doxorubicin associated CHF related to advancing age, male sex, radiotherapy, and obesity.
Doxorubicin rapidly cleared from the circulation with widespread distribution may contribute to cardiomyopathy or late onset ventricular dysfunction.
When used in adjuvant chemotherapy for breast cancer demonstrates improvement over chemotherapy without such agents as far as recurrence rate, death rate and 5-year survival rate.
In adjuvant chemotherapy studies for breast cancer there is a decreased relative risk of recurrence and death by at least 25%.
There is only a 1% risk of clinical cardiotoxicity in patients receiving such agents.
Anthracycline chemotherapy agents-topoisomerase II is the major target of such agents.
May be beneficial only in breast cancer patients that over express HER2.
Cognitive impairment and brain changes occur patients with breast cancer treated exclusively with anthracycline containing regimens.
Treatment in patients with early breast cancer and adjuvant breast cancer revealed that the presence of chromosome 17 polysomy predicts improved response to such agents.
20-30% of breast cancers exhibit chromosome 17 polysomy and that suggests that 70 to 80% of women who are treated with an anthracycline in adjuvant fashion derive little or no benefit from it.
The national epirubicin trial indicated that amplification of HER2 or topoisomerase 2A were only moderately predictive for response to anthracycline as adjuvant therapy in breast cancer.
Patients who receive anthracycline based therapies may be at increased risk for memory problems and underlying brain injury and the affects persist several years beyond treatment conclusion.