Anthracycline

• Anthracyclines are a class of antineoplastic agents widely used in the treatment of various types of cancer. They are characterized by their distinctive chemical structure and exhibit potent anticancer activity.
• Anthracyclines work by interfering with the replication and transcription of DNA, ultimately leading to the inhibition of tumor growth.

Anthracycline mechanism2

Mechanism of Action

• Anthracyclines exert their anticancer effects through multiple mechanisms:

DNA Intercalation:

• Anthracyclines intercalate into the DNA helix, causing structural distortions and inhibiting proper DNA replication and transcription.
• This interference disrupts cellular processes essential for tumor growth.

Topoisomerase II Inhibition:

• Anthracyclines inhibit the activity of topoisomerase II, an enzyme involved in DNA unwinding and repair.
• By preventing topoisomerase II from completing its function, anthracyclines induce DNA damage and hinder cancer cell proliferation.

Generation of Free Radicals:

• Anthracyclines can undergo redox reactions, generating free radicals that can cause oxidative stress and damage cellular components, including DNA and proteins.
• This oxidative stress contributes to the cytotoxic effects of anthracyclines on cancer cells.

Examples of Anthracyclines

Some commonly used anthracyclines include:

• Doxorubicin (Adriamycin)
• Daunorubicin (Cerubidine)
• Epirubicin (Ellence)
• Idarubicin (Idamycin)
• Mitoxantrone (Novantrone)

• These medications may differ in terms of their potency, administration route, dosage, and potential side effects.
• The choice of anthracycline depends on the specific cancer type, stage, and individual patient factors.

Clinical Uses

Anthracyclines are used in the treatment of various malignancies, including:

• Breast Cancer: Anthracyclines, such as doxorubicin and epirubicin, are commonly included in combination chemotherapy regimens for both early-stage and advanced breast cancer.
• Lung Cancer: Anthracyclines are used in the treatment of certain types of lung cancer, either as part of combination chemotherapy or in specific cases where other treatment options are limited.
• Lymphomas: Anthracyclines, particularly doxorubicin, are an integral component of chemotherapy regimens for Hodgkin lymphoma and various forms of non-Hodgkin lymphoma.
• Leukemias: Anthracyclines, such as daunorubicin and idarubicin, are used in the treatment of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).
• Sarcomas: Anthracyclines, often in combination with other agents, are utilized in the treatment of soft tissue sarcomas and certain types of bone sarcomas.

Side Effects

The use of anthracyclines can be associated with several potential adverse effects:

• Cardiotoxicity: Anthracyclines have the potential to cause cardiotoxicity, leading to heart muscle damage and impaired cardiac function. The risk of cardiotoxicity increases with cumulative dose and may manifest as cardiomyopathy, arrhythmias, or heart failure.
• Myelosuppression: Anthracyclines can suppress the production of blood cells in the bone marrow, resulting in decreased red blood cells (anemia), white blood cells (neutropenia), and platelets (thrombocytopenia). This can increase the risk of infections, bleeding, and fatigue.
• Gastrointestinal Effects: Anthracyclines may cause nausea, vomiting, diarrhea, and mucositis (inflammation of the mucous membranes), which can impact a patient's nutritional status and quality of life.
• Hematologic Malignancies: Long-term use of anthracyclines has been associated with a small risk of developing secondary hematologic malignancies, such as acute leukemia or myelodysplastic syndrome.

Precautions and Monitoring

• When prescribing anthracyclines, healthcare providers should consider the following precautions and monitoring strategies:
• Baseline cardiac assessment, including evaluation of cardiac function and electrocardiogram (ECG), should be performed before initiating anthracycline therapy. Regular monitoring of cardiac function, such as echocardiography or multigated acquisition (MUGA) scan, may be necessary during treatment.
• Anthracyclines have a cumulative lifetime dose limit due to the risk of cardiotoxicity. Monitoring the cumulative dose and considering alternative treatment options may be necessary when approaching the maximum allowable dose.
• Regular blood cell counts should be performed to monitor for myelosuppression. Adjustments in the dosage or treatment schedule may be needed to manage hematologic toxicity.
• Patients should receive comprehensive education about the potential side effects, proper self-care measures, and the importance of adherence to treatment.

Contraindications:

• Anthracyclines, have certain contraindications, meaning that their use is not recommended or should be avoided in specific situations.

• Here are some common contraindications associated with anthracyclines:

Known Hypersensitivity: Individuals with a known hypersensitivity or severe allergic reaction to anthracyclines or any of their components should not receive these medications.

• Severe Cardiac Disease: Anthracyclines can have cardiotoxic effects and may worsen pre-existing heart conditions, such as congestive heart failure, cardiomyopathy, or severe arrhythmias. In such cases, the use of anthracyclines is generally contraindicated. Close monitoring of cardiac function is essential before and during treatment.

• Active Infection: Anthracycline therapy may further suppress the immune system and increase the risk of infections. It is generally contraindicated to administer anthracyclines in the presence of an active infection, especially if it is severe.

• Pregnancy and Breastfeeding: Anthracyclines can be harmful to developing fetuses and should be avoided during pregnancy. These medications may also be excreted in breast milk and could harm nursing infants. Adequate contraception should be used during anthracycline treatment, and breastfeeding should be discontinued.

• Severe Hepatic Dysfunction: Anthracyclines are primarily metabolized in the liver, and severe hepatic dysfunction can impair their clearance, leading to increased toxicity. In such cases, the use of anthracyclines may be contraindicated or require dosage adjustments.

• Previous Maximum Cumulative Dose Reached: Anthracyclines have a cumulative dose limit due to the risk of cardiac toxicity. If a patient has previously received the maximum cumulative dose of an anthracycline or if they have reached their lifetime dose limit, further administration of the same or similar anthracyclines may be contraindicated.

See Also

• Chemotherapy
• Cancer Treatment
• Cardiotoxicity
• Hematopoietic Stem Cell Transplantation
• Oncology Nursing
• Supportive Care in Cancer

References

• National Cancer Institute. (2021). Anthracyclines.
• Lexicomp Online. Anthracyclines (Doxorubicin, Daunorubicin, Epirubicin, Idarubicin, Mitoxantrone) - Drug Information.
• UpToDate. (2022). Anthracyclines: Dosing and toxicity management.

• Dailymed label info on Anthracycline
• FDA Anthracycline