Anthracycline Drugs for Chemo: How Do They Work?

Anthracycline chemotherapy drugs are potent cancer treatments derived from Streptomyces bacteria. These drugs work by binding to cancer cell DNA, preventing replication and stopping tumor growth. Commonly used for breast cancer, leukemia, and lymphomas, anthracyclines are among the most effective chemotherapy drugs available.

What are anthracycline chemotherapy drugs?

Anthracyclines are a group of medications made from certain types of Streptomyces bacteria. They are used to treat several types of cancer by damaging cancer cell DNA. They are considered effective cancer treatments since they disrupt cancer cell replication and processes essential for their survival.

What cancers are treated with anthracyclines?

Anthracyclines are used to treat many different types of cancer. Cancers that are FDA approved to be treated with anthracyclines include:

• Acute lymphocytic leukemia
• Acute myelogenous leukemia
• Hodgkin's lymphoma
• Non-Hodgkin's lymphoma
• Bladder cancer
• Breast cancer
• Metastatic ovarian cancer
• Metastatic osteogenic sarcoma
• Metastatic Ewing sarcoma
• Metastatic soft tissue sarcoma
• Metastatic thyroid cancer
• Metastatic neuroblastoma
• Metastatic Wilms tumor
• Metastatic small cell lung cancer

In addition to the FDA-approved indications listed above, anthracyclines are also used off-label to treat other types of cancers. These may include metastatic liver cancer, multiple myeloma, and certain types of advanced kidney cancers.

How do anthracycline chemotherapy drugs work?

Anthracyclines work by damaging DNA in cancer cells, which causes them to die. Researchers have identified a number of mechanisms that explain how these potent medications work. Some ways anthracyclines work to kill cancer cells are:

1. Interacting with a protein called topoisomerase-II, which prevents healing of DNA breaks. This prevents cancer cells from growing, and leads to apoptosis (programmed cell death).
2. Inserting between base pairs of DNA, which stops DNA and RNA synthesis in rapidly-dividing cells and blocks cancer cells from dividing. This is called DNA intercalation.
3. Generating reactive oxygen species that damage DNA and cell membranes, leading to cell apoptosis.

Common anthracycline drugs used in cancer treatment

There are many different anthracycline drugs that are used in cancer treatment. Each one is approved for specific types of cancer. Chemotherapy drugs that belong to the anthracycline drug class include:

• Daunorubicin - leukemia treatment
• Doxorubicin (Adriamycin, Doxil) - ovarian cancer, sarcoma, multiple myeloma, breast cancer, leukemia, lymphoma, Wilms tumor, neuroblastoma, bladder cancer, thyroid cancer, stomach cancer, and lung cancer treatment
• Epirubicin (Ellence) - treatment of axillary node tumor involvement following resection of primary breast cancer
• Idarubicin (Idamycin PFS) - acute myeloid leukemia treatment
• Mitoxantrone - prostate cancer and acute nonlymphocytic leukemia treatment
• Valrubicin (Valstar) - bladder cancer treatment

What are the side effects of anthracycline chemo?

While their efficacy in cancer management is well-established, the use of anthracycline chemotherapy is complicated by a spectrum of side effects, ranging from acute toxicities to delayed, life-threatening complications.

Common side effects of anthracycline chemotherapy drugs include:

• Chills
• Hives
• Itching
• Nausea and vomiting
• Hair loss
• Fatigue
• Diarrhea
• Fever
• Mucositis
• Stomach pain
• Low appetite

More serious side effects may include cardiotoxicity (heart damage), lung damage, cognitive deficits, secondary cancers, blood clots, low blood cell counts, severe allergic reactions, heart failure, stomach bleeding, liver damage, tissue injury where the medication is administered, and seizures. Some side effects may be permanent.

Anthracyclines might cause harm to babies when taken during pregnancy. Tell your healthcare provider if you become pregnant while taking this medication. Females taking anthracyclines have experienced premature menopause, and they can also damage sperm in males.

Your healthcare provider can order lab tests to monitor you for side effects from anthracycline chemotherapy. In some cases, they may need to delay or reduce your dose until your body recovers. To lower your risk of long-term side effects, anthracyclines have maximum recommended lifetime cumulative doses that should not be exceeded.

How can heart damage from anthracyclines be prevented?

Damage to the heart is a serious side effect that can happen from anthracyclines due to the generation of reactive oxygen species. The heart muscle can get damaged, which can affect heart function and potentially lead to heart failure. Symptoms of heart damage can occur at any time during or after anthracycline chemotherapy. Your healthcare provider will monitor your heart health by ordering tests such as multi-gated radionuclide angiography, echocardiograms, and electrocardiograms.

Certain medications can interact with anthracycline chemotherapy and raise your risk for side effects, including cardiotoxicity. Examples include medications that block certain proteins in the liver that normally break down the anthracycline called CYP3A4 and CYP2D6 inhibitors. Tell your healthcare provider about all of the medications you are taking so they can check for interactions.

Dexrazoxane is a cardioprotective drug that is FDA approved to reduce the severity of heart damage due to doxorubicin in females with metastatic breast cancer. It is thought to work by interfering with free radical generation. It is given as an intravenous infusion just before a dose of doxorubicin.

Liposomal anthracyclines were developed to reduce toxic effects. These formulations have been shown to cause less heart damage and stomach side effects compared to conventional formulations.

Make sure to discuss all possible risks and benefits of anthracycline chemotherapy for your specific cancer with your healthcare provider. They can also talk with you about alternative treatment options.