Adriamycin (Doxorubicin) Chemotherapy for Breast Cancer

Adriamycin (doxorubicin)—also known by the trade names Rubex and Doxil—is a chemotherapy drug that can slow or stop the growth of cancer cells. Adriamycin is commonly used to treat both early stage and metastatic breast cancer, usually in combination with other drugs.

More specifically, Adriamycin is a type of anthracycline antibiotic that is an anti-tumor drug and is made from the bacterium Streptomyces. It can be beneficial in cancer treatment because it can inhibit the activity of an enzyme called topoisomerase-II after entering cancer cells and inserting itself into the DNA structure. This action makes cells unable to reproduce themselves.

However, Adriamycin also forms oxygen free radicals, which damage cell membranes and proteins. It is one of the chemotherapy drugs likely to cause hair loss, and can also cause heart damage for some people.

In the context of breast cancer treatment, Adriamycin may be used for:

• Early-stage or node-positive breast cancer
• HER2-positive breast cancer
• Metastatic disease

Adriamycin is sometimes combined with Cytoxan (cyclophosphamide) and/or 5-fluorouracil to make a cocktail of breast-cancer-fighting chemotherapy drugs. The newer "double-dose" therapy uses a combination of high dose Adriamycin and Cytoxan in combination.

This drug is also approved by the U.S. Food and Drug Administration (FDA) for the treatment of other cancers, including:

• Ovarian cancer
• Bladder cancer
• Soft tissue cancer
• Osteogenic sarcoma
• Small cell lung cancer
• Thyroid cancer
• Gastric cancers
• Neuroblastoma
• Lymphoma
• Leukemia
• Wilms tumors
• Kaposi's sarcoma

Adriamycin is considered one of the preferred chemotherapy drugs for breast cancer.

According to a 2017 review of studies on the pegylated liposomal form (PLD), a phase 2 clinical study suggested that, after six cycles of PLD in combination with other drugs, remission was achieved in 71 percent of people with locally advanced or recurrent breast cancer. Similar studies suggested a 74 percent remission rate.

A 2014 study suggested that PLD along with Cytoxan (cyclophosphamide), Herceptin (trastuzumab), and Taxol (paclitaxel) for HER-2 positive locally advanced breast cancer achieved an effective rate of 83 percent.

The 2017 review cited above reports that in metastatic breast cancer, which is significantly harder to treat, PLD has had clinical trial success rates ranging from about 36 percent to 54 percent, depending on the trial and the combination of drugs used.

While effective, this medication does have a couple of factors working against it:

• Severe side effects (see below)
• Drug resistance

Because of the side effects, many people can't take it and others may be scared to try it. The drug resistance means that it's not effective against some tumors.

Liposomal and especially pegylated liposomal formulations appear to remain effective while lowering the risk of heart problems.

In addition, researchers are looking at other formulations that may improve the safety profile and decrease drug resistance, as well as drugs and supplements to pair with Adriamycin that allow for a lower dosage. According to a 2015 study published in the journal Scientific Reports, these include:

• Curcumin
• Interferon-alpha
• Quercetin
• Selenocystine
• Ocotillol

To help the drug more effectively kill cancer cells, a form of sugar called methyl beta-cyclodextrin (MCD) appears to be effective due to several mechanisms of action, according to the Scientific Reports paper.

Adriamycin is given by injection during a chemotherapy infusion. If the dose of Adriamycin that you are being given is very thick, it may be given as a "push" injection, rather than through an intravenous drip.

The drug will be delivered in a large plastic syringe, which will be attached to your catheter tubing. Your infusion nurse will slowly depress the plunger manually to inject the Adriamycin into your vein.

The adult dosage for breast cancer and several other forms of cancer is variable and can be any of the following:

• 60-75 mg/m(2) IV every 21 days
• 60 mg/m(2) IV every 14 days
• 40-60 mg/m(2) IV every 21-28 days
• 20 mg/m(2) per week

Side effects are common, though symptoms such as nausea and vomiting are often well controlled with preventive medications.

Side effects may include:

• Red-colored urine for two days after treatment (due to the drug's color, not bleeding)
• Hair loss or thin, brittle hair
• Nausea
• Vomiting
• Diarrhea
• Fatigue
• Mucositis (irritated mucous membrane in your mouth, stomach, and digestive tract)
• Amenorrhea (monthly menstrual cycle stops)
• Changes in nails (brittle or yellowed)

There are a number of risks related to Adriamycin, including:

• Allergic reaction
• Harm to the fetus, if you become pregnant during treatment
• Possible future infertility
• Low blood counts and greater danger of infections
• Chemotherapy-induced anemia (low red blood cell count)
• Thrombocytopenia (low platelet count)
• Heart damage, which is more common in women
• Skin damage: This can happen if the fluid leaks out and into your skin during infusion (extravasation). Talk to your oncologist about any redness, rashes, or tenderness near the infusion site.

Some of these risks, such as low blood counts (chemotherapy-induced neutropenia in particular) are common, and with double-dose therapy, your oncologist may recommend you receive a shot of Neulasta (pegfilgrastim), a drug to raise the white blood cell count, the day after your infusion.

Others risks, such as heart damage, are much less common overall.

The following drugs shouldn't be used along with Adriamycin because of potentially serious interactions:

• Gilotrif (afatinib)
• Erleada (apalutamide)
• Padaxa (dabigatran)
• Visimpro (dacomitinib)
• Ferriprox (deferiprone)
• Savasysa (edoxaban)
• Balversa (erdafitinib)
• Zydelig (idelalisib)
• Sporanox (itraconazole)
• Serzone (nefazodone)
• Ofev (nintedanib)
• Kepivance (palifermin)
• Pomalyst (pomalidomide)
• Epclusa (sofosbuvir/velpatasvir)
• Xeljanz (tofacitinib)
• Herceptin (trastuzumab)

The list of drugs that require close monitoring when combined with Adriamycin is extensive. Be sure you discuss everything you're taking—including over-the-counter drugs and nutritional supplements—with your doctor. It never hurts to double check with your pharmacist either.

People with the following conditions shouldn't be given this drug, or should be closely monitored while on it:

• Severe liver disease
• Severe myocardial insufficiency
• Recent myocardial infarction (the past four to six weeks)
• Severe, persistent, drug-induced myelosuppression
• Pregnancy

Because this drug can cause heart problems, you should have a MUGa scan, LVEF (left ventricular failure) test, or heart health evaluation done before starting treatment. This baseline exam will be used to compare with your heart function during and after treatment. Other tests for kidney and liver function may also be needed.

Your doctor will talk about what you need to do before and during Adriamycin treatment to ensure the infusion is as safe as possible.

It's important to:

• Use reliable contraception and avoid a pregnancy. Adriamycin can cause birth defects if given during the first trimester.
• Drink lots of fluids, especially water, to flush your kidneys and bladder.
• Avoid drinking alcohol and caffeine as these have a dehydrating effect that can dry out your tissues.
• Don't take aspirin, as it thins your blood.

If you have any of these symptoms while taking Adriamycin, call your doctor:

• Fever of 100.5 degrees F or higher
• Pain or redness at your injection site
• Bloody urine or reddish sweat
• Unusual bruises or persistent bleeding
• Persistent cough, sore throat, pneumonia
• Allergic symptoms, such as shortness of breath, swelling of feet or ankles, rash, swollen throat or tongue

Between its red color and potential for serious complications, using Adriamycin may make you take pause. That said, it is very effective in reducing the risk of recurrence in early stage breast cancer, especially tumors that are node positive. Be sure to weigh the pros and cons of this medication with your doctor and give all your treatment decisions careful consideration.