Doxorubicin

Doxorubicin is a chemotherapy drug used to treat several different types of cancers since the 1970s. It is sold under various brand names and as a generic and is manufactured and distributed by multiple pharmaceutical companies. Doxorubicin is approved by the U.S. Food and Drug Administration (FDA) to treat several types of cancer, but not mesothelioma.

Although not officially approved for any type of mesothelioma, doctors often prescribe doxorubicin for mesothelioma patients, particularly in combination with other drugs and treatments. Clinical trials, some still ongoing, are increasing our understanding of how effective this drug is against mesothelioma. The drug has risks and side effects, some very serious. But when carefully combined with other drugs, in spite of the risks, doxorubicin may prove to be very effective in treating mesothelioma.

What is Doxorubicin?

Doxorubicin is the generic name of a drug used to treat several types of cancer through intravenous injection. It is often used as a chemotherapy combination drug, administered along with others for greater efficacy in slowing or stopping the growth of cancer cells. It is sold as a solution to be injected or as a powder that can be made into the solution. Some brand names of Doxorubicin are Adriamycin, Rubex, and Doxil and it is currently manufactured by Teva Pharmaceuticals, Janssen Pharmaceuticals, Pfizer, Bedford Laboratories, and other companies.

The first FDA approval for doxorubicin came in 1974 and was awarded to Pharmacia and Upjohn. The FDA has since approved changes in dosing, generic forms of the drug made by various pharmaceutical companies, and new uses for which the drug has been proven to be effective and relatively safe.

How it Works

Doxorubicin is an anthracycline, a type of antibiotic. This class of chemotherapeutic agents is made up of drugs derived from Streptomyces bacteria. Although they are antibiotics, they are useful in treating cancers because anthracyclines damage DNA, resulting in cell death. As with many chemotherapy drugs, this cell-killing effect is not limited to cancer cells, so healthy cells in the body can also be destroyed, leading to unpleasant side effects.

Uses for Doxorubicin

FDA approval for doxorubicin includes specific types of cancer that it has proven effective against with some risks. Doctors may prescribe the drug for unapproved or “off label” uses, and they sometimes do so for mesothelioma. FDA approval includes treating ovarian cancer after earlie treatment with a platinum-based drug has failed. Doxorubicin can also be used to treat multiple myeloma in combination with the drug bortezomib, and it is approved to treat Kaposi’s sarcoma related to AIDS, after other chemotherapy combinations have failed. It is not approved for treating any type of mesothelioma, but it is often used for such patients, especially in studies and clinical trials.

Side Effects

Because doxorubicin kills non-cancerous cells too, it can cause some side effects. The most common include fatigue, hair loss, dizziness, eye pain, discolored urine, increased thirst, weight loss and loss of appetite, nausea, vomiting, fever, diarrhea, constipation, skin rash, mouth sores, anemia, and a weakened immune system that can lead to infections. Many of these side effects are common to all chemotherapy drugs.

Doxorubicin may also cause hand and foot syndrome, a skin reaction on the palms of the hands and the soles of the feet, most commonly a few weeks after starting chemotherapy. The symptoms include stinging in the hands or feet, cracked, dry, and peeling skin, thickened skin like a callus, redness, blistering, and swelling. Hand and foot syndrome can be very painful and restricts movement and the use of the hands. Patients who experience it should report it to their doctor and consult with a dermatologist.

Black Box Warning and Serious Risks

Doxorubicin may also cause more severe reactions. The FDA includes a black box warning — its most serious warning — for more severe side effects. The drug may leak into surrounding tissues at the injection site and cause serious damage as well as pain, itching, blisters, and sores.

Doxorubicin may also cause life-threatening heart problems, even years after the conclusion of treatment. This includes congestive heart failure — the risk increases with the dose of the medicine. Patients taking it may also be susceptible to serious infections due to suppression of production of blood cells, including the immune system’s white blood cells, in the bone marrow. Doxorubicin may also damage the liver and make a patient more likely to develop leukemia. Doctors must be careful to monitor patients before, during, and after treatment for these serious problems. Some patients may not be eligible for treatment with doxorubicin because of existing heart, liver, or immune system impairments.

Studies of Doxorubicin to Treat Mesothelioma

Doxorubicin has not been approved by the FDA to treat mesothelioma, but this is largely because there are relatively few patients with this type of cancer. Doctors and researchers have been trying doxorubicin with mesothelioma patients for years and several studies indicate it may be a promising course of treatment.

Some studies are very small, including a case study of just one patient published in 2012. A man with pleural mesothelioma was given a combination of chemotherapy drugs that included a form of doxorubicin called pegylated liposomal doxorubicin hydrochloride. This form is thought to be absorbed more by tumors and less by healthy tissues. The man was given this drug in combination with etoposide and paclitaxel. He responded well and in 2012 was still alive nine years after treatment, a major accomplishment for someone with mesothelioma.

In another study, 67 patients with peritoneal mesothelioma were given doxorubicin along with paclitaxel and cisplatin. The results were astounding, with a median survival time of more than six years. One patient in the study survived 12 years. A smaller study confirmed these results by combining cisplatin with various other chemotherapy drugs. The best results were seen with cisplatin combined with doxorubicin.

Mesothelioma is a difficult cancer to treat, and although it isn’t approved to treat this cancer, doxorubicin is proving to have great potential for these patients. Studies and clinical trials are ongoing and some patients are seeing better results than they could have hoped. The problem is that doxorubicin has the potential to cause some serious side effects like heart damage and infections. For patients with mesothelioma, these risks are often outweighed by the benefits.