Brand Name: Adriamycin, Adriblastin®, Adriblastina®, Adriblastine®, Adrim®, Adrimedac®, Biorrub®, Caelyx®, DOXO-cell®, Doxolem®, Doxil®, Doxorbin®, Doxorubin®, Doxotec®, Doxtie®, Farmiblastina®, Fauldoxo®, Flavicina®, Ifadox®, Myocet®, Neoxan®, Ranxas®, Ribodoxo-L®, Rubex®

Available as conventional and lipsomal injectables

Background

Cancer can be treated in a number of ways: surgery to cut it out, radiation to kill it where it cannot be cut, newer immunologic methods, and, the old classic, medication. One of the criteria used to select a treatment method is the degree to which the tumor is localized in one defined place. A tumor that is not localized to one area of the body cannot be simply removed with surgery or killed with a focussed radiation beam but it is still probably very accessible through the blood vessels that feed it. Medications delivered to the tumor via the bloodstream are able to reach all sorts of remote body areas. The use of medication to treat cancer is called chemotherapy.

In order for chemotherapy to be effective, the medications must destroy tumor cells and spare the normal body cells that may be adjacent. This is accomplished by using medications that exploit cell activities that occur predominantly in cancer cells but not in normal cells. Most chemotherapy agents focus on the rapid cell division that characterizes the spread of cancer cells.

Doxorubicin is a type of anti-cancer drug called an anthracycline glycoside. It works by impairing DNA synthesis, a crucial feature of cell division, and thus is able to target rapidly dividing cells. Doxorubicin is a very serious anti-cancer medication with definite potential to do great harm as well as great good. It may be used alone or in combination with other chemotherapy drugs. It is important to understand its pitfalls and know what sort of monitoring goes with its use.

Doxorubicin is most commonly used in the treatment of lymphoma, osteosarcoma, other sarcomas, carcinomas, and melanoma. Doxorubicin has been widely used in the treatment of small animal cancers for a long time.

How this Medication is Used

Doxorubicin is given only as an intravenous injectable. It is given slowly over approximately 10 minutes in an IV drip rather than as a single quick shot. It is very irritating to the skin, so that those who work with it must wear gloves, gowns, and protective goggles or masks.

If the injection does not go intravenously and some doxorubicin leaks into the tissue surrounding the vein, an extreme reaction occurs in the tissue. (This can happen if multiple attempts at catheterizing the vein leave some leakage points in the vein or if the pet chews the catheter part way out during the administration.) The tissue in contact with the doxorubicin will die and rot away, leaving a large, unhealing wound. Because of the DNA-poisoning nature of doxorubicin, this wound may actually expand or may simply not heal. Amputation may be required. If the tissue exposure is treated immediately with specific flushes, cortisones, and wraps, this disaster has a chance of being averted. A well-seated IV line averts this complication and is prioritized when giving doxorubicin.

Acute allergic reactions (causing facial swelling, hives, vomiting, and possibly heart rhythm problems) are common enough that most patients are pretreated with diphenhydramine, a common antihistamine, to block any such reaction.

Side Effects

Because doxorubicin attacks rapidly dividing cells, it is also toxic to normal cells with high division rates: hair follicle cells, bone marrow cells, and intestinal cells. It is also toxic to muscle cells, particularly heart muscle cells.

Doxorubicin is famous for cumulative cardiotoxicity. This means that there is a maximum amount of doxorubicin a patient can take during its lifetime before its heart is poisoned. In the case of cumulative cardiotoxicity, the heart dilates, becomes incapable of effective pumping, and does not respond to therapy. This obviously is a side effect that must be avoided, which means that the total number of doxorubicin treatments is limited no matter what the cancer is doing. The total dose of doxorubicin widely held to be the "ceiling" is 240 mg/M2 (M2 = square meters of body surface area, a more accurate form of dosing than going by weight), but toxicity can be seen at small levels. Many oncologists will ultrasound the patient's heart to assess function prior to delivering a dose of doxorubicin.

Bone marrow toxicities are common with most chemotherapy drugs as this is one of the areas where the body normally has many rapidly dividing cells. Red blood cells, which carry oxygen and remove carbon dioxide, are made here. The white blood cells that make up our immune systems are born here. The platelets that allow our blood to clot also arise here. Usually, it is the white blood cells and platelets that are most vulnerable. Monitoring tests are needed because if a line of cells becomes suppressed, the oncologist may need to postpone a drug dose, modify a dose, or change to another treatment to make up for the missing blood cells.

Upset stomachs, generally short-lived, are not unusual two to five days after doxorubicin use. Nausea is usually controlled with medication.

Patients on doxorubicin will have trouble growing in fur over shaved areas. Whiskers are often lost and do not regrow.

In cats, doxorubicin is also a kidney toxin, and blood test monitoring is needed to make sure kidney function remains acceptable.

Urine will look especially orange for a day or two post-administration. Owners should avoid handling this urine (wear gloves - see below for more details).

Interactions With Other Drugs

Cyclophosphamide, another prominent anticancer drug, has a potential side effect called hemorrhagic cystitis, where the urine becomes bloody. This side effect becomes more likely when cyclophosphamide is used with doxorubicin. Concurrent use of cyclophosphamide may increase the likelihood of doxorubicin-induced cardiotoxicity, as described above.

Medications that may increase the potential for doxorubicin toxicity include:

• Spinosad-containing flea products (Trifexis®, Comfortis®). A different flea product should be selected.
• Ketoconazole (used for yeast and other fungal infections).
• Cyclosporine (used for immune-mediated diseases including allergy).
• Cyclosporine (used in the treatment of immune-mediated diseases).
• Calcium Channel Blockers (used in the treatment of heart disease).
• Other agents of chemotherapy.

Medications that may decrease the effectiveness of doxorubicin include:

• Glucosamine (a nutritional supplement helpful in the treatment of degenerative arthritis).
• Phenobarbital (a medication for seizures that hastens the removal of doxorubicin from the body).

Concerns and Cautions

• Doxorubicin is activated by the patient's liver. A patient with liver disease may not be able to activate this drug and may not respond as well. Dosage adjustments are needed for these patients.
• Boxers, Doberman pinschers, and Great Danes are predisposed genetically to dilative cardiomyopathy. They may be particularly vulnerable to the cardiotoxicity side effect of doxorubicin and must be carefully screened and monitored.
• Doxorubicin absolutely cannot be used safely in pregnancy.

Doxorubicin is removed from the body via a system controlled by what is called the p-glycoprotein. Some dogs have a mutation that impairs this system and inhibits the removal of this drug, and others, from the body and predisposes them to toxicity issues at doses normally not expected to be problematic. The breeds usually involved are collies, Australian shepherds, long-haired whippets, and others. A DNA test for this mutation may be performed from an oral swab. Test kits are available.

Doxorubicin residue is in urine for up to 21 days after a treatment. Any fecal matter, urine, used cat litter, or vomit should be disposed of by someone wearing disposable gloves. The material and the gloves should be sealed in a plastic bag before disposal in the trash. Treated animals should be discouraged from licking human skin.

Doxorubicin is a tough drug that must be respected, properly handled, and used judiciously. It has tremendous potential to do good, but its drawbacks must be understood with its use. It is important to keep a balanced outlook as this medication is very effective in what it is does and can provide many months of excellent life quality to patients who would otherwise have died.