THE PET PHARMACY By Wendy C. Brooks, DVM, DipABVP Educational Director, VeterinaryPartner.com

(for veterinary information only)

Brand Name: Leukeran®

Available in 2 mg tablets

Background

The treatment of cancer with medication (as opposed to surgery or radiation) is especially helpful when the cancer in question is not localized to one body area. Using medication allows the body's blood vessels to carry the medication to even remote or otherwise inaccessible areas. This form of treatment 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 affect cell activities that go on predominant in cancer cells but not in normal cells. Most chemotherapy agents focus on the rapid cell division that characterizes the spread of cancer cells.

Chlorambucil is what is called an alkylating agent of the nitrogen mustard group. Alkylating agents work by binding DNA strands so that the double helix cannot unzip and replicate. (In other words, cell division is not possible). They also bind other important biochemicals impairing their function and can even break DNA strands. Cancer cells (and other cells that rapidly divide) cannot reproduce. Lymphocytes, whose normal function involves antibody production and other immune activities, are also very sensitive to the effects of alkylating agents, thus making the alkylating agents helpful in treating immune-mediated diseases (i.e., disease where the immune system erroneously attacks the body).

Alkylating agents as a group have had problems with side effects. Because chlorambucil is relatively slow acting, fewer side effects have been an issue with this medication, especially in feline use. The use of chlorambucil has made the treatment of numerous cancers and immune-mediated diseases more successful especially in cats.

How This Medication Is Used

Chemotherapy protocols for the following cancers have included chlorambucil:

• Lymphocytic leukemia
• Multiple myeloma
• Ovarian cancer
• Lymphoma
• Polycythemia rubra vera

Immune mediated conditions where chlorambucil may be especially helpful include:

• The pemphigus diseases
• Eosinophilic granuloma complex
• Inflammatory bowel disease
• Feline infectious peritonitis
• Immune-mediated hemolytic anemia
• Immune-mediated platelet destruction

Chlorambucil is typically given daily or every other day.

Side Effects

The main side effect of concern with chlorambucil is bone marrow suppression. The bone marrow is one's source of all blood cells, both white cells and red cells. When the bone marrow is suppressed, one can develop an anemia (inadequate amount of red blood cells), a drop in white cells (which constitute the bulk of the immune system), or both. This side effect is generally evident at some point during the second week of therapy and blood testing at this time is definitely in order to determine if this side effect is occurring. Once the medication is discontinued, the marrow should recover in another 1 to 2 weeks, though more severe and long lasting suppression has rarely occurred.

Poodles and Kerry Blue terriers may have hair loss problems on chlorambucil but the hair loss humans experience with chemotherapy generally does not occur with dogs and cats.

Overdose of chlorambucil results in bone marrow suppression in all cell lines as well as seizing.

Interactions With Other Drugs

The bone marrow suppression side effect of chlorambucil may be compounded if chlorambucil is used with other medications that also share possible bone marrow suppression as a side effect. Such medications include:

• Chloramphenicol
• Azathioprine
• Colchicine
• Cyclophosphamide

The use of chlorambucil may lead to the need to increase the dose of allopurinol for patients who take it (such as uric acid bladder stones forming in Dalmatians).

Concerns and Cautions

The DNA poisoning effects of this medication precludes its use in pregnant patients; furthermore, pregnant women should not handle this medication, nor the urine or feces of animals taking chlorambucil.

Chlorambucil should not be used in patients with pre-existing bone marrow suppression.

Chlorambucil is suppressive to the immune system and should be used with caution in patients already immune suppressed (such as FIV+ cats) or with chronic infections.

Chlorambucil may cause permanent infertility when given to patients prior to puberty.

It is our policy not to give dosing information over the Internet.

Date Published: 12/2/2002 2:55:00 PM