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

Treating 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 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 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.

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. Alkylating agents also bind other important biochemicals, impairing their function and even breaking 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 sensitive to the effects of alkylating agents, thus making the alkylating agents helpful in treating non-cancerous 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 cats. 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
• Immune-mediated hemolytic anemia
• Immune-mediated platelet destruction

Chlorambucil is typically given daily, every other day, or every third 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 and red. Since the precursors of these cells are rapidly dividing, they are targeted by chlorambucil. When the bone marrow is suppressed, one can develop an inadequate amount of red blood cells (anemia), 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 seizures.

Interactions with other Drugs

Chlorambucil’s bone marrow suppression side effect may be compounded if it is used with other medications that also have suppression as a possible 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 stone forming Dalmatians).

Concerns and Cautions

The DNA poisoning effects of this medication precludes its use in pregnant patients; further, pregnant women should not handle this medication, or the urine/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-positive 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
Date Reviewed/Revised: 12/13/2009