Chlorambucil: An Overview

Summary

• ‍BRAND: Leukeran^®, Chloraminophene^®, or Linfolysin^®‍
• DRUG TYPE: An anti-cancer chemotherapy drug with antineoplastic and cytotoxic properties‍
• CONDITIONS TREATED: Canine leukemia, lymphoma, multiple myeloma, breast, ovarian and testicular cancer‍
• ADMINISTRATION: Tablet‍
• CYCLES OF TREATMENT: Usually administered every 2 weeks‍
• LENGTH OF TREATMENT: Depends on animal’s condition and response

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Definition

What is Chlorambucil?

Chlorambucil, commonly known as Leukeran^®, is an immune system suppressant and also interferes with the growth and spread of cancer cells in the body. It is often prescribed for pets suffering from immune-mediated disorders or cancers such as leukemia and lymphoma.¹ Since chlorambucil is an alkylating agent, it can form tight bonds with nucleic acids, disrupt DNA strands, and ultimately limit cell division. Normal cells undergo cell division as part of the cell cycle. Basically, the cell goes from the resting phase, through active growing phases, and then divides (mitosis). Alkylating agents such as chlorambucil are most effective during the resting phase and are cell cycle non-specific.²

Chlorambucil can also suppress antibody production and has antineoplastic properties which help to clear the body of abnormal cellular growths in blood and lymphatic systems. This medication is readily absorbed following oral administration and is metabolized by the liver. Most often, it is used in combination with other drugs such as prednisone.³

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Use & Administration

What is chlorambucil used for?

Chlorambucil is an immunosuppressant and anti-cancer medication used to treat canine cancers “off-label”. This latter term is used in veterinary medicine to refer to drugs that have been developed for humans but are modified for use in dogs. Be sure to review your veterinarian’s directions since they may differ from the labeling instructions accompanying the drug which are more applicable to human use. Canine cancers treated with chlorambucil include the following:

• Leukemia
• Lymphoma
• Multiple myeloma
• Breast and ovarian cancer
• Testicular cancer
• Inflammatory bowel syndrome, an immune-mediated disease
• Immune-mediated diseases of skin, joints, and/or kidneys

How is chlorambucil given?

Chlorambucil is either prepared as a compounded liquid or in tablet form. Most often, the tablet is given with food and taken in orally.⁴ It is usually taken once daily, approximately 1 hour before or 2 hours after meals, for 3 to 6 weeks. Sometimes chlorambucil is taken intermittently as a single dose, once every 2 weeks, or as a single dose once a month.^2,5. The length of treatment depends on the types of drugs your pet is taking, the type of cancer being treated, and your pet’s response to the drug.² Your veterinarian may adjust the dose of chlorambucil depending on your pet’s response to treatment and to reduce the potential for adverse effects. The amount of chlorambucil your pet receives and how often it is administered depends on many factors, including height & weight, general health, other health problems, and the type of cancer or condition being treated. Chemotherapeutic drugs that affect cells only when they are dividing are called cell-cycle specific. Since chlorambucil affects cells when they are at rest, it is cell-cycle non-specific and is not typically given in cycles.² Veterinarian will determine your dose and schedule.

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Precautions

Tell your veterinarian if your pet is allergic to chlorambucil, ingredients mixed with the chlorambucil, or reacts to other medications, vitamins or supplements. You can always ask your pharmacist for a list of “other ingredients” included in any medication. This is important since the product may contain inactive ingredients which can cause allergic reactions or other problems.

Also, be sure to mention if your dog is taking other alkylating agents such as:²

• Mustard gas derivatives: Mechlorethamine, cyclophosphamide (Cytoxan), melphalan (Alkeran), and ifosfamide (Iflex).
• Ethylenimines:  Thiotepa and hexamethylmelamine.
• Alkylsulfonates:  Busulfan (Myleran, Busulfex).
• Hydrazines and Triazines: Altretamine, procarbazine (Mutalane), dacarbazine and temozolomide (Temodar).
• Nitrosureas:  Carmustine (BiCNU), Lomustine (CeeNu), and streptozocin.
• Metal salts:  Carboplatin, cisplatin, and oxaliplatin.

If your pet has taken chlorambucil before, but the cancer did not respond to the medication, your veterinarian will probably choose to prescribe a different chemotherapeutic agent.

Before and during your dog’s treatment, your veterinarian will order blood tests to check blood cell counts, metabolites and enzyme levels. This information is used to evaluate immune system function as well as the drug’s effect on the kidney and liver. It is important to let your veterinarian know if your pet has had a history of the following:⁵

• Received radiation therapy or other chemotherapy within the last 4 weeks
• Experienced seizures or a head injury
• Is pregnant or breast-feeding
• Has recently been vaccinated or is scheduled for a vaccination

Chlorambucil must be administered with extreme care, not only for your dog’s health, but for the owner’s safety. Take precautions when handling the medication:⁴

• Be sure to wear gloves and dispose of them after each use.
• Do not allow this medication to come into contact with your skin, eyes, or mouth.
• After delivering the drug and for at least 48 h afterwards, handle your pet’s bodily fluids carefully and wear gloves.
• Seal all bodily wastes and used gloves in a plastic bag before placing them in the trash.
• Do not allow your pet to lick your skin. If this occurs, be sure to wash the area with soap and water.
• If you are pregnant or may become pregnant, please do not handle this medication or breathe dust from the tablets. It passes readily into the bloodstream and has the potential to adversely affect fetus. In addition, this drug passes into breast milk and may harm a nursing infant.⁵

Side effects & overdose

Potential side effects

Although chlorambucil is well tolerated by dogs and side effects almost always disappear after treatment is complete, it is important to observe your pet for any adverse effects. Side effects from chlorambucil most often develop in the gastrointestinal tract with more serious side effects arising from bone marrow suppression. Chlorambucil may reduce blood cell production in bone marrow which reduces your pet’s capacity to fight infection and interferes with the blood clotting mechanism. If you notice any unusual bruising or bleeding, or if your pet becomes listless, shivers, and develops a fever (signs of infection), call your vet immediately.

Chlorambucil is often given in conjunction with other drugs. The most common symptoms include:³

• Vomiting
• Diarrhea
• Loss of appetite
• Fever
• Loss of hair and delayed regrowth
• Abnormal bruising or bleeding
• Tremors or seizures
• Liver and kidney enzyme imbalance
• Breathing problems

More serious side effects include:

• Bone marrow suppression
• Anemia
• Gastro-intestinal tract damage
• Kidney and liver disease
• Lung disease
• Irreversible infertility in males

In case of overdose, contact your veterinarian immediately, particularly if the following symptoms occur:.⁵

• Collapse
• Seizure
• Trouble breathing
• Loss of consciousness

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Interactions

Drug interactions may increase the risk for serious side effects or change the effectiveness of your pet’s medicine. All possible interactions cannot possibly be listed here, so be sure to keep a list of all prescription or non-prescription drugs, herbal products, and any other product that you give your pet. Share this information with your veterinarian.

Chlorambucil may react with the following drugs¹

• Antineoplastic agents
• Bone marrow suppressants
• Corticosteroids
• Immunosuppressive drugs
• Protein-bound drugs
• Amphotericin B

Serious interactions may occur between chlorambucil and the following drugs;⁶

• Immunosuppressive or immunomodulatory drugs
• Selected multiple sclerosis agents
• Selected myelosuppressive agents such as clozapine or deferiprone

Severe interactions can arise when combined with these drugs:⁶

• Alkylating agents such as nalidixic acid
• Selected immunosuppressants such as Talimogene laherparepvec
• Live vaccines
• Immunosuppressive drugs or immunomodulators such as Efalizumab or Natalizumab

Do not start, stop, or change the dosage of any medicines without your vet’s approval.

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Care Tips At Home

If your pet loses their appetite and stops eating, try the following:

• Take your pet’s temperature. Call the hospital if it is above 103^oF or below 99 ^o
• Provide interesting and enticing foods such as chicken, turkey, and hamburger or try chicken and lamb baby food (dogs only).
• Add broth or yogurt to your pet’s food.
• Avoid foods that are too fatty or rich as these can cause digestive problems.
• Call your veterinarian if your pet has not eaten for more than 2 days.

Nausea, Vomiting and Diarrhea

• Call the hospital if your pet experiences any of the following: Temperature is greater than 103^oF or below 99 ^oF; diarrhea lasts for more than 48 h, or vomiting for longer than 24 h.
• Withhold food and water for 12 hours, and then offer small amounts of water every 2 hours.
• If your pet does not vomit after drinking small amounts of water, bland food such as chicken or turkey can be offered (boiled or baked, not fried). Boiled hamburger (fat skimmed off) or boiled white rice are also good choices.
• If your pet tolerates small amounts of these bland meals without vomiting, a normal diet can be resumed gradually over a 3-day period.
• If your vet agrees, give anti-nausea medications as prescribed. For example, 1/2 of a 160 mg tablet of maropitant citrate (Cerenia^®) by mouth once daily (80mg/day) or as required if nausea, vomiting and loss of appetite are noted.
• If diarrhea is persistent, give 1½ tablets (375 mg) of metronidazole (250mg: Flagyl, anti-diarrheal antibiotic) by mouth twice daily for up to 5 days.
• Fortiflora (Anti-diarrheal probiotic) can also be administered to suppress diarrhea. Follow packet instructions for up to 7days.

Hair loss

• Most dogs do not lose their hair following chemotherapy. However, breeds that exhibit continuous hair growth, such as poodles, Bichon Frises and some terriers are more prone to this side effect.
• For those pets that lose excessive hair, perhaps a dog sweater or coat may keep your dog more comfortable when going out in cold weather.

Skin damage

• Occasionally sores develop. If so, try to keep your pet from licking at the area.
• You may need to wrap the limb or apply an Elizabethan (cone) collar to help prevent your pet from licking at the area.
• Call your vet to discuss management if the sores worsen.