Lomustine

(for veterinary information only)

ALSO KNOWN AS CCNU

BRAND NAME: CEENU, BELUSTINE, CINU, CITOSTA, LOMEBLASTIN,
                               LOCOSTIN, LOCOSTINE, PRAVA

AVAILABLE IN      
10 mg, 40 mg, and 100 mg
TABLETS and         
as INJECTABLE      

BACKGROUND

The basic idea behind drugs of cancer chemotherapy is for them to reach areas of the body inaccessible to surgery and to kill only the cancer cells leaving the normal cells of the body alone. Cancer cells are involved in activities (such as rapid cell division) that normal cells are not and these activities make them vulnerable to certain drugs. Lomustine is a member of the nitrosurea class of chemotherapy agents which acts by binding DNA to other DNA strands or to protein in such a way that the DNA double helix strand cannot replicate. In addition to essentially tangling DNA up, lomustine generates a by-product that prevents normal DNA function. Remember that DNA is the instruction manual for the cell. Continuing the analogy, lomustine makes the pages unreadable and unturnable.

HOW THIS MEDICATION IS USED

Lomustine has the special ability to penetrate the blood/brain barrier which means it can be used to treat cancers of the nervous system.

The usual tumors against which lomustine is most commonly used are: lymphoma (particularly cutaneous (skin) lymphoma), mast cell tumors, brain tumors, kidney tumors, lung tumors, and melanoma.

Lomustine can be given either orally or intravenously, as the chemotherapy protocol dictates, generally once a month.

SIDE EFFECTS

Because lomustine targets rapidly dividing cells, the cells of the bone marrow are vulnerable whether or not there is cancer present. The bone marrow is where blood cells are produced and special attention is generally paid to the white blood cells whose numbers typically drop about a week after the lomustine dose is given. Often antibiotics are given during the week where the white count drops to at least in part make up for the blow to the immune system caused by the drug. Platelets, cells involved in blood clotting, also drop in number with lomustine but generally recover by the time for the next dose. If they have not, the dose may be delayed. Bone marrow effects are more pronounced in cats thus lower doses of lomustine are typically used.

Lomustine is harsh on the patientís liver as well. Liver disease first manifests as a change in lab testing, long (average of 10 weeks) before the patient actually feels ill. In one study, 7 out of 12 dogs with lomustine-related liver disease died and the ones that recovered had experienced fewer lomustine doses. To prevent a patient from developing serious liver disease, an enzyme called ďAlanine AminotransferaseĒ (ALT) is monitored before each lomustine dose. If there is any elevation, the lomustine treatments are discontinued. No information is available regarding liver toxicity in cats on lomustine so currently the canine monitoring protocols are recommended for both species. Sometimes patients are given silymarin to help detoxify the liver or SAMe to assist in liver tissue repair.

Kidney damage from lomustine is not common but is usually included in the monitoring.

Normal intestinal cells are also rapidly dividing and most chemotherapy agents targeting rapid cell division generally cause an upset stomach. Lomustine is not associated with upset stomach which poses a tremendous advantage of this drug over others at least from the patientís perspective.

Other side effects that have been reported include: oral inflammation, scarring of lung tissue, and thinning of the surface of the eye (corneal de-epithelialization).

INTERACTIONS WITH OTHER DRUGS

Lomustine is removed from the body by the liverís detoxification processes within hours of administration. Phenobarbital, the most common oral anti-convulsant in pets, enhances the enzymes involved which means that pets on phenobarbital will remove lomustine from their bodies faster than they normally would and lomustine will not work as well.

Any time two drugs with potential to suppress the bone marrow are used together, the risk of marrow suppression becomes greater. Such drugs would include other agents of chemotherapy, chloramphenicol, possibly methimazole, etc.

Any time two drugs that have potential to suppress immune function are used together, the risk of infection becomes greater. Such drugs would include other agents of chemotherapy and corticosteroids.

CONCERNS AND CAUTIONS

As with all chemotherapy agents, lomustine should not be used in pregnancy, lactation, or in animals to be used for breeding.

Live vaccinations should not be given while the patient is on lomustine.

Page last updated: 6/5/2013