Also known as CCNU

Brand Name: Ceenu, Lomustinum, Gleostine

Available in 5 mg, 10 mg, 40 mg, and 100 mg capsules, and as injectable

Background

The basic idea behind using drugs against cancer is that drugs can reach areas of the body inaccessible to surgery. One dose of chemotherapy is transported by the bloodstream to any place where the tumor may be lurking. The medications involved are designed to target cancer cells and leave normal body cells unaffected. Cancer cells engage in activities (such as rapid cell division) that normal cells do 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 instruction manual pages unreadable and unturnable. Rapidly dividing cells, such as cancer cells, are most sensitive to its effects.

How this Medication is Used

Lomustine has the 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 histiocytic sarcoma.

Lomustine can be given either orally or by IV, as the chemotherapy protocol dictates, generally once a month. However, more frequent mini-doses (metronomic therapy) is also sometimes used.

Lomustine should be given with food, and you should wear gloves when giving it. Lomustine should be stored at room temperature and protected from light. If a dose is accidentally skipped, check with your veterinarian or oncologist for instructions, as in most cases, this medication is given on a fairly strict schedule.

Side Effects

Bone Marrow Suppression 1-3 Weeks after Administration

Because lomustine targets rapidly dividing cells, the cells of the bone marrow are vulnerable to whether or not there is any cancer. The bone marrow is where blood cells are produced and 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 when the white count drops so as 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 of 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.

Liver Toxicity

 Lomustine is harsh on the patient’s 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 “Alanine Aminotransferase” (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. Alpha-lipoic acid, an antioxidant supplement, is also sometimes used. Liver failure occurs in < 2% of patients, but vigilance is, in part, what keeps this statistic low.

Kidney Damage

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

Upset Stomach

Normal intestinal cells are also rapidly dividing, and most chemotherapy agents targeting rapid cell division generally cause an upset stomach. Approximately 38% of canine patients on lomustine report upset stomachs, mostly vomiting.

Lung Scarring, Stomatitis, Corneal Weakening

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

Any time two drugs with the 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 the 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.

On the day your pet receives lomustine, and for several days following, gloves should be worn while removing all of the pet's body wastes from the environment. The waste and the gloves may be disposed of in the regular trash but should first be enclosed in a plastic bag.