Melphalan: An Overview

Summary

• ‍BRAND: Alkeran^®‍
• DRUG TYPE: Anti-cancer chemotherapy drug‍
• CONDITIONS TREATED: Different types of cancer including myeloma and ovarian cancer‍
• ADMINISTRATION: Injectable liquid or white tablet

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Definition

What is Melphalan?

Melphalan is a chemotherapeutic drug used to treat certain types of cancer such as multiple myeloma and ovarian cancer. Melphalan belongs to a class of drugs known as alkylating agents.¹ These drugs bind to nucleic acids, disrupt activity along 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). Chemotherapeutic drugs that affect cells only when they are dividing are called cell-cycle specific; however, alkylating agents such as mechlorethamine are most effective during the resting phase and are cell cycle non-specific.²

A particularly dangerous characteristic of cancer cells is their inability to respond to contact inhibition, a mechanism whereby normal cells stop dividing when they contact another cell similar to themselves. Overriding this limit on cell division deregulates growth control and allows cancer cells to multiply more often and rapidly. However, this rapid division is one of the reasons why cancer cells are more easily destroyed by drugs which interfere with cell division like melphalan. Unfortunately, chemotherapeutic drugs do not discriminate between normal and cancerous cells, and normal cells that divide frequently, such as blood cells and cells lining the gastrointestinal tract or hair follicles, can be adversely affected as well.²

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Use & Administration

What is melphalan used for:²

• Multiple myeloma
• Ovarian cancer
• Neuroblastoma
• Rhabdomyosarcoma
• Breast cancer
• Some condition protocols prior to bone marrow transplant

How is melphalan given:²

• You may administer this medication to your pet using an oral tablet or your veterinarian may choose to administer a liquid solution into your pet’s vein (intravenous).
• If taken as a pill by mouth, tablets come in a 2 mg size and the dose will be determined by your veterinarian.
• Give this medication to your dog 1 hour before to 2 hours after meals since stomach should be relatively empty.
• The amount of Melphalan that your dog will receive depends on many factors, including height and weight, general health or other health problems, and the type of cancer or condition being treated. For example, Melphalan is often used in combination with other drugs such as prednisolone (a steroid) or a targeted drug such as bortezomib (a proteasome inhibitor).³ Your veterinarian will determine your dog’s dose, schedule, and mode of delivery.

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Precautions

Before using melphalan

Tell your veterinarian if your pet is allergic to melphalan, ingredients mixed with melphalan, 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 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: Cyclophosphamide (Cytoxan), chlorambucil, and ifosfamide
• Ethylenimines:  Thiotepa and hexamethylmelamine.
• Alkylsulfonates:  Busulfan (Myleran, Busulfex)
• Hydrazines and triazines: Altretamine, procarbazine (Mutalane), dacarbazine and temozolomide (Temodar).
• Nitrosureas:  Carmustine (BiCNU), melphalan (CeeNu), and streptozocin.
• Metal salts:  Carboplatin, Cisplatin, and Oxaliplatin

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

Before and during your dog’s treatment your veterinarian will order blood tests to check blood cell counts, metabolite 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:⁴

• Received radiation therapy or other chemotherapy within the last 4 weeks
• Has kidney or liver disease
• Is pregnant or breast-feeding
• Has recently been vaccinated or is scheduled for a vaccination

While using melphalan

Keep a diary of any unusual reactions your dog may have to the medication. Your doctor may need to delay your pet’s treatment or adjust the dose of melphalan depending on your pet’s response and any side effects that your dog experiences. Do not stop administering the drug without discussing it with your veterinarian.⁴

• Give your dog Melphalan at around the same time every day
• Follow the directions on the prescription label carefully, and ask your vet or pharmacist to explain any part you do not understand.
• Do not give your pet more or less of the drug or administer more often than prescribed by your vet.
• The length of treatment depends on the types of drugs your pet is taking, how well their body responds, and the type of cancer.

Side effects and overdose

Possible side effects

It is important to remember the following caveats:²

• Most animals do not experience all of the side effects listed.
• Side effects are often predictable in terms of their onset and duration.
• Side effects are almost always reversible and will go away after treatment is complete.
• There are many options to help minimize or prevent side effects.
• There is no relationship between the presence or severity of side effects and the effectiveness of the medication.
• Side effects of melphalan and their severity depend on how much of the drug is given; high doses may produce more severe side effects.
• Side effects also depend on the combination of other drugs being administered and/or concurrent radiotherapy.
• Side effects from melphalan most often develop in the gastrointestinal tract with more serious side effects arising from bone marrow suppression.
• Melphalan may reduce blood cell production in bone marrow which reduces your pet’s capacity to fight infection and interferes with the blood clotting mechanism.

The following symptoms require medical attention but are not emergency situations. Contact your veterinarian within 24 hours of noticing any of the following:⁴

• Nausea or vomiting
• Fatigue
• Hair loss
• Loss of appetite and weight
• Sores in mouth and throat
• Weakness, shortness of breath
• Excessive bleeding or bruising

Contact your veterinarian immediately if your pet experiences any of the following:

• Symptoms of an allergic reaction⁴
• Shortness of breath or difficulty breathing
• Chest pain
• Rash, hives, flushing or itching skin
• Drop in blood pressure, fainting

Symptoms of overdose include the following:⁵

• Fever, chills, sore throat, ongoing cough and congestion, or other signs of an infection
• Unusual bleeding or bruising
• Bloody or black, tarry stools
• Dark colored urine
• Bloody vomit
• Vomited material that looks like coffee grounds
• Fast, irregular or pounding heartbeat

Melphalan has also been associated with secondary cancers; however, these are usually associated with repeated treatments or high doses.⁶ Check for lumps or masses.

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Interactions

Consult with your veterinarian regarding any drugs or supplements your pet may be taking prior to treatment with melphalan.

Some products that may interact with this drug include:¹

• Nalidixic acid
• Azathioprine
• Cyclophosphamide
• Amphotericin B
• Chloramphenicol

Serious interactions may occur when taking Melphalan with the following drugs:¹

• Immunosuppressive or immunomodulatory drugs
• Selected multiple sclerosis agents
• Selected myelosuppressive agents such as Clozapine or Deferiprone

Severe interactions can arise when melphalan is combined with the following drugs:¹

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

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Care Tips At Home

• Try to have your dog drink at least two quarts fluid every 24 hours, unless you are instructed otherwise.
• Your dog may be at risk of infection so report fever or any other signs of infection to your veterinarian immediately.
• Wash their feet often, especially if they are prone to licking.
• To help prevent mouth sores, try to rinse your dog’s mouth with 1/2 to 1 teaspoon of baking soda or 1/2 to 1 teaspoon of salt mixed with 8 ounces of water three times a day.
• Avoid activities that could cause injury to your dog.
• To reduce nausea, ask your veterinarian about anti-nausea medications.
• Try and feed your dog small, frequent meals rather than less frequent large meals.
• Avoid dog food with high fat content and allow your dog to have plenty of rest.