Mitoguazone

Definition

Mitoguazone is an investigational (experimental) medicine used to stop growth of cancer and formation of new cancer cells.

Purpose

Mitoguazone may be effective in patients with acute leukemia , chronic myelocytic leukemia , lymphoma , multiple myeloma , head and neck cancers , esophageal cancer , and other types of malignancies.

Description

Mitoguazone, also known as MGBG, was discovered in 1898. The exact mechanism of MGBG action is not fully understood and a variety of mechanisms appear to be involved. Most likely, MGBG's anti-tumor activity comes from inhibition of spermine, a protein necessary for cell reproduction. This drug underwent numerous clinical trials in the early 1960s; however, the trials were discontinued due to severe toxicities noticed when MGBG was given on a daily basis. In these early research trials MGBG was shown to have both anticancer and antiviral activity. Later, researchers discovered that MGBG has a long duration of action in the body and can be given less frequently. In 1976 MGBG enjoyed a rebirth when Southwest Oncology Group started using once weekly administration schedule of this agent in patients with lymphoma (Hodgkin's and non-Hodgkin's type), esophageal cancer, prostate cancer and other tumor types.

In addition to being effective as a single agent, MGBG was used in combination chemotherapy regimens containing ifosfamide , methotrexate and etopo-side (also known as MIME regimen). The best results with MGBG have been obtained against Hodgkin's and non-Hodgkin's lymphoma using MIME regimen.

Mitoguazone appears particularly effective in patients who are malnourished and would be ideally suited for patients with AIDS-associated lymphomas. Another potential advantage of mitoguazone in patients with AIDS is its high penetration into the brain, since the brain is one area frequently involved by lymphoma in this patient population.

Recommended Dosage

Adults

AIDS-ASSOCIATED NON-HODKIN'S LYMPHOMA.

Doses vary between different chemotherapy protocols. One of the schedules used was 600 mg per square meter of body surface area given intravenously on days 1, 8, and then every two weeks.

Children

There is no data available on dosing and use of mitoguazone in children.

Precautions

To maximize treatment effects, patients receiving mitoguazone should observe certain guidelines. In addition to any modifications given by the oncologist, these guidelines should include regular visits with the oncologist and laboratory testing for white blood cell count, liver, and bone marrow function. Avoid any immunizations not approved or prescribed by the oncologist. When necessary wear a protective facemask. Use good oral hygiene to reduce incidence of mouth sores and avoid touching the eye and nasal areas unless hands have been properly washed immediately prior to contact. To reduce bleeding and bruising complications, patients should exercise extreme caution when handling sharp instruments and decline participation in contact sports. Prior to treatment, the patient's medical history should be thoroughly reviewed to avoid complications that might arise from previous conditions such as liver disease, chicken-pox, shingles, peripheral neuropathy (tingling and weakness in hands or feet), suppressed immune system, stomach ulcers, mouth sores, or a history of allergic reactions to various drugs.

Contact a doctor immediately if any of these symptoms develop:

• signs of infection (fever , chills, sore throat)
• pain, numbness, and tingling in fingers or toes
• severe muscle weakness
• nausea and vomiting , and yellowing of the skin or eyes
• unresolved mouth sores
• mental status changes (euphoria, drowsiness, anxiety, emotional instability)
• unusual bleeding or bruising
• skin rash or itching

Side effects

The dose-limiting toxicity of MGBG is muscle weakness. The most common side effect of MGBG is flushing primarily on the face during infusion. Other toxicities associated with MGBG are usually mild, consisting of somnolence, tingling in the face or extremities, ringing in the ears, euphoria, mouth ulcers, nausea, vomiting, and fatigue . This drug also lacks significant myelosuppression , which makes it an ideal agent to consider for combination regimens.

Interactions

The drug and food interactions with MGBG have not been studied in research trials. There is a theoretical drug interaction between MGBG and pentamidine (a drug used to prevent and treat pneumocystis carinii pneumonia in AIDS patients). Pentamidine inhibits the same enzyme in the body as MGBG, which can enhance effects of MGBG. This interaction can either increase effectiveness of MGBG against cancer or put patients at higher risk of its side effects.

Olga Bessmertny, Pharm.D.

KEY TERMS

AIDS

—Also known as acquired immunodeficiency syndrome, caused by the progression of HIV, and is the leading cause of death from HIV. AIDS is characterized by opportunistic diseases, including fungal infections, pneumocystis carinii pneumonia, non-Hodgkin's lymphoma, and other malignant or infectious illnesses.

Non-Hodgkin's lymphoma

—Lymphomas are some of the most treatable cancers with cure rates around 50% in the 1990s. Non-Hodgkin's lymphoma mainly affects people over 50 years of age and has been more difficult to treat than the Hodgkin's type. There has been an increase in non-Hodgkin's lymphoma cases in the last two decades in patients with HIV.