Trimetrexate (Neutrexin) is a drug that was first used to treat bacterial infections, and is now being investigated as a treatment for several different cancers.
Trimetrexate is most commonly used to treat pneumonia in patients with acquired immunodeficiency syndrome (AIDS). However, it was recently discovered that the drug was able to kill a variety of different cancer cells. As a result, trimetrexate is now considered to be an investigational drug for cancer treatment.
Ongoing clinical trials are using trimetrexate to treat a number of cancers including advanced colon and rectal cancers, advanced pancreatic cancer, and advanced squamous cell cancers of the head and neck. Results from many trials are still preliminary, but trimetrexate appears to be most promising as a treatment for advanced colon and rectal cancers.
Trimetrexate glucoronate works by stopping cells from using folic acid (vitamin B9). As a result, cells cannot make essential components they need to survive, and they die. Because trimetrexate is toxic to both cancer cells and healthy cells, it is always used in combination with leucovorin (Wellcovorin, citrovorum factor). Leucovorin is a drug that protects healthy cells from the harmful effects of certain types of chemotherapy .
Trimetrexate can also enhance the anti-cancer effect of another chemotherapy drug called fluorouracil (Adrusil, 5-FU). Fluorouracil is frequently used to treat patients with colon and rectal cancers.
In clinical trials, patients with colon and rectal cancers were given trimetrexate, fluorouracil and leucovorin for 8-week cycles. A cycle consisted of six weeks of treatment followed by two weeks rest with no treatment. Patients received trimetrexate intravenously, with the dose depending on their weight. Twenty-four hours after trimetrexate treatment, patients received intravenous fluorouracil and leucovorin treatment. Some patients also took oral leucovorin every six hours for several days after their intravenous chemotherapy.
Patients with squamous cell cancer of the head and neck received trimetrexate in combination with cisplatin (Platinol), leucovorin and fluorouracil in a 21-day cycle. These patients also received surgery or radiation therapy . Pancreatic cancer patients received 8-week cycles of trimetrexate, fluorouracil and leucovorin, similar to that given to patients with colon cancer .
Patients who are given oral leucovorin as part of their chemotherapy must take their medication. Trimetrexate is a toxic drug, and patients who do not take leucovorin may experience severe side effects. Pregnant women should not take trimetrexate because it may harm the fetus. Women who are taking trimetrexate should avoid becoming pregnant. In addition, women should not breast feed while taking this drug. The liver and kidney are used to break down and eliminate trimetrexate from the body. As a result, patients with a history of liver or kidney disease should tell their doctor.
Patients taking trimetrexate will have their blood monitored regularly to check for the development of myelosuppression . Myelosuppression is a condition where a patient's bone marrow makes fewer blood cells and platelets than normal. As a result of this condition, patients have an increased risk of infection, may bleed more, and may experience symptoms of anemia . Trimetrexate may also cause damage to the kidneys and the liver. Some patients also experience nausea and vomiting , and may develop a rash or inflammation and sores in their mouths. Taking leucovorin with trimetrexate helps to reduce or eliminate the risk of experiencing many of these side effects.
Trimetrexate is known to interact with several other drugs. Some antifungal drugs such as ketoconazole (Nizoral) and fluconazole (Diflucan) interfere with the way the body breaks down trimetrexate. The antibiotic erythromycin also has this effect. Patients taking these drugs will be monitored carefully. The toxic effects of trimetrexate can be increased by other drugs. Patients should therefore tell their doctor about any medication they are taking whether it is prescription or over the counter.
Alison McTavish, M.S.
—A drug used to protect healthy cells from toxic chemotherapy.
—A condition where the bone marrow makes fewer blood cells and platelets than normal.