Methotrexate

The drug methotrexate suppresses the immune system and is often used to treat autoimmune disorders, like rheumatoid arthritis. It is sold as a generic and under the brand names Rheumatrex and Trexall. It was first approved by the U.S. Food and Drug Administration (FDA) in 1953 and was originally made by Dava Pharmaceuticals. It is now made by numerous companies and shows promise as a chemotherapeutic agent for mesothelioma.

As a chemotherapy drug, methotrexate can extend the lives of patients with mesothelioma. On the other hand, there are some serious risks from the drug, including the possibility of a life-threatening infection. More research is needed to determine how effective methotrexate may be for mesothelioma treatment and if it is worth the risk.

What is Methotrexate?

Methotrexate is a drug with a dual function. It suppresses the immune system and can be used to treat autoimmune disorders, in which the immune system mistakenly attacks part of the body, such as the joints in rheumatoid arthritis. Methotrexate is also a chemotherapeutic drug and slows the growth of cancer cells and tumors.

First approved by the FDA in 1953, methotrexate has been in use for decades. It is approved to treat rheumatoid arthritis and psoriasis, both immune system disorders. It is also approved for certain cancers, including gestational choriocarcinoma, acute lymphocytic leukemia, meningeal leukemia, breast cancer, head and neck cancers, lung cancer, non-metastatic osteosarcoma, and some types of lymphoma.

Although it is not approved for other uses, doctors may prescribe methotrexate for other autoimmune disorders like Crohn’s disease and multiple sclerosis, and for other cancers. It has been tested in patients with mesothelioma, and while more work needs to be done, it has so far proven effective in improving patient outcomes.

How it Works

Methotrexate is an antimetabolite, which means that it inhibits the action of an enzyme by binding to that enzyme more effectively than the substance that normally binds to it — in this case folic acid. This interrupts a reaction or chemical pathway in a cell and disrupts normal activity there. Methotrexate prevents DNA from being made in cancer cells, which stops cells from dividing to create new cells, therefore slowing the growth of a tumor.

Methotrexate Side Effects

The most common side effects reported by patients being treated with methotrexate are ulcerative stomatitis, reduced white blood cell count, abdominal upset, nausea, fatigue and malaise, fever, chills, dizziness, and decreased infection resistance. These symptoms are not serious or life threatening, but other potential side effects can be more serious health concerns for patients.

Severe or damaging effects include liver toxicity, hepatitis, increased liver enzymes, liver failure, low blood pressure, pericarditis or pericardial effusion, anemia, anorexia, gastrointestinal ulcers, blurred vision, blindness, speech impairment, changes in mood, severe infections, kidney damage or failure, skin damage, stress fractures, respiratory fibrosis, respiratory failure, and chronic interstitial obstructive pulmonary disease. With so many potential side effects, although they are not commonly seen, doctors must carefully weigh the benefits of methotrexate with the many risks.

Black Box Warnings

In addition to its side effects, the FDA has listed several warnings in a black box on the drug packaging, a warning used for the most severe and possibly life threatening side effects of a medication. The black box warning says methotrexate should only be used to treat severe conditions, like cancer, and those that are not responding to other drugs.

Methotrexate may suppress white blood cell production in the bone marrow. Suppressing these immune system cells can lead to serious and life threatening infections. Patients must be carefully monitored for white blood cell count and infections while on methotrexate. Caution should be taken with patients who have liver, kidney or lung damage or disease, as the drug can make these worse. Methotrexate can also increase the chance that someone will develop lymphoma.

Mesothelioma Studies

In spite of the risks, methotrexate can have great benefits for some patients. The risks may be acceptable for patients with diseases that are life threatening and difficult to treat, like mesothelioma. Case studies and studies with multiple mesothelioma patients show methotrexate may be a useful treatment. One man with rheumatoid arthritis was also treated for mesothelioma. He was on methotrexate for the arthritis, and when he lived longer than expected for mesothelioma patients, his doctors attributed it to the methotrexate.

In a study with 17 mesothelioma patients, methotrexate, cisplatin, and one other chemotherapy drug were administered. These patients were not candidates for surgery; chemotherapy was their only option. Nine of the patients responded well to the treatment and two achieved remission. The median survival time was 14 months, results that are better than those seen with standard treatments.

In another study, 21 patients with mesothelioma got methotrexate in combination with gemcitabine. Nearly 40 percent of the patients showed a partial response to the treatment, while nearly half experienced stability in the disease, meaning the tumor did not grow any larger. Only three patients experienced disease progression in spite of the treatment. The median survival time for these patients was 19 months, much longer that what is typical for mesothelioma patients. The researchers suggest that the combination of gemcitabine and methotrexate should be considered an effective treatment and an alternative to using a platinum-based drug to which some patients respond poorly.

Methotrexate comes with some serious and scary potential side effects and complications. However, many patients respond well to it and never experience the worst side effects. They may also be given a chemoprotective drug, leucovorin, which is designed to counteract some of the complications of methotrexate. For patients with mesothelioma, treatments options are limited, so even with the possible side effects and all the risks, trying methotrexate with a combination of other drugs is a reasonable option. These small studies have shown that it can extend patients’ lives, although more work needs to be done with larger groups and to determine how serious the risks really are.