Rheumatrex (methotrexate) suppresses the immune system and is often used to treat autoimmune disorders. It shows promise as a chemotherapeutic agent for mesothelioma. More research is needed to determine how effective methotrexate may be for mesothelioma treatment and if it is safe to put patients at risk for more infections.
What Is Methotrexate?
Methotrexate is a drug with dual functions. It suppresses the immune system and treats autoimmune disorders like rheumatoid arthritis, in which the immune system mistakenly attacks the joints.
Methotrexate is also a chemotherapeutic drug and can slow the growth of cancer cells and tumors.
First approved by the FDA in 1953, methotrexate has been tested and used for many indications. 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.
While it may not be approved for additional uses, doctors may sometimes prescribe methotrexate for other autoimmune disorders like Crohn’s disease, multiple sclerosis, and other cancers.
It has been tested in patients with mesothelioma and has so far been proven effective. Still, more research is needed to ensure it’s a good treatment for this cancer.
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 antifolate action interrupts a reaction or chemical pathway in a cell and disrupts normal growth there. Methotrexate prevents DNA from being made in cancer cells, which stops cells from dividing and creating new cells, slowing the growth of a tumor.
Methotrexate Side Effects
The most common side effects reported by patients treated with methotrexate are:
- Ulcerative stomatitis
- Reduced white blood cell count
- Abdominal upset
- Fatigue and malaise
- Increased risk of infection
These symptoms are not serious or life-threatening, but other potential side effects can be more serious health concerns for patients:
- Liver toxicity
- Increased liver enzymes
- Liver failure
- Low blood pressure
- Pericarditis or pericardial effusion
- Gastrointestinal ulcers
- Blurred vision
- Speech impairment
- Mood changes
- Severe infections
- Kidney damage, or failure
- Skin damage
- Stress fractures
- Respiratory fibrosis
- Respiratory failure
- 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 medication. The black box warning says methotrexate should only be used to treat severe conditions, like cancer, and those not responding to other drugs.
Methotrexate may suppress white blood cell production in the bone marrow. Suppressing these immune system cells could lead to serious and life-threatening infections. Patients must be monitored carefully 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 could make these worse. Methotrexate can also increase the chance that someone will develop lymphoma.
Despite the risks, methotrexate can help some patients. The risks may be acceptable for patients with life-threatening diseases and difficult to treat, like mesothelioma. Clinical trials and case studies that include mesothelioma patients show methotrexate may be a useful treatment.
Mesothelioma and Rheumatoid Arthritis
One man with rheumatoid arthritis was also diagnosed with mesothelioma. The patient decided against traditional chemotherapy after his surgery but remained on oral methotrexate (similar to the first-line treatment medication pemetrexed). The patient’s cancer didn’t worsen for many years, leading his medical team to believe that perhaps the methotrexate was helpful.
Methotrexate and Vinblastine
In a study with seventeen mesothelioma patients, methotrexate and vinblastine were given, with some patients also receiving cisplatin or carboplatin. These patients were not candidates for surgery, so chemotherapy was their only option.
Nine of the patients responded well to the treatment, and two achieved complete remission. The average survival time was fourteen months; results were better than those seen with standard treatments.
Methotrexate and Gemcitabine
In another study, twenty-one patients with mesothelioma received methotrexate in combination with gemcitabine. Nearly 40% of the patients showed a partial response to the treatment, while nearly half experienced stable disease, meaning the tumor did not grow any larger. Only three patients failed to respond to the treatment.
The median survival time for these patients was nineteen months, much longer than is typical for similar patients. The researchers suggest that the combination of gemcitabine and methotrexate should be considered an effective treatment and potentially as an alternative to using a platinum-based drug to which some patients respond poorly.
A recent clinical trial, which is still recruiting patients, is testing a novel therapy for pleural mesothelioma. Transarterial chemoperfusion involves injecting the chemotherapy drugs directly into the artery that feeds pleural tissue. The combination includes methotrexate with cisplatin and gemcitabine. The therapy shows promise in improving quality of life for patients.
Methotrexate comes with some serious and concerning possible side effects; however, many patients respond well to the treatment, and doctors can often manage side effects through careful monitoring. For patients with mesothelioma, treatment options are limited, so even with the possible side effects and all the risks, trying methotrexate with a combination of other drugs could be a reasonable option. These small studies have shown that it could extend patients’ lives, but more studies should continue with larger groups to determine how serious the risks really are.Get Your FREE Mesothelioma Packet
Page Medically Reviewed and Edited by Kyle J. Becker, PharmD, MBA, BCOP
Kyle J. Becker, PharmD is certified by the Board of Pharmacy Specialties in Oncology Pharmacy. Dr. Becker earned his pharmacy degree from Shenandoah University and he currently serves as an oncology pharmacist at Parkview Cancer Institute.