Gemzar (gemcitabine) is a chemotherapy drug that can be used to treat mesothelioma patients. It is currently approved to treat certain cases of ovarian, pancreatic, non-small cell lung, and breast cancers only, but research shows it may help mesothelioma patients when combined with other drugs.[1]
What Is Gemcitabine?
Gemcitabine is the generic name of the Eli Lilly drug called Gemzar. The U.S. Food and Drug Administration (FDA) approved Gemzar in 1996.[1] It is now available as a generic drug from companies like Teva Pharmaceuticals, Hospira, and Fresenius.
What Cancers Are Treated with Gemcitabine?
FDA-approved uses for gemcitabine include treatment for:[2]
- Relapsed and advanced ovarian cancer (in combination with carboplatin)
- Non-small cell lung cancer (in combination with cisplatin)
- Pancreatic cancer
- Metastatic breast cancer in combination with paclitaxel
Physicians can use medications outside their narrow approval indications (called off-label), and gemcitabine is often used in this manner to treat bile duct cancer and bladder cancer.[2]
Is Gemcitabine Used for Mesothelioma?
The FDA has not approved gemcitabine for mesothelioma except for use in combination with gemcitabine.
The results of the clinical trials are mixed but largely positive. This should lead to further clinical trials and, eventually, new combination therapies to help more mesothelioma patients.[3]
How Effective is Gemzar for Lung Cancer?
Some people exposed to asbestos develop lung cancer rather than mesothelioma. Gemcitabine is approved for non-small cell lung cancer and has been proven effective for many patients.
A phase III trial for lung cancer patients compared treatment with gemcitabine alone and combined with carboplatin. The combination provided a greater benefit to patients. Those receiving both chemotherapy drugs lived longer and had a greater response and longer disease-free progression time.[]
How Does Gemcitabine Work?
Gemcitabine belongs to a class of drugs called antimetabolites.[2] Antimetabolites interfere with the enzymes that make DNA in cells.
They do this by mimicking compounds the enzymes would normally bind to, halting the action of those enzymes. Since DNA is required for cell division, once the cancer cells cannot make DNA, they stop spreading.
How Is Gemcitabine Administered?
Like most chemotherapy drugs, gemcitabine is administered through intravenous infusion. Traveling through the bloodstream, it intervenes in the division of fast-growing cells. While gemcitabine effectively destroys cancer cells, it can also affect some healthy cells in the body.
What Are the Side Effects of Gemcitabine?
Because gemcitabine does not specifically target cancer cells, it can cause uncomfortable, painful, and sometimes serious side effects. The most common side effects are:[2]
- Nausea
- Vomiting
- Anemia
- Hair loss
- Mouth sores
- Loss of appetite
- Reduced white blood cell count
- Excessive protein in the urine
This drug can also cause fever, skin rashes, labored breathing, swelling in the extremities, low blood platelets, and increased liver enzymes.
Some patients are not good candidates for gemcitabine because of its toxic effects. This includes pregnant women because this drug can lead to serious birth defects. Patients with weakened immune systems may also need to avoid gemcitabine.
Suppression of white blood cell production in bone marrow can be severe, making patients susceptible to life-threatening infections. Patients with liver disease may also be more susceptible to liver damage from gemcitabine.[1]
How Are Mesothelioma Patients Treated with Gemcitabine?
Gemcitabine is administered to some mesothelioma patients as a chemotherapy drug. Gemcitabine is not commonly used for mesothelioma, but some patients might benefit.
Most patients with mesothelioma who receive gemcitabine and other chemotherapy drugs do so as part of a multimodal treatment strategy. This might include surgery before or after chemotherapy, radiation therapy, or immunotherapy.
Intravenous Gemcitabine for Mesothelioma
The most common way to deliver chemotherapy drugs like gemcitabine is intravenously. Injected into a vein, the drug circulates in the body and targets fast-growing cells.
There are issues with this type of administration. It is not very specific, which means the drugs target and damage many healthy cells. This leads to many side effects.
Intrathoracic Gemcitabine for Mesothelioma
One of the newest areas of treatment in pleural mesothelioma is HITHOC or hyperthermic intrathoracic chemotherapy. More often used in peritoneal mesothelioma patients, this strategy circulates heated chemotherapy drugs in the area of the tumors rather than being injected intravenously.
The peritoneal version, called HIPEC, has been successful in helping many patients live longer. HITHOC is still in development but could become more common for pleural mesothelioma treatment. It involves circulating heated chemotherapy drugs in the pleural and thoracic space, usually after surgery to remove tumors.
In a recent review of HITHOC, researchers concluded that it can be safe and effective when used with gemcitabine and other chemotherapy drugs.[5]
Gemcitabine and Mesothelioma – Ongoing Research
While the FDA has not approved gemcitabine for mesothelioma, researchers are attempting to determine its role in treating this difficult cancer. Several early studies, including those that have advanced to phase II clinical trials, show potential for gemcitabine combined with other drugs.
These trials have been satisfactory for the National Comprehensive Cancer Network (NCCN) to place gemcitabine in their Guidelines for second-line treatment in mesothelioma.[6]
- A 2002 phase II trial in Australia tested gemcitabine along with cisplatin in pleural mesothelioma patients. One-third of patients saw some reduction in tumor size, while nearly two-thirds experienced stabilization in tumor growth. Only 8% of patients saw no benefit. Most patients in the trial reported a better quality of life after treatment, so gemcitabine improved the cancer symptoms.[7]
- Another phase II clinical trial, published in 2012, used a combination of gemcitabine, cisplatin, and bevacizumab. Bevacizumab is an anti-angiogenesis drug that acts against tumors by reducing their ability to grow new blood vessels. A tumor has difficulty growing without a blood supply. The combination of these three drugs improved overall survival for patients in the study. The medications also improved progression-free survival times, the time between treatment, and the point at which a tumor begins to regrow.[8]
- A study phase II clinical trial reported promising results in 2017. It compared gemcitabine and pemetrexed, both combined with cisplatin. Both treatments provided some of the longest survival times yet seen in similar studies.[9]
- Another study reported in 2020 that combining gemcitabine with the immunotherapy drug ramucirumab significantly improved overall survival times in mesothelioma patients. They received this therapy as a second-line treatment.[10]
- Researchers in China are working on a better delivery method for cancer drugs. In a recent study, they used carbon nanotubes to deliver gemcitabine to tumors in patients with non-small cell lung cancer. The system targets tumors more precisely and protects more healthy tissue from the harmful damage of chemotherapy drugs. This research could have implications for pleural mesothelioma patients in the future.[11]
These and ongoing clinical trials show great promise for gemcitabine as a treatment for mesothelioma; however, more studies are necessary. Researchers will likely continue combining gemcitabine with other chemotherapy drugs.
How Do Mesothelioma Patients Qualify for Gemcitabine?
Although not standard therapy, some mesothelioma patients can benefit from treatment with gemcitabine. Your medical team will select the best medications and treatments for your particular needs.
Talk to Your Doctors About Gemcitabine
If you are interested in trying gemcitabine, talk to your medical team about whether it makes sense for you. They will be able to tell you if gemcitabine could provide benefits or if there are reasons you shouldn’t try it.
Mesothelioma Clinical Trials with Gemcitabine
If your cancer center doesn’t offer it, look at clinical trials. Your doctors can determine if you qualify for any ongoing trials using gemcitabine. There are currently two trials using gemcitabine and recruiting mesothelioma patients who qualify:
- Switch-Maintenance Gemcitabine After First-Line Chemotherapy In Patients With Malignant Pleural Mesothelioma. This trial is testing the use of gemcitabine as a maintenance drug after standard, first-line chemotherapy in patients with pleural mesothelioma.[12]
- Study of IDE397 in Participants With Solid Tumors Harboring MTAP Deletion. In this trial, researchers are combining gemcitabine and other medications with a new drug called IDE397. They need patients with tumors that have not responded to standard treatments. Locations include Arizona, California, Indiana, Maryland, Massachusetts, New York, Oklahoma, Tennessee, and Texas.[13]
They may also combine the drug with new targeted compounds like immunotherapy drugs and vaccine therapies. Testing chemotherapy drugs for unapproved uses often leads to new treatments and additional options for patients struggling with diseases like mesothelioma.
