Gemcitabine

Quick Summary

Gemcitabine, sold under the name brand Gemzar, is a chemotherapy drug used to treat mesothelioma and other forms of cancer, such as non-small cell lung cancer and soft-tissue sarcoma.

What is Gemcitabine?

For many mesothelioma patients, the most effective chemotherapy combination is cisplatin and pemetrexed. As a result, gemcitabine is typically only used when patients can’t tolerate cisplatin, have an allergy, or there’s another reason the cisplatin and pemetrexed combination shouldn’t be used. When used as part of the first-line of treatment, gemcitabine is often combined with other chemotherapy drugs, including pemetrexed and cisplatin.

Studies have proven that gemcitabine in combination with other chemotherapy drugs has a significantly better outcome than gemcitabine on its own.

Gemcitabine was first discovered by Larry Hertel, who was working for the Lilly Research Laboratory of Eli Lilly and Company in Indianapolis. Dr. Hertel was trying to develop a new antiviral agent and was testing against live leukemia cells when he witnessed the future drug’s ability to inhibit both RNA and DNA viruses. Recognizing the significance of this discovery, Dr. Hertel recorded the agent’s antitumor activity and published his findings in 1990.

Six years later, in 1996, gemcitabine was approved for the treatment of lung cancer, including mesothelioma, as the first line of chemotherapy. The standard treatment at the time was a combination of gemcitabine and cisplatin. However, gemcitabine has since become a second line treatment, combined with pemetrexed, and used for mesothelioma patients who don’t tolerate cisplatin well.

How is Gemcitabine Administered?

Gemcitabine is given to patients intravenously, which is a method that administers the medication directly into the bloodstream. Patients receiving gemcitabine will have an IV tube placed into their arm or wrist, which is connected to a bag that drips medicine into the tube.

In some cases, a central line may be required instead. Central lines are used when traditional IVs aren’t possible due to limited access to a suitable vein. With a central line, a tube is placed into a larger vein of the chest and arm. This tube is typically left in the patient for the duration of the treatment, which can be several weeks or months.

Gemcitabine’s treatment cycle is typically 21 days, with patients receiving the medication once every three weeks. Patients will often receive gemcitabine for several cycles in a row, especially when they demonstrative positive changes.

How Does Gemcitabine Treat Mesothelioma?

Gemcitabine falls into a category of chemotherapy drugs called “antimetabolites,” which prevent cancer cells from dividing. Antimetabolites get absorbed into cells during specific cycles of cell growth and then disrupt those cells’ ability to create the new DNA and RNA that is essential for cell division.

Mesothelioma and other cancers are dangerous to the body because they mutate cells and override their natural death cycles. This causes the cells to overgrow and often clump together into tumors. When cells can no longer multiply, they are forced into a death process called “apoptosis.” Because antimetabolites like gemcitabine disrupt cancer cells’ ability to divide, they trigger this apoptosis and force mesothelioma cells to die off.

Like all chemotherapy drugs, gemcitabine can’t differentiate between cancer cells and healthy cells. Instead, it will attack any cell within the cell cycle it’s been developed to attack. As a result, white cells, red cells, and platelets are often destroyed during the treatment. These healthy cells can replenish themselves after a few weeks, and the hope is that the cancer cells become extinct in the meantime.

Gemcitabine Drug Combinations

Gemcitabine is most effective when combined with other chemotherapy drugs, and is often prescribed by oncologists because of its lower toxicity and milder side effects compared to other chemo medications.

For example, gemcitabine is often chosen as a second-line of chemotherapy for patients who don’t tolerate platinum-based drugs like cisplatin and carboplatin. In this case, gemcitabine and pemetrexed, also called Alimta, is a common combination for mesothelioma patients.

Gemcitabine is sometimes combined with cisplatin or carboplatin, although this combination isn’t quite as common. Gemcitabine and cisplatin can result in high toxicity levels and cause harsh side effects, while gemcitabine and carboplatin toxicity levels are still higher than gemcitabine and pemetrexed. As a result, gemcitabine and either platinum-based chemotherapy is typically reserved for patients who can tolerate high toxicity but aren’t good candidates for pemetrexed.

Cancer researchers continue to research gemcitabine combinations in laboratory and clinical trials. Some of these tests focus on improved chemotherapy combinations, while others are reviewing gemcitabine in combination with smart drugs.

Current Gemcitabine Clinical Trials

Early studies of gemcitabine revealed that the drug has minimal impact on mesothelioma when given as the only chemotherapy treatment. However, gemcitabine is still appreciated by patients and oncologists because of its relatively low toxicity levels. Today, clinical trials for mesothelioma are usually evaluating gemcitabine’s effectiveness when combined with other chemotherapy drugs or therapies.

In a current Phase III study, gemcitabine and vinorelbine are being directly compared to a new experimental drug called pembrolizumab. As a smart drug, pembrolizumab is potent and blocks the interaction between molecules that cause cancer tumors to grow. The hope is that pembrolizumab will stop growth, force tumors into regression and ultimately cause the body to reject the cancer.

Another current clinical trial, in Phase II, is testing transarterial chemoperfusion (killing the blood supply to mesothelioma cells) with gemcitabine, cisplatin, and methotrexate. The study is considering four outcome measures: overall survival, progression-free survival, occurrence of treatment-related toxicity, and quality of life. All four outcomes will be measured for up to 3 years.

Mesothelioma specialists from across the world are also in the process of creating a database of patients who have received gemcitabine or other chemotherapy medications during Hyperthermic Intraperitoneal Chemotherapy, commonly referred to as HIPEC or heated chemotherapy. The international initiative is gathering data and outcomes from 1000 mesothelioma patients and will be able to help determine whether gemcitabine should be used in the HIPEC procedure moving forward. Thirteen countries are participating in the collaborative project, including Australia, Denmark, Germany, and Russia.

Gemcitabine Side Effects

Patients receiving gemcitabine can expect to have some side effects.

While patients aren’t likely to experience every common side effect, they typically do have at least one or two.

  • Fever
  • Headache
  • Muscle pain
  • Chills
  • Fatigue
  • Mild nausea
  • Vomiting
  • Loss of appetite
  • Skin rash

Other gemcitabine side effects may occur. An increase in liver function levels and protein or blood in patients’ urine are also common side effects.

Most gemcitabine patients will have low blood counts, with red cells, white cells, and platelet levels temporarily dipping. During this time, mesothelioma patients are at a greater risk of anemia, infection, or bleeding. These blood levels typically reach their lowest point 10 to 14 days after gemcitabine is received and patients’ blood levels return to normal 21 days after treatment.

Some patients receiving gemcitabine will also have less common side effects. Difficulty sleeping, breathing challenges, hair loss, diarrhea, weakness, and sores in the mouth are reported side effects in 10-29% of people who have had gemcitabine.

Fortunately, all gemcitabine side effects follow predictable patterns and don’t tend to last long after chemotherapy has stopped. Mesothelioma patients can expect the negative side effects of gemcitabine to subside after their treatment ends.

If you’ve been diagnosed with mesothelioma, you may be a candidate for chemotherapy treatment. Talk to one of Patient Advocates today for more information on undergoing personalized mesothelioma treatments.

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Sources
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  2. Chemocare. “Gemcitabine.” Retrieved from http://chemocare.com/chemotherapy/drug-info/gemcitabine.aspx. Accessed on January 25, 2018.
  3. National Cancer Institute. “FDA Approval for Gemcitabine Hydrochloride.” Retrieved from https://www.cancer.gov/about-cancer/treatment/drugs/fda-gemcitabine-hydrochloride. Accessed on January 25, 2018.
  4. U.S. National Library of Medicine. “PembROlizuMab Immunotherapy Versus Standard Chemotherapy for Advanced prE-treated Malignant Pleural Mesothelioma (PROMISE-meso).” Retrieved from https://clinicaltrials.gov/ct2/show/NCT02991482. Accessed on January 25, 2018.
  5. U.S. National Library of Medicine. “Transarterial Chemoperfusion: Cisplatin, Methotrexate, Gemcitabine for Unresectable Pleural Mesothelioma.” Retrieved from https://clinicaltrials.gov/ct2/show/NCT02611037. Accessed on January 25, 2018.
  6. U.S. National Library of Medicine. “International Registry of Patients Treated With Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) (PIPACRegis).” Retrieved from https://clinicaltrials.gov/ct2/show/NCT03210298. Accessed on January 25, 2018.

Last modified: May 7, 2018