Gemcitabine

The chemotherapeutic drug gemcitabine is most often used to treat pancreatic, ovarian and breast cancers. Doctors also found success in the treatment of pleural and peritoneal mesothelioma and certain types of lung cancer, and often use the drug in combination with another chemotherapy drug to treat these forms of cancer.

Most chemotherapeutic drugs work by killing cells with complex chemical reactions. Gemcitabine can slow the growth of pleural mesothelioma by killing cancer cells and interfering with DNA replication.

Gemcitabine Information

Gemcitabine
  • Other names: Gemzar
  • Manufactured by: Eli Lilly and Company
  • FDA-approved: Yes (to treat ovarian, breast, pancreatic and non-small cell lung cancers)
  • Used or tested in: Pancreatic cancer, breast cancer, ovarian cancer, lung cancer and mesothelioma cancer.

These drugs target cells that are dividing rapidly including cancer cells. Unfortunately, the treatment may also affect some healthy cells, including cells that are involved in hair growth and immunity. This is why many chemotherapy patients lose hair and become easily susceptible to illness.

Gemcitabine was discovered and developed by scientists at the pharmaceutical company Eli Lilly. Gemzar is the registered name of gemcitabine for injection. Mesothelioma patients who do not respond well to platinum-based chemotherapy drugs like cisplatin or carboplatin may do well on gemcitabine instead.

Treatment for Mesothelioma

Gemcitabine chemotherapy is most often performed on an outpatient basis and is administered intravenously. Treatment typically involves a trip to a doctor’s office, clinic or hospital. The procedure usually takes a few hours, with the actual administration of the drug lasting around 30 minutes. In most cases, it is administered once a week for up to seven weeks, though the length of treatment and strength of dosage will depend on the type and stage of cancer.

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The drug may be administered alone or in combination with another chemotherapy drug. It may be used in first-line or second-line chemotherapy regimens for mesothelioma. First-line chemotherapy with gemcitabine is most often given in combination with another chemotherapy drug such as cisplatin. Second-line chemotherapy with this drug may be administered alone or in combination depending on the patient and how they responded to first-line chemotherapy.

Gemcitabine is used more often in second-line chemotherapy for mesothelioma than first-line because cisplatin and pemetrexed produce longer survival rates. However, gemcitabine may be swapped out for cisplatin if a patient doesn’t tolerate cisplatin well.

It is necessary for patients to inform their doctor of current medications being taken, including all prescription drugs and any vitamins, supplements or over-the-counter medications, before beginning gemcitabine treatment. In addition, anyone who has impaired liver or kidney function is generally not advised to use gemcitabine, because the drug can cause severe liver and kidney damage. Because gemcitabine and most chemotherapy drugs are known to be harmful to unborn babies, women who are pregnant or breastfeeding should not use this drug.

Side Effects

Side effects of treatment can include the following:

  • Nausea and vomiting
  • Tendency to bruise or bleed easily
  • Constipation or diarrhea
  • Swelling in the ankles, feet or hands (edema)
  • Less frequent urination
  • Blood in urine, or particularly dark urine
  • Change in kidney function
  • Change in liver function
  • Chest pain
  • Numbness or weakness, most often on one side of the body
  • Confusion, balance impairment, or impaired vision or speech
  • Fever, chills and body aches (similar to symptoms of flu)
  • Sores or white patches inside the mouth
  • Pain or swelling at the location where gemcitabine was administered

People treated with chemotherapy drugs have reduced immune system function because these drugs kill certain immune cells. If you are taking gemcitabine for mesothelioma, it’s important to avoid contact with people who have colds or other infections. A medical face mask may be worn to protect you from contact with germs.

Studies

Several phase II clinical trials have investigated gemcitabine’s effectiveness on mesothelioma. Some phase II trials report higher response rates or higher overall survival rates than other trials report. Despite inconsistency in results, the general consensus is that the drug can benefit people with mesothelioma.

In 2002, an Australian phase II clinical trial evaluated the combination of gemcitabine and cisplatin as first-line chemotherapy for pleural mesothelioma. Researchers reported a partial response (meaning the tumor shrank to some degree) in 33 percent of participants. The tumor was stabilized (meaning no new tumor growth) in 60 percent of participants. Only 8 percent of participants had progressive tumor development while on the treatment. Participants reported improved quality of life following recovery from treatment and improved respiratory function. The overall survival from the start of treatment was 11.2 months.

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In 2012, results were published from a phase II clinical trial led by mesothelioma expert Dr. Hedy Kindler on the combination of gemcitabine, cisplatin and the antiangiogenesis drug bevacizumab. Anti-angiogenesis drugs block the formation of new blood vessels, which is the pathway through which tumors spread cancerous cells in the body. The addition of bevacizumab improved progression-free survival and overall survival in participants with lower pretreatment VEGF levels, but was not significant enough among all participants to warrant further study. However, more recent evidence from a 2016 French phase III clinical trial that combined bevacizumab with cisplatin and pemetrexed reported an overall survival of 18.8 months, indicating that gemcitabine might not be the best chemotherapy drug to combine with bevacizumab.

In 2013, a preclinical study performed in mice found benefit in the combination of gemcitabine, vitamin C and EGCG (epigallocatechin-3-gallate, a naturally occurring chemical in green tea). The combination effectively reduced tumor growth and spreading in mice with peritoneal mesothelioma. The addition of vitamin C and EGCG to a lower dose of gemcitabine produced a survival increase that was identical to survival with a higher dose of gemcitabine. These results indicate that the addition of nutritional compounds may increase the effectiveness of gemcitabine at lower doses, which could diminish side effects.

A 2017 study combined cisplatin with gemcitabine and administered the gemcitabine drug in a low dose for six hours rather than the average dose for 30 minutes. This low-dose approach increases the effectiveness of gemcitabine against mesothelioma, although it did cause more hair loss than the average dose. Overall survival was 18.6 months, which is among the longest survival times reported for mesothelioma chemotherapy.

Studies continue to investigate the best ways to administer gemcitabine for the treatment of mesothelioma. The drug’s effectiveness may be improved with the addition of other chemotherapy drugs, targeted therapies and nutrition. Trials are ongoing to improve the outcomes of people treated with the drug. People facing mesothelioma who undergo treatment with this drug may experience a reduction of symptoms, improved quality of life and extended survival.

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Karen Selby, RN and Patient Advocate at The Mesothelioma Center

Karen Selby joined Asbestos.com in 2009. She is a registered nurse with a background in oncology and thoracic surgery and was the director of a tissue bank before becoming a Patient Advocate at The Mesothelioma Center. Karen has assisted surgeons with thoracic surgeries such as lung resections, lung transplants, pneumonectomies, pleurectomies and wedge resections. She is also a member of the Academy of Oncology Nurse & Patient Navigators.

Sources
  1. ASCO University. (2010). IFCT-GFPC-0701 MAPS trial, a multicenter randomized phase II/III trial of pemetrexed-cisplatin with or without bevacizumab in patients with malignant pleural mesothelioma. Retrieved from http://ascopubs.org/doi/abs/10.1200/jco.2010.28.15_suppl.7020
  2. Eli Lilly. (2013, Nov. 19). Gemzar. Retrieved from http://www.gemzar.com/Pages/index.aspx
  3. Kindler, H.L., Karrison, T.G., Gandara, D.R., Lu, C., Krug, L.M., Stevenson, J.P., … Vokes, E.E. (2012). Multicenter, double-blind, placebo-controlled, randomized phase II trial of gemcitabine/cisplatin plus bevacizumab or placebo in patients with malignant mesothelioma. Journal of Clinical Oncology, 30(20): 2509-2515. doi: 10.1200/JCO.2011.41.5869
  4. Kindler, H.L. & Meerbeeck, J.P. (2002). The role of gemcitabine in the treatment of malignant mesothelioma. Seminars in Oncology, 29(1): 70-76. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/11836671/
  5. Simon, G.R., Verschraegen, C.F., Janne, P.A., Langer, P.A.,Dowlati, A., Gadgeel, S.M., Kindler, H.L. (2008). Pemetrexed plus gemcitabine as first-line chemotherapy for patients with peritoneal mesothelioma: final report of a phase II trial. Journal of Clinical Oncology, 26(21): 3567-3572. doi: 10.1200/JCO.2007.15.2868
  6. Nowak, A.K., Byrne, M.J., Williamson, R., Ryan, G., Segal, A., Fielding, D., & Robinson, B.W.S. (2002). A multicenter phase II study of cisplatin and gemcitabine for malignant mesothelioma. British Journal of Cancer, 87(5): 491-496. doi: 10.1038/sj.bjc.6600505
  7. Volta, V., Ranzato, E., Martinotti, S., Gallo, S., Russo, M.V., Mutti, L., & Burlando, B. (2013). Preclinical demonstration of synergistic active nutrients/drug (AND) combination as a potential treatment for malignant pleural mesothelioma. PLoS One, 8(3): e58051. doi: 10.1371/journal.pone.0058051
  8. Kovac, V., et al. (2017). Cisplatin with Pemetrexed or Gemcitabine in Prolonged Infusion for Inoperable Mesothelioma: A Phase II Randomized Trial. Journal of Thoracic Oncology; 12(1):S1362-S1363. doi: 10.1016/j.jtho.2016.11.1929
  9. Zalcman, G., et al. (2016). Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial. The Lancet; 387(10026):1405-1414. doi: 10.1016/S0140-6736(15)01238-6

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