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Gemcitabine (Gemzar) and Mesothelioma


Gemcitabine, known commercially by its brand name Gemzar, is a drug developed by Eli Lilly and Company that may be used to treat malignant mesothelioma. It has been FDA approved to treat several types of cancer, including breast cancer, ovarian cancer, pancreatic cancer and non-small cell lung cancer (NSCLC). For those diagnosed with mesothelioma who are unable to receive pemetrexed, gemcitabine can be used as a first-line treatment when combined with cisplatin or carboplatin. It may also be used by itself as a second-line mesothelioma treatment for patients who didn’t respond well to initial chemotherapy.

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How Gemcitabine Is Used to Treat Mesothelioma

Gemcitabine helps kill mesothelioma cells by interfering with the DNA and RNA the cancer cells use to replicate themselves. Because of this interference, they are unable to reproduce and eventually go through a death process called apoptosis.

Patients are given gemcitabine through an IV. For patients undergoing first-line treatment using gemcitabine and cisplatin, cycles generally last 3 – 4 weeks, with both drugs given on the first day. In most cases, gemcitabine is given two more times during the cycle, but a doctor can determine whether or not the dosage needs to change based on the patient’s overall health and how the mesothelioma reacts to the chemo drugs.

Similar to other chemotherapy drugs applied intravenously, gemcitabine is unable to distinguish healthy cells from the cancerous mesothelioma cells. This results in healthy cells getting damaged, leading to possible side effects in patients. These cells are usually healthy enough to repair themselves once the treatment is over, and those side effects will often dissipate.

Possible Side Effects of Gemcitabine

Like all other chemotherapy drugs, gemcitabine presents with a variety of side effects that vary depending on the patient, the stage of the disease, dosing and many other factors. Common side effects associated with gemcitabine include fever, nausea, fatigue, loss of appetite, lowering of blood counts and skin rashes. Other side effects may be more serious and should be brought up to the patient’s oncologist or healthcare team immediately.

A mesothelioma doctor will perform blood tests throughout the treatment process to monitor platelet counts, along with white and red blood cell counts. This is because gemcitabine, like many cancer drugs, will impact bone marrow cell production. If the body has too few white blood cells, it makes it easier for infections to develop. Platelets help the blood clot, and when counts are too low it may result in increased bleeding or bruising. Mesothelioma patients are encouraged to avoid over-the-counter medications like ibuprofen or aspirin because they can unintentionally increase their risk of bleeding.

Gemcitabine can have an adverse effect on fetuses, so women should avoid becoming pregnant during treatment, and men should continue to employ proper birth control methods. The chemo drug may also be found in breast milk, so women should avoid breastfeeding while taking gemcitabine.

A doctor can determine what medications may react with a mesothelioma patient’s chemotherapy drugs to prevent adverse drug interactions and other health problems from developing.

Studies Associated with Gemcitabine

When used in combination with cisplatin as part of a heated intraoperative chemotherapy (HIOC), gemcitabine proved to be helpful in a phase 1 malignant pleural mesothelioma clinical trial. According to previous studies, mesothelioma patients receiving a combination of gemcitabine and cisplatin saw partial response rates between 16 – 33% and were able to tolerate the toxicity of the treatment. Researchers also noted about 60% of the participants achieved stable disease, meaning there was no additional tumor growth or spreading, and were able to improve their symptoms and pulmonary function. Studies like these are helping lay the groundwork to determine the efficacy of such treatments for mesothelioma patients.

In a phase 2 clinical trial published in 2017, researchers noticed that patients who were treated with a combination of gemcitabine (delivered over six hours) and cisplatin survived nearly as long as those who received the standard of care treatment of cisplatin and pemetrexed. The group receiving gemcitabine/cisplatin had an overall survival of 18.6 months, but had an objective response rate of 50%, meaning the treatment was effective. In comparison, researchers noted patients in the trial treated with the combination of cisplatin and pemetrexed survived 20.6 months, on average. As a result, the combination of cisplatin and gemcitabine given in low doses over a longer time period could serve as a second-line treatment for patients who saw no improvement with the standard of care.

Overall, researchers continue working to determine the best treatment combinations with gemcitabine to improve efficacy as a first- or second-line treatment for mesothelioma patients. Ongoing clinical trials are testing the chemotherapy drug with various forms of immunotherapy, as well as with other chemotherapy drugs like vinorelbine.

Author: Linda Molinari

Editor in Chief, Mesothelioma Cancer Alliance

Linda Molinari

Reviewer: Dr. James Stevenson

Medical Reviewer and Thoracic Medical Oncologist

Dr. James Stevenson

Burt BM, Richards WG, et al. A Phase I Trial of Surgical Resection and Intraoperative Hyperthermic Cisplatin and Gemcitabine for Pleural Mesothelioma. Journal of Thoracic Oncology. September 2018; 13(9):1400-1409. doi: 10.1016/j.jtho.2018.04.032

de Lara PT, Cecconi V, et al. Gemcitabine synergizes with immune checkpoint inhibitors and overcomes resistance in a preclinical model and mesothelioma patients. Clinical Cancer Research. August 2018. doi: 10.1158/1078-0432.CCR-18-1231

Eli Lilly and Company. GEMZAR - gemcitabine hydrochloride injection, powder, lyophilized, for solution. Updated May 2018.

Eli Lilly and Company. Highlights of Prescribing Information. Updated May 2018.

Kindler HL, can Meerbeeck JP. The role of gemcitabine in the treatment of malignant mesothelioma. Seminars in Oncology. February 2002; 29(1):70-76. doi: 10.1053/sonc.2002.30232

Kovac V, Zwitter M, et al. P3.03-030 Cisplatin with Pemetrexed or Gemcitabine in Prolonged Infusion for Inoperable Mesothelioma: A Phase II Randomized Trial. Journal of Thoracic Oncology. January 2017; 12(1):1362-1363. doi: 10.1016/j.jtho.2016.11.1929

National Cancer Institute. Gemcitabine hydrochloride.

National Comprehensive Cancer Network. Malignant Pleural Mesothelioma. 2016.

National Institute of Health U.S. National Library of Medicine. GEMZAR - gemcitabine hydrochloride injection, powder, lyophilized, for solution. Updated May 2018.

Zucali PA. Target therapy: new drugs or new combinations of drugs in malignant pleural mesothelioma. Journal of Thoracic Disease. January 2018; 10(2):311-321. doi: 10.21037%2Fjtd.2017.10.131

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