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Cisplatin and Mesothelioma

Cisplatin

Cisplatin is a platinum-based chemotherapy drug used to treat mesothelioma and several other types of cancer, either as a single agent or as part of a combination therapy. The chemo drug received FDA approval in 1978 as a treatment for testicular cancer and advanced ovarian and bladder cancers. Though it is not FDA approved specifically for malignant mesothelioma, it is a common treatment option for patients who are able to undergo surgery. Cisplatin was sold by Bristol-Myers Squibb under the name Platinol or Platinol-AQ, but these names may also be used when referencing generic versions of the chemotherapy drug.

How Cisplatin Is Used to Treat Mesothelioma

Cisplatin is typically combined with another chemotherapy drug like Alimta (also known as pemetrexed) to slow or potentially stop cancer growth in patients with mesothelioma. As a result, the chemotherapy combination of Alimta and cisplatin has proven effective for treating mesothelioma and is often given as an initial, or first-line, treatment. Cisplatin may also sometimes be combined with other chemotherapy drugs like gemcitabine.

When cisplatin is combined with Alimta, the chemotherapy drug is given through an IV every three weeks and typically takes a couple of hours to complete. Patients will often undergo several cycles of chemotherapy, though it depends on how well they respond to the drugs and how the cancer reacts to the treatment.

Cisplatin treatments work in the body by interfering with a cancer cell’s DNA, making it unable to reproduce and causing the cell to die. This process, known as apoptosis, is what allows cisplatin to slow or stop cancer cell growth. Unfortunately, because cisplatin is a systemic treatment injected into a person’s veins and can’t distinguish normal cells from cancer cells, normal cells are often damaged in the process. However, they are usually able to repair themselves while the cancer cells are killed.

Possible Side Effects of Cisplatin

Cisplatin, like any chemotherapy drug, may cause side effects, which can vary from patient to patient depending on their reaction to the treatment. Some of the most common side effects experienced by mesothelioma patients are nausea, vomiting, fatigue, temporary hair loss and pain around the injection site. Other side effects associated with cisplatin include kidney toxicity, since the kidneys flush out the chemotherapy, as well as low white and red blood cell counts and hearing loss. Some patients may face additional side effects that are not as common, but still require immediate attention from a doctor.

Less Common Cisplatin Side Effects
  • Difficulty breathing or chest pain
  • Infections
  • Muscle cramps
  • Peripheral neuropathy (tingling in the extremities)
  • Trouble walking
  • Unusual bleeding and bruising
  • Vision problems

Cisplatin has also been associated with kidney damage and renal toxicity, though these concerns can sometimes be addressed with additional hydration before therapy and with diuretics. When combined with Alimta as part of a combination therapy treatment, other side effects may include mouth sores, sore throat, low platelet counts or allergic reactions.

In most cases, side effects will improve once the chemotherapy regimen is complete. Medications may be prescribed by the oncologist to help control some of the more easily treatable side effects like nausea and diarrhea. Patients will also likely undergo hearing tests, blood tests and physicals prior to beginning chemotherapy and will continue to be monitored for possible side effects throughout treatment.

Studies Associated with Cisplatin

In mesothelioma patients, cisplatin is often combined with other cancer drugs to increase efficacy and is the standard of care when combined with pemetrexed. According to one study, the combination of cisplatin and pemetrexed extended average survival to 12.1 months, compared to 9.3 months when treated with cisplatin alone. Recent studies and clinical trials have continued to show the benefits of combination therapies when treating the rare disease, including after radical surgeries like an extrapleural pneumonectomy (EPP) or pleurectomy/decortication (P/D). There are ongoing clinical trials testing cisplatin with other chemotherapy drugs and treatments to improve efficacy and generate better patient outcomes.

Recently, a phase 1 clinical trial studied 104 pleural mesothelioma patients who underwent EPP or P/D surgeries, and then received a combination of cisplatin and gemcitabine as a heated intraoperative chemotherapy (HIOC). The study was performed to determine what dosages were considered safe for patients.

Researchers found that patients with epithelioid mesothelioma who underwent an EPP could extend survival to 25.6 months with combination cisplatin and gemcitabine therapy, compared to 17.1 months average survival with cisplatin alone. Patients undergoing the same chemotherapy treatments after a P/D saw similar results, with those who received the combination treatment surviving 41.6 months on average, more than twice as long as those who were given cisplatin alone. With further study, researchers hope to continue to improve the efficacy of this treatment.

Another ongoing phase 2 clinical trial is testing the efficacy of treating mesothelioma cancer patients with chemotherapy drugs cisplatin and pemetrexed combined with nivolumab, an immunotherapy drug. Other immunotherapy drugs, like bevacizumab, have been previously tested with the combination and shown some success in extending survival. The researchers note the presence of a platinum-based drug, like cisplatin, has been shown to enhance the efficacy of immunotherapy drugs, like nivolumab. As the study progresses, researchers hope to see better results with this new combination as compared to bevacizumab, which showed an average survival of about three months longer than with cisplatin and pemetrexed alone, and provide a new treatment combination for mesothelioma patients.

Author: Linda Molinari

Editor in Chief, Mesothelioma Cancer Alliance

Linda Molinari

Reviewer: Annette Charlevois

Patient Support Coordinator

Annette Charlevois
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Sources

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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

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Fujimoto N, Aoe K, et al. A Phase II Trial of First-Line Combination Chemotherapy With Cisplatin, Pemetrexed, and Nivolumab for Unresectable Malignant Pleural Mesothelioma: A Study Protocol. Clinical Lung Cancer. September 2018; 19(5):705-707. doi: 10.1016/j.cllc.2018.05.001

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OncoLink. Cisplatin (Platinol®). Updated October 2017.

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