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Written By: Camryn Keeble

Biphasic Mesothelioma Treatment

Biphasic mesothelioma is a cell type of mesothelioma involving the combination of epithelioid cells and sarcomatoid cells. Treatment options for this cell type depend on where the mesothelioma tumors form and which cell type is most prevalent in the tumors. Surgery, chemotherapy, immunotherapy and radiation are common mesothelioma treatments.

Karen Ritter, RN BSN

Medically Reviewed By

Karen Ritter, RN BSN

Registered Nurse

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Important Facts About Biphasic Mesothelioma Treatment

  • Treatment options for biphasic mesothelioma typically include surgery, chemotherapy, immunotherapy, radiation therapy and emerging treatment options, including clinical trials.
  • Surgery is the most aggressive treatment option for biphasic mesothelioma and can be the most effective method to remove cancer from the patient’s body.
  • Multimodal treatment is the most commonly used treatment approach for biphasic mesothelioma. It involves the combination of multiple treatment methods to optimize the effects of each individual treatment.

Biphasic Mesothelioma Treatment Options

Biphasic mesothelioma treatment options can vary for each patient due to the combination of cell types and where the cancer forms. Biphasic mesothelioma is diagnosed and treated based on which cell type, either epithelioid cells or sarcomatoid cells, make up the majority of the tumors. 

Treatment options are also different for each type of mesothelioma, whether pleural mesothelioma (in the lining of the lungs) or peritoneal mesothelioma (in the lining of the abdominal cavity). Patients with a majority of epithelioid cells in their tumors may be eligible for more treatments than patients with a majority of sarcomatoid cells.

Typical mesothelioma treatment options include surgery, chemotherapy, immunotherapy and radiation. Other options include emerging treatments – such as oncolytic virus therapy, gene therapy and CAR T-cell therapy – which are available through clinical trials.

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Biphasic Mesothelioma Surgery

Surgery is often considered the most effective mesothelioma treatment option because surgeons can remove visible mesothelioma tumors and diseased tissue, allowing other treatments to be more effective. However, mesothelioma can spread quickly, which means surgery may not be an option for some patients. If tumors have already spread to the lungs (for pleural mesothelioma) or to other vital organs in the abdomen (for peritoneal mesothelioma), surgery may not be recommended.

Due to the complexity of biphasic mesothelioma, not all patients are eligible for mesothelioma surgery. The cell type that makes up the majority of the patient’s tumors will determine their eligibility. 

Patients with a majority of epithelioid cells are more likely to be eligible for surgery as these cells are typically easier to identify and remove. However, patients with a majority of sarcomatoid cells are not usually candidates for surgery as these cells grow and spread rapidly and are difficult to differentiate from healthy tissues.

Biphasic Pleural Mesothelioma Surgery Options

Biphasic pleural mesothelioma forms in the lining of the lungs called the pleura. There are two surgical options to treat pleural mesothelioma: extrapleural pneumonectomy (EPP) and pleurectomy with decortication (P/D). These procedures remove the pleura, as it is the most effective way to extract as many pleural mesothelioma tumors as possible. 

Extrapleural pneumonectomy is the most aggressive pleural mesothelioma surgery. It involves the complete removal of the lung affected by mesothelioma tumors. Surgeons also remove the pleura, all or part of the diaphragm, and any other diseased tissue in or around the thoracic cavity.

Pleurectomy with decortication is not as aggressive as EPP as it is considered the “lung-sparing” surgery, meaning the affected lung is not removed. However, the surgery does involve the removal of the pleura, part of the diaphragm and any other diseased tissue in or around the thoracic cavity.

Biphasic Peritoneal Mesothelioma Surgery Options

Biphasic peritoneal mesothelioma forms in the lining of the abdomen called the peritoneum. The surgical treatment for peritoneal mesothelioma is cytoreductive surgery with HIPEC (heated intraperitoneal chemotherapy).

Cytoreductive surgery is known as a “debulking” procedure, which means doctors remove all visible tumors and diseased tissue in the abdomen. When resecting peritoneal mesothelioma tumors, surgeons often remove the peritoneum, omentum (a layer of fatty tissue that covers the organs in the abdomen) and spleen. 

After cytoreduction, or “debulking,” is complete, doctors administer HIPEC, which is a heated liquid chemotherapy solution. The chemotherapy solution is delivered directly into the patient’s abdomen to bathe the entire cavity. This targets any remaining mesothelioma cells not removed during debulking. 

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Chemotherapy for Biphasic Mesothelioma 

Chemotherapy is often recommended to treat mesothelioma. It is traditionally administered into the patient’s bloodstream through an IV drip. The chemotherapy drugs target areas of rapid cell growth, such as mesothelioma cancer cells, and cause them to stop replicating and die. 

There are different types of chemotherapy for biphasic mesothelioma, which include systemic (intravenous) chemotherapy and heated intraoperative chemotherapy. Systemic chemotherapy is the standard method of chemotherapy.

Heated intraoperative chemotherapy is performed during surgery and involves delivering the drugs directly to the diseased location instead of traveling through the bloodstream. HIPEC, the chemotherapy method used alongside cytoreductive surgery for peritoneal mesothelioma, is a type of intraoperative chemotherapy.

Biphasic Pleural Mesothelioma Chemotherapy

Chemotherapy is the most common treatment method for biphasic pleural mesothelioma. There are two FDA-approved chemotherapy drugs for systemic (intravenous) administration: cisplatin and pemetrexed. 

Carboplatin is an alternative to cisplatin. Patients with severe side effects or no effective tumor response from cisplatin and pemetrexed are often given carboplatin and pemetrexed instead. Other chemotherapy drugs, such as vinorelbine and gemcitabine, are used in mesothelioma clinical trials. However, they are not approved as standalone treatments by the FDA.

Hyperthermic intrathoracic chemotherapy (HITHOC) is another type of chemotherapy for biphasic pleural mesothelioma. This is an intraoperative chemotherapy, which is administered during EPP or P/D surgery. HITHOC involves the delivery of a heated liquid chemotherapy drug solution directly into the thoracic cavity, where pleural mesothelioma tumors form. 

Biphasic Peritoneal Mesothelioma Chemotherapy

Patients with biphasic peritoneal mesothelioma are often treated with systemic (intravenous) chemotherapy. Chemotherapy can be administered before surgery, after surgery or on its own for patients not eligible for surgery.

Another form of chemotherapy treatment for biphasic peritoneal mesothelioma is known as HIPEC, or heated intraperitoneal chemotherapy. It is a heated chemotherapy solution administered during cytoreductive surgery and is delivered directly into the abdominal cavity.

The chemotherapy drugs will circulate in the abdominal cavity for 1-2 hours as doctors rock the patient back and forth to ensure the solution coats the entire abdomen. The chemotherapy fluid is then drained from the abdomen, and the abdominal cavity is rinsed with a sterile saline solution.

Side Effects of Biphasic Mesothelioma Chemotherapy

There are many potential side effects of mesothelioma chemotherapy. These side effects can vary from mild to serious complications. It is important to be aware of potential side effects and monitor them as they present. 

Some of the most common side effects of chemotherapy for biphasic mesothelioma are: 

  • Nausea
  • Vomiting
  • Fatigue
  • Weight loss
  • Loss of appetite
  • Diarrhea
  • Body aches
  • Low red blood counts (anemia)
  • Low white blood counts
  • Change in taste (metallic)

Some of the more severe side effects of chemotherapy for biphasic mesothelioma are: 

  • Allergic reactions
  • Liver damage (hepatotoxicity)
  • Inflammation of membranes lining the digestive tract (mucositis)
  • Bruising 
  • Mouth sores 
  • Heartburn 
  • Itching or rashes
  • Damage to the heart muscle (cardiotoxicity) 
  • Increased risk of infection 
  • Nosebleeds

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Immunotherapy for Biphasic Mesothelioma

Immunotherapy is a treatment option gaining more support for the treatment of biphasic mesothelioma. Specialists are beginning to favor immunotherapy over chemotherapy due to its ability to activate the immune system to fight cancer naturally – as if it were an infection or virus – and the less severe side effects. The goal of immunotherapy is to boost the immune system’s response to cancer cells and other invaders. 

The FDA-approved immunotherapy drugs include Opdivo, Yervoy, and Keytruda, which have all been approved specifically for pleural mesothelioma immunotherapy. Opdivo and Yervoy are approved as a combination therapy for unresectable pleural mesothelioma (not eligible for surgery) and Keytruda is approved for a specific subset of cases.

Specialists also support the use of immunotherapy for peritoneal mesothelioma due to the success of immunotherapy in pleural mesothelioma and research in clinical trials, but the FDA has not yet approved any immunotherapy drugs for this type of mesothelioma.

The primary immunotherapy drugs used to treat mesothelioma are:  

  • Opdivo, brand name for nivolumab
  • Yervoy, brand name for ipilimumab
  • Keytruda, brand name for pembrolizumab
  • Imfinzi, brand name for durvalumab

These immunotherapy drugs are called immune checkpoint inhibitors. They block proteins in cancer cells from suppressing the immune system.

Immunotherapy drugs attach to mesothelioma cells, which send a signal to the immune system alerting it of an invader. Once the immune system recognizes the presence of cancer, it sends T cells (main soldier cells of the immune system) to target cells with similar antigens (proteins on cancer cells). Immunotherapy drugs now have successfully improved the immune system’s response to the mesothelioma cancer cells, and the immune system can focus on targeting the remaining cancer cells without damaging healthy cells. 

Side Effects of Biphasic Mesothelioma Immunotherapy

A key benefit of receiving immunotherapy as opposed to chemotherapy is the limited risk of experiencing severe side effects. Since immunotherapy boosts the immune system, the effects of the drugs do not negatively impact the body as harshly. 

Patients receiving immunotherapy are not exempt from side effects and may still experience discomfort caused by mesothelioma immunotherapy drugs, such as:

  • Nausea
  • Vomiting 
  • Body aches
  • Fatigue
  • Dizziness
  • Weight loss
  • Loss of appetite 
  • Skin rashes

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Radiation for Biphasic Mesothelioma

Radiation is another biphasic mesothelioma treatment option used to treat pleural mesothelioma. Radiation therapy delivers high-energy radiation beams through the skin and into the diseased area with the goal of damaging tumor cells. The experience is painless for patients and similar to receiving an X-ray.

However, radiation is not a treatment option for peritoneal mesothelioma due to the vital organs in the abdominal cavity, such as the liver and intestines. Radiation beams can damage essential organs, leading to further health issues.

Mesothelioma specialists use a linear accelerator to send the radiation beams into the body. The beams do not immediately kill the cancer cells, but they do damage the cells beyond repair, which causes them to die without replicating.

There are different types of radiation therapy for biphasic mesothelioma:

  • Photon radiation (traditional method)
  • Intensity-modulated radiation therapy
  • Proton radiation
  • Intraoperative radiation therapy (directing radiation beams into the diseased area during surgery)

Side Effects of Biphasic Mesothelioma Radiation Therapy

One of the most concerning side effects of radiation therapy for biphasic pleural mesothelioma is lung tissue scarring, which is a medical condition called pulmonary fibrosis that results in difficulty breathing.

Other side effects of biphasic mesothelioma radiation may include: 

  • Nausea
  • Fatigue
  • Skin irritation (burning, itchiness, dryness or peeling)
  • Coughing
  • Shortness of breath 

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Multimodal Treatment for Biphasic Mesothelioma 

Multimodal therapy is the medical term used to describe combining multiple types of cancer treatments to optimize effects on tumors. Multimodal therapy for biphasic mesothelioma treatment involves a combination of:

  • Surgery
  • Immunotherapy
  • Chemotherapy
  • Radiation therapy
  • Other emerging treatments

Many specialists believe multimodal therapy is the best method for treating mesothelioma as it is often difficult to treat. Combining multiple treatments offers patients improved outcomes.

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Tumor Treating Fields for Biphasic Mesothelioma

Optune Lua (NovoTTG-100F System) is an FDA-approved tumor treating fields device for the treatment of unresectable malignant pleural mesothelioma. This therapy is an option for patients with biphasic pleural mesothelioma but is not yet FDA-approved for peritoneal mesothelioma treatment.

Optune Lua is a wearable device that creates tumor treating fields, or electrical waves, to interfere with the cell division of cancer cells. The device must be worn 23 hours a day as it sends low-intensity electrical waves into the chest cavity to disrupt cancer cell growth. The electrical waves can damage and kill cancer cells, which can shrink tumors and limit the spread of mesothelioma. 

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Palliative Care for Biphasic Mesothelioma

Palliative care for mesothelioma focuses on improving the patient’s quality of life by addressing their physical and emotional needs. The primary methods of improving a mesothelioma patient’s quality of life include minimizing cancer symptoms, pain management, managing treatment side effects, and providing emotional and spiritual support. 

Palliative care often involves “maintenance” chemotherapy, which is the administration of chemotherapy drugs at a lower dose to maintain the stage of cancer, prevent it from spreading, and minimize side effects.

Other examples of palliative care for mesothelioma include:

  • Draining fluid buildup from the pleural or peritoneal cavity
  • Reducing chest or abdominal pressure
  • Supporting the patient’s psychosocial needs 

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Clinical Trials for Patients With Biphasic Mesothelioma 

Clinical trials for mesothelioma offer patients the opportunity to undergo emerging treatment options that may not yet be FDA-approved. Patients with biphasic mesothelioma may be eligible to enroll in clinical trials focusing on surgery, immunotherapy, chemotherapy, radiation, multimodal therapy combinations and more novel therapies such as oncolytic viruses and gene therapies.

There are open clinical trials accepting patients with biphasic mesothelioma. Many clinical trials for mesothelioma welcome patients with all cell types, while others may limit enrollment to just one specific cell type, such as epithelioid mesothelioma.

While biphasic mesothelioma involves a combination of cell types, patients with a majority of epithelioid cells may be eligible to enroll in an epithelioid-focused clinical trial or vice versa. Most clinical trials accept patients with biphasic mesothelioma.

Frequently Asked Questions About Biphasic Mesothelioma Treatment

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What is Biphasic Mesothelioma?

Biphasic mesothelioma is characterized by the combination of epithelioid cells and sarcomatoid cells, which are two cells detected in mesothelioma tumors. To be diagnosed with biphasic mesothelioma, the patient’s mesothelioma tumor must contain at least 10% of both cells. Once it is determined to be biphasic mesothelioma, specialists determine which cell makes up the majority of the tumors to treat the cancer most effectively.

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How Do You Treat Biphasic Mesothelioma?

The main treatment options for biphasic mesothelioma are surgery, immunotherapy, chemotherapy and radiation therapy. However, the treatment plan heavily depends on which cell type is most prevalent in the patient’s tumors. Patients with a majority of sarcomatoid cells are not usually surgical candidates, but patients with a majority of epithelioid cells are typically eligible for surgery because epithelioid cells are easier to identify and remove due to their growth patterns.

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Can Patients With Biphasic Mesothelioma Receive Immunotherapy?

Yes, immunotherapy is an option for patients with biphasic pleural mesothelioma. The FDA has approved three immunotherapy drugs (Opdivo, Yervoy and Keytruda) for pleural mesothelioma treatment. Opdivo and Yervoy are approved as a combination for unresectable pleural mesothelioma (surgery is not an option), while Keytruda is approved for specific cases of pleural mesothelioma.

Sources & Author

  1. Nivolumab Plus Ipilimumab Improves OS in Malignant Pleural Mesothelioma. Cancer Network. Retrieved from: https://www.cancernetwork.com/view/nivolumab-plus-ipilimumab-improves-os-in-malignant-pleural-mesothelioma. Accessed: 08/11/2020.
  2. Preliminary study highlights the potential of immune checkpoint inhibitors in biphasic mesothelioma. Translational Lung Cancer Research. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/32676326/. Accessed: 07/21/2020.
  3. FDA Approves the NovoTTF-100L™ System in Combination with Chemotherapy for the Treatment of Malignant Pleural Mesothelioma. Novocure. Retrieved from: https://www.novocure.com/fda-approves-the-novottf-100ltm-system-in-combination-with-chemotherapy-for-the-treatment-of-malignant-pleural-mesothelioma/. Accessed: 06/12/2020.
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About the Writer, Camryn Keeble

Camryn Keeble is the senior content writer and editor for Mesothelioma Guide. She creates informative content to educate mesothelioma patients and their loved ones on news, treatments and more. She also works diligently to raise awareness of the dangers of asbestos exposure and the effects of mesothelioma.