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Multimodal Therapy

Multimodal therapy is the combination of two or more types of cancer treatments. Studies have shown using a multimodal treatment approach for mesothelioma can extend survival better than individual therapies.

Multimodal therapy can be a combination of traditional treatments, like surgery and chemotherapy, as well as emerging treatments like immunotherapy. The combination of treatments recommended will depend on the patient’s individual case and characteristics, such as the type of mesothelioma and their overall health. If patients are strong enough to undergo multimodal therapy, the treatments have been shown to extend survival. One study found that 46% of patients with early stage pleural mesothelioma achieved 5-year survival with multimodal therapy, compared to the average 5-year pleural mesothelioma survival rate of 12%.

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How Multimodal Therapy Treats Mesothelioma

Research shows singular modes of treatment for malignant mesothelioma have limited success in improving survival. Without any form of treatment, mesothelioma patients’ survival times range from four months to one year. For optimal patient outcomes, doctors usually recommend multimodal treatment. Multimodal therapy uses one form of treatment as a primary therapy and may include treatment before and after the main therapy to improve outcomes.

  1. Neoadjuvant Therapy: Treatment given prior to the primary therapy to enhance efficacy.

  2. Primary Therapy: This therapy option is believed to be the best treatment. For mesothelioma, this is often surgery.

  3. Adjuvant Therapy: Treatment given after the primary therapy to reduce risk of recurrence.

The order of mesothelioma multimodal therapy will vary based on type and stage of disease, cell type and the general health of the patient. After considering these characteristics, doctors will determine the best order and dose of each treatment. Research shows mesothelioma patients that most benefit from multimodal therapy include those with epithelial cell type, negative resection margins (no presence of cancer cells in the tissues around where the tumor developed) and no metastases within the lymph nodes.

Components of Multimodal Therapy

Multimodal therapy involves the combination of two or more modes of treatment. Most commonly for mesothelioma, this will be a combination of chemotherapy, surgery and radiation administered in various orders. Other more experimental treatments, like immunotherapy or gene therapy, may also be used for either curative or palliative gains.

Common Treatments Included in Mesothelioma Multimodal Therapy
Chemotherapy: When used alone, chemotherapy has limited success in extending survival. When used neoadjuvantly in a multimodal approach, some studies have found patient survival improved to 22 months or longer. Surgery: Depending on the stage and type of mesothelioma, patients may undergo surgery to remove cancerous tissue. When viable, surgery is often the primary therapy in multimodal treatment. Radiation: Radiation therapy can be used to treat mesothelioma at any stage. For multimodal approaches, radiation is often used as an adjuvant treatment, though clinical trials are also testing the efficacy of radiation before surgery.

The order in which the treatments are administered varies by the mesothelioma treatment center and an individual’s case. A patient's stage of disease, cell type and overall health are all factors used to determine the most effective treatment order for their diagnosis.

Although courses of treatment for patients may vary, researchers have found certain treatment combinations that have effectively improved life expectancy. For pleural mesothelioma, one of the most common multimodal approaches entails surgery, including an extrapleural pneumonectomy (EPP) or pleurectomy/decortication (P/D), followed by adjuvant chemotherapy and radiation, or chemoradiation. For many patients, surgery is performed first to remove as much cancerous tissue as possible, followed by a course of chemotherapy four to six weeks later. Radiation may then be administered over the course of several weeks. In some studies, this combination treatment has been found to prolong mesothelioma patient survival time up to 23.9 months, compared to six months to one year without this treatment, and doctors continue to test different combinations of these treatments to improve efficacy.

Though surgery combined with chemotherapy and radiation is considered the standard of care for pleural mesothelioma, researchers have also been testing other combination therapies like intracavitary photodynamic therapy (PDT) and intracavitary chemotherapy. PDT is light-based treatment, which produces oxygen that in turn kills the cancerous tumors. When used after P/D, researchers found that PDT led to a median survival of 58 months for patients with epithelioid mesothelioma. Intracavitary chemotherapy involves chemotherapy delivered directly into the body’s cavity, such as the pleura, instead of intravenously. Administering the chemotherapy in this way enables the use of higher doses. Mesothelioma treated with EPP or P/D followed by intracavitary chemotherapy has a median overall survival of 35 months.

Immunotherapy has also been a focus of many mesothelioma clinical trials, applied as singular treatments or in multimodal plans. Currently, researchers are considering the promise of combining immunotherapy and chemotherapy to treat pleural mesothelioma. One recent clinical trial testing immunotherapy drug Ad.IFN with chemotherapy found an overall response rate of 25%, with an 88% disease control rate, meaning patients didn’t experience metastasis or spreading of the cancer. More than 60% of the patients in the trial achieved stable disease after treatment.

For patients with peritoneal mesothelioma, the preferred multimodal treatment also includes surgery, when viable. Cytoreductive surgery, which focuses on removing all cancerous tissues and impacted organs, followed by a heated chemotherapy wash called hyperthermic intraperitoneal chemotherapy, or HIPEC, has been found most successful in treating the cancer. HIPEC involves warming the chemotherapy drugs and circulating them throughout the patient's abdomen to kill any remaining cancer cells. Surgery and HIPEC is the standard of care for peritoneal mesothelioma when diagnosed in the early stages of disease.

According to results from one recent study, patients with malignant peritoneal mesothelioma treated in this way achieved a median overall survival of 53 months. Of the 401 patients analyzed, more than 80% had 1-year survival and 47% experienced 5-year survival. Other clinical trials have found similar success, with one noting patients surviving 92 months or longer. Without this treatment combination, patients typically live six months to one year following diagnosis.

Success Rate of Multimodal Therapies

Success following multimodal therapy can vary based on order of treatment, dosage and the individual patient. However, studies have shown multimodal treatment can reduce recurrence and extend survival for some patients.

The ability to reduce recurrence rates among mesothelioma patients undergoing multimodal therapy has increased the appeal of the particular treatment type, since cancer recurrence is common with all forms of mesothelioma. Researchers have found that certain multimodal treatments may help reduce recurrence rates. One study found that intensity-modulated radiation therapy (IMRT) as an adjuvant therapy following an extrapleural pneumonectomy decreased local recurrence rates. The study found only 14% of patients that received IMRT had local recurrence, compared to 42% that received the typical form of radiation.

For patients who are not candidates for radiation, adjuvant chemotherapy is another promising treatment option to improve recurrence rate and overall survival. A retrospective study found that on average, mesothelioma patients that underwent surgery alone experienced recurrence 10 months after their treatment. The patients that had surgery followed by chemotherapy did not experience recurrence for an average of 37 months.

Additionally, the researchers concluded that adjuvant systemic chemotherapy results in improved patient survival when compared to surgery alone. The 51 patients who received both surgery and chemotherapy achieved a mean survival of 35 months. The 13 patients treated with surgery alone had an average survival of 13 months.

While there have been promising results following various multimodality treatments, researchers are continuing to test new combinations, doses and orders to improve patient recurrence and survival rates.

Multimodal Treatment Eligibility

Mesothelioma multimodal therapy is a very aggressive treatment plan that may not be suitable for all patients. Additionally, newer treatment options included in multimodal therapy, like immunotherapy, are currently only available in clinical trials, meaning patients interested in receiving these treatments would have to be eligible for the various trials.

To undergo the common trimodal therapy (chemotherapy, surgery and radiation), patients must be strong enough to heal properly following surgery, endure the toxicity of chemotherapy and be able to safely receive radiation treatments. Patients who may have had radiation treatments in the past may have reached the limit that the body can safely tolerate, making the treatment option no longer viable. Mesothelioma patients undergoing multimodality treatment may experience side effects associated with each of the treatment options utilized for their case.

Side Effects of Common Mesothelioma Treatments
Chemotherapy
  • Anemia
  • Mouth sores
  • Nausea
  • Vomiting
Surgery
  • Blood clots
  • Changes in heart rhythm
  • Wound infections
Radiation
  • Inflammation of the esophagus
  • Inflammation of the lungs

When a patient's care team is combining treatments, they must consider how the treatments interact and impact one another. Doctors consider side effects that may result following each treatment and how that may impact the efficacy of the following therapies, but also how the therapies may eliminate future treatment options. For example, pleural mesothelioma patients that undergo P/D cannot receive adjuvant radiotherapy because of the risks associated with radiation and the lungs. These potential trade-offs must be considered by a patient’s care team when determining the best treatment options for an individual’s case.

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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