Multimodal Therapy

Multimodal therapy combines more than one method of treatment. Surgery with chemotherapy and radiation therapy is a common treatment approach for mesothelioma and other cancers. Experimental treatments, such as immunotherapy and gene therapy, can also be added to the mix.

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Although each individual treatment option can have a positive impact on patients, mesothelioma specialists achieve the best results by combining various treatments that control, remove and kill cancer cells.

Clinical studies have proven multimodal therapy — the combination of multiple types of treatment — improves survival rates and quality of life for patients healthy enough to qualify for aggressive cancer treatment. Doctors sometimes also call this approach “bimodal therapy,” when two treatments are combined, or “trimodal therapy,” when three treatments are combined.

A multimodal treatment approach usually centers on a major tumor-removing surgery, with chemotherapy and radiation therapy administered before, after or even during the surgery.

  • For peritoneal mesothelioma patients deemed well enough to tolerate it, cytoreductive abdominal surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is established as the most effective treatment approach.

  • For pleural mesothelioma patients, however, there is currently no single treatment plan that is clearly better than all the others. It depends on the patient’s specific circumstances and the judgement of the specialists overseeing their care.

Not all mesothelioma patients are candidates for a multimodal approach, and aggressive cancer treatments always come with risks of toxicity or complications. However, some cancer survivors have lived years beyond their initial prognosis thanks to the coordinated efforts of cancer specialists from different fields.

In a 2014 multicenter analysis of 1,365 pleural mesothelioma patients, multimodal therapy was linked to a higher median survival time.

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Who Is Eligible for Multimodal Treatment?

A patient’s treatment plan depends on several factors, including the stage and type of the cancer and the health of the patient.

The cancer stage refers to how far the mesothelioma has advanced and spread throughout the body. Early-stage cancer is small and localized, making it easy to target in therapy.

Late-stage cancer, however, may already be so widespread that trying to completely remove it would do more harm than good to the patient. For late-stage patients, doctors usually recommend less invasive palliative treatments that focus on easing symptoms.

The cell type of a mesothelioma tumor effects how well it responds to treatment. Epithelioid tumors are easier to remove in surgery and more responsive to chemotherapy, giving patients with this type of mesothelioma a greater chance to benefit from multimodal treatment.

Most important, a patient’s medical history and overall health determines their eligibility for different types of treatment:

  • Surgeons must ensure the patient’s body is strong enough to endure a major surgical procedure and heal afterward.
  • Oncologists must analyze the patient’s body chemistry and overall health to make sure chemotherapy drugs will not cause too much toxicity.
  • Radiologists must check the patient’s medical history to see if they have already reached the limit for how much radiation they can safely receive.

These qualifications, plus the high cost of cancer treatments, put multimodal therapy beyond the reach of many patients.

A 2016 review of 1,625 mesothelioma patients shows only a small proportion received more than one type of treatment.

No surgery Surgery
No chemotherapy 661 237
Chemotherapy 478 249

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Multimodal Treatment Strategies

The treatments used in multimodal therapy fall into three categories, depending on the timing of each treatment relative to the others.

  1. Neoadjuvant Therapy

    This is given in the weeks or months before primary therapy. In certain cases, doctors administer chemotherapy before surgery to reduce the size of tumors and increase the chance of complete removal during surgery.
  2. Primary Therapy

    This is the most potentially effective treatment option. For pleural mesothelioma patients who qualify for surgery, this usually means an extrapleural pneumonectomy (EPP), which removes a lung and surrounding tissues, or a pleurectomy/decortication (P/D), which removes all visible tumor growth but spares the lung. Certain targeted treatments, such as intraoperative chemotherapy or photodynamic therapy, may be administered immediately after tumor removal, before the surgery is finished.
  3. Adjuvant Therapy

    This is given in the weeks or months after primary therapy. It is common for doctors to administer chemotherapy after surgery to kill any microscopic cancer cells remaining in the body. Sometimes doctors also try to prevent local cancer recurrence with radiation therapy, irradiating the area left behind by a removed lung or directing small, precise doses of radiation along surgical incision sites.
Dr. Fontaine goes over multimodal treatment, an aggressive treatment strategy

Choosing the Right Treatments

Doctors are still experimenting to find the most effective combination and timing of therapies for mesothelioma treatment. Most specialists recommend a three-pronged approach that combines primary surgery with adjuvant chemotherapy and radiation therapy.

A 2014 study of 518 patients showed a link between adjuvant therapies and higher survival rates after surgery.

Treatment 1-Year Survival Rate 2-Year Survival Rate 3-Year Survival Rate
Surgery 52% 34% 21%
Surgery and Chemotherapy 56% 29% 17%
Surgery and Radiation 66% 39% 22%
Surgery, Chemotherapy and Radiation 76% 51% 37%

Quick Fact

With surgery alone, it is nearly impossible for doctors to remove all tumors and prevent them from returning later on. To boost results, they may provide chemotherapy or radiation therapy before or after surgery. Dr. David J. Sugarbaker pioneered trimodal therapy using extrapleural pneumonectomy (EPP), chemotherapy and radiation therapy while at Brigham & Women’s Hospital.

When developing a multimodal treatment strategy, a team of doctors evaluates each case individually, weighing the risks and benefits of potential treatments. Depending on the patient’s unique situation, the team chooses a combination of treatments that together offer the most hopeful outlook.

If the patient responds poorly — or especially well — to any one treatment, the team can adjust the treatment plan moving forward. They may add a more promising treatment option, replace an ineffective one or adjust the dosage of an existing one.

Multimodal Therapy Breakthroughs for Mesothelioma

In recent years, mesothelioma specialists have started combining traditional therapies with new and experimental treatments such as immunotherapy, gene therapy and photodynamic therapy. For now, novel treatments such as these are only available to patients participating in a clinical trial.

Photodynamic Therapy Extends Survival for Years

According to a 2017 study published in the Annals of Thoracic Surgery, patients with advanced pleural mesothelioma treated with a combination of surgery, chemotherapy and photodynamic therapy had a median survival of three years, and 19 of the 73 patients in the study lived more than seven years.

The Abramson Cancer Center of the University of Pennsylvania has sponsored an ongoing phase 2 clinical trial of this novel multimodal approach since 2014.

A 2017 study of 73 epithelioid patients linked a multimodal approach with photodynamic therapy to long median survival times.

Keytruda Shows Promising Results

Pembrolizumab, an immunotherapy drug marketed by Merck & Co. under the brand name Keytruda, has shown effectiveness with mesothelioma patients in clinical trials.

More than half of mesothelioma patients in a clinical trial under the Merck Access Program experienced initial tumor reduction after taking pembrolizumab. All patients had previously received chemotherapy.

In 2016, a phase 1 clinical trial began to test pembrolizumab in a multimodal approach as both a neoadjuvant treatment and an adjuvant treatment, in combination with pleurectomy/decortication and standard chemotherapy.

WT1 Vaccine a Possible Second-Line Treatment

A novel DNA vaccine designed to improve chances of inducing anti-tumor immunity could become a second-line treatment for mesothelioma. A second-line treatment is applied after first-line treatments, such as chemotherapy or surgery, stop working.

In 2016, the FDA awarded Fast Track designation to the WT1 cancer vaccine, also known as galinpepimut-S. The immunotherapy agent targets the WT1 protein, which is expressed in high levels in various cancers, including mesothelioma.

Mesothelioma patients in a phase II clinical trial for the WT1 vaccine had a median overall survival of 24.8 months, compared to just 16.6 months for those receiving a placebo. A phase III trial is slated to begin sometime in 2017.

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Matt Mauney

Matt Mauney is an award-winning journalist with nearly a decade of professional writing experience. He joined Asbestos.com in 2016, and he spends much of his time reading, analyzing and reporting on mesothelioma research articles to ensure people in the mesothelioma community know the latest medical advancements. Prior to joining Asbestos.com, Matt was a reporter at the Orlando Sentinel. Matt also edits some of the pages on the website.

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Sources
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