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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Patient Advocate Karen Selby explains multimodal cancer treatment for mesothelioma patients.

Clinical studies have shown that multimodal therapy can improve a mesothelioma patient's survival and quality of life by combining various treatments that remove or shrink tumors and control symptoms.

Although each individual treatment option can have a positive impact on patients, clinical studies have proven the best results can only be achieved with a multimodal approach.

Patients with advanced pleural mesothelioma treated with a combination of surgery, chemotherapy and photodynamic therapy had a median survival of three years, according to a 2016 study published in the Annals of Thoracic Surgery. Nineteen of the 73 patients in the study lived more than seven years.

Survival is typically 12 to 18 months for patients treated with chemotherapy alone.

In a 2017 study, relapsed pleural mesothelioma patients who underwent multimodal treatment, which included extrapleural pneumonectomy (EPP) surgery, responded well to additional rounds of chemotherapy.

The type of multimodality used depends on several factors, including the type and stage of the cancer and the health of the patient. For example, many peritoneal mesothelioma patients have successfully undergone a multimodal treatment of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC), while the benefits of heated chemotherapy for pleural patients are less clear.

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Multimodal Treatment Strategies

When developing a multimodal treatment strategy, a team of doctors will evaluate your case individually. They decide on a plan that is most appropriate for you, carefully weighing the risks and benefits of each potential treatment.

Depending on your unique situation, your doctors will choose from several treatments that together offer the most hopeful outlook.

If you respond poorly — or especially well — to any one treatment, they can adjust the treatment plan moving forward. They may add a more promising treatment option, replace an ineffective one or select a new dose for chemotherapy.

Choosing the Right Treatments

Mesothelioma specialists need to consider several important factors when designing a treatment plan, including:

  • The patient's age and overall health
  • Potential surgery risks and toxicity of chemotherapy drugs and radiation therapy
  • The location, stage and cancer cell type
  • Method of approaching cases where cancer has spread to the lymph nodes and other organs

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Choosing the Best Order of Treatment

In addition to selecting the most promising treatments, doctors must also decide on the best order to give them. Any treatment option can be the primary therapy, an adjuvant or a neoadjuvant therapy.

  1. Neoadjuvant Therapy: Given before primary therapy to improve results. In certain cases, doctors perform chemotherapy before surgery. This can improve survival by reducing the size of tumors and increasing the chances of complete removal after surgery.

  2. Primary Therapy: This is the most hopeful and effective treatment option, and it's usually surgery. For pleural mesothelioma patients, this can mean extrapleural pneumonectomy (EPP) or pleurectomy/decortication (P/D). Peritoneal mesothelioma patients can benefit from cytoreductive surgery.

  3. Adjuvant Therapy: Given after primary therapy to help symptoms and prevent cancer from returning. It is also increasingly common for doctors to offer chemotherapy immediately after surgery. Adjuvant chemotherapy aims to kill any microscopic cancer cells left behind after surgery, which researchers blame for the cancer's high rate of recurrence.

The Standard Treatment Approach

Dr. Fontaine goes over multimodal treatment, an aggressive treatment strategy

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

But not all patients are healthy enough for all three treatments. Additionally, all three might not be necessary in certain cases. Doctors rarely use radiation therapy to treat peritoneal mesothelioma.

The advanced size and spread of tumors in the later stages of mesothelioma often disqualifies patients for aggressive surgery. In these cases, doctors may offer chemotherapy as a primary therapy or recommend a clinical trial that explores a new type of treatment.

For early-stage patients, doctors can administer intrapleural neoadjuvant chemotherapy directly into the cancer-ridden pleural space. With traditional chemotherapy, on the other hand, drugs travel throughout the entire body. Intrapleural chemotherapy minimizes the toxicity of the drugs and may allow patients to better tolerate surgery.

Fast 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. David J. Sugarbaker, M.D. pioneered trimodal therapy using extrapleural pneumonectomy (EPP), chemotherapy and radiation therapy while at Brigham & Women's Hospital.

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 (PDT).

For now, most of these treatments are only available to patients participating in a clinical trial.

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 May 2017, the U.S. Food and Drug Administration (FDA) approved pembrolizumab as a first-line treatment for metastatic non-small cell lung cancer, a move that suggests the drug could become a viable treatment option for pleural mesothelioma in the future.

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.

Chemotherapy Prolongs Life Expectancy

According to a 2016 study from researchers at Wayne State University School of Medicine, mesothelioma patients who receive chemotherapy and surgery live longer than patients who receive surgery alone.

Patients who received some form of chemotherapy lived three times longer, on average, compared to patients who did not receive chemotherapy. Those receiving chemotherapy and surgery had a median survival of 16 months, while only 17 percent of patients who didn't chose chemotherapy survived at least one year after diagnosis.

HIPEC Benefits Peritoneal Mesothelioma Patients

Studies show that multiple rounds of HIPEC after cytoreductive surgery can significantly benefit peritoneal mesothelioma patients.

Patients who returned for a second HIPEC procedure survived nearly three times longer than those who underwent only one procedure, according to a 2013 study published in the Annals of Surgical Oncology.

Cytoreductive surgery and HIPEC have become the go-to multimodal approaches for peritoneal mesothelioma. The process involves removing as much of the mesothelioma cancer cells as possible from the abdominal area and then delivering a heated, chemotherapy-based solution directly to the abdomen with the intent of killing remaining cancer cells.

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Matt Mauney is an award-winning journalist with nearly a decade of professional writing experience. He joined 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, Matt was a reporter at the Orlando Sentinel.

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