Among the many challenges of managing malignant pleural mesothelioma (MPM) is reliably assessing the response of the disease to our treatment. We don’t want to discard a treatment that is effective, nor do we want to have patients continue on a treatment that isn’t helpful but is causing significant side effects. In oncology, we typically grade our work by comparing an imaging study like a computerized tomography (CT) scan of the chest done after 2-3 cycles of systemic therapy (usually covering a 6-9 week interval) to a baseline scan performed prior to the start of treatment. As you’d suspect, significant tumor shrinkage is good, while growth is bad, and stable disease is somewhere in between. Typically, we want to continue our treatment in the absence of significant progression or prohibitive side effects.

So why is it so difficult to measure response in MPM? Unlike most solid tumors, MPM doesn’t typically appear on scans as a well circumscribed sphere that can be easily measured. Instead, it appears as a rind around the lung, often with irregular contours, sometimes areas of benign plaques from asbestos exposure, and collections of pleural fluid filling the cavity between the outside of the lung and the inner chest wall. Patients who have undergone a palliative pleurodesis, an intervention in which there is deliberate inflammation within the pleural space in order to cause scarring and close off that space (and thereby prevent fluid from filling there), will typically have marked thickening in that area that represents inflammation and scarring (the desired effect of the pleurodesis) that can be remarkably difficult to distinguish from active cancer.

There are various ways to contend with the challenges of measuring response to treatment for MPM. First, metabolic/functional imaging with positron emission tomography (PET) scanning along with fused CT images is often employed, as it can be instructive to see the level of metabolic activity decrease or increase as an indicator of response or progression, respectively, particularly when the thickness of the rind of tissue thought to represent MPM is not obviously increasing or decreasing in thickness. It is worth noting, however, that a pleurodesis is also expected to transiently increase PET activity in the pleural space in the weeks and perhaps even months after this procedure is performed, so it is necessary to be cautious about interpreting changes in PET uptake that have developed following a pleurodesis. Another clue can come from changes in a patient’s symptoms: many patients with MPM will experience chest wall pain from their underlying disease, and changes in a patient’s symptoms are another helpful indicator of the direction that the cancer is moving in when imaging is notoriously ambiguous. Finally, a blood test such as levels of soluble mesothelin-related proteins (MSRP) can potentially serve as a serum-based indicator that the cancer is responding or progressing.

Ideally, we would hope to have a test for assessing treatment response in MPM that is widely available and well validated. We are limited in the relative infrequency of the disease, with patients treated in a wide range of settings with varied levels of expertise in interpreting imaging results that are often ambiguous and complex. In this setting, it is often necessary to accept greater ambiguity, to be pleased to see an absence of convincing progression, and to utilize additional clues such as the trajectory of a patient’s cancer-related symptoms and potentially serum-based testing such as MSRP levels to provide greater direction as we do our best to make good judgments about the value of the treatment being administered.

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It’s easy to get excited about an experimental new cancer drug that delivers tumor shrinkage for 95 percent of the patients who tried it.

It may take many years for a pharmaceutical company to bring a new drug to market, but the financial markets respond quickly to clinical trials that produce those kind of results.

Oncolytics Biotech Inc., a small publicly traded company based in Calgary, Canada, has seen a dramatic surge in value and stock price since releasing results of recent clinical trials involving its lead product Reolysin, which has been especially effective in killing cancer cells.

It could be especially promising for patients with lung cancer and even pleural mesothelioma, the cancer involving the thin membrane surrounding the lungs. Mesothelioma is caused by exposure to asbestos.

Reolysin is based upon a common, and otherwise harmless virus, but it shows powerful and uncommon results when altered and used intravenously in conjunction with chemotherapy.

“Reolysin works freakishly well in combination with typical first-line and second-line chemotherapeutic products,” Oncolytics CEO Brad Thompson told The Canadian Blueprint. “Most good science is found by accident.”

Thompson believes that Reolysin could revolutionize the way many cancers are treated. The latest phase II trial, whose results were released last week, involved squamous cell carcinoma of the lung and the chemotherapy regimen of carboplatin and paclitaxel.

Positive results involving Reolysin and colorectal cancer were presented in January at the ASCO Gastrointestinal Cancers Symposium in San Francisco. In December 2012, the company released results from a phase III study of patients with head and neck cancers. And in October, it completed enrollment in another phase II trial involving pancreatic cancer.

It has shown effectiveness with a broad range of cancers, which could make it particularly valuable. Oncolytics has no drugs on the market yet, but its stock price has more than doubled in the last three months, an indication that big investors believe in the potential of Reolysin.

“Based on these (latest) findings, we intend to continue to look at Reolysin as a treatment for cancers of the lung and cancers that metastasize to the lung,” Thompson said. “It’s exciting to have 95 percent of patients in this study exhibit tumor shrinkage, and these results further suggest that Reolysin may have potential in pre-surgical settings.”

Reolysin is based around the Respiratory Enteric Orphan Virus (reovirus), which is relatively harmless and produces few symptoms. Most people are exposed to it as children. And while the body’s own immune system can stop the Reolysin from replicating in healthy cells, it can be designed to infect and destroy cancer cells with specific mutations.

The latest study included 20 patients, and 19 of them exhibited overall tumor shrinkage. An earlier study showed an overall progression-free survival of 7.4 months. One of the biggest benefits of Reolysin is the lack of side effects, especially compared to other cancer therapies.

The concept of using a virus to help kill cancer cells is not new. Viruses can be engineered to selectively infect and reproduce in tumor cells, effectively killing cancer cells. Viruses are playing a big role in novel gene therapy.

Scientists at the Mayo Clinic in Minnesota, in collaboration with the National Cancer Institute, are studying a genetically altered measles virus to test its effectiveness against pleural mesothelioma.

Oncolytics Biotech has been focusing on the development of viruses as potential treatment options for a broad range of cancers. Reolysin is its lead product.

An award winning reporter and writer, Tim Povtak is a senior content writer for the Mesothelioma Center. He previously worked at the Orlando Sentinel and then at AOL. You can contact him directly tpovtak@asbestos.com with any story ideas or comments. Twitter Facebook Reddit Delicious Stumbleupon

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Deepak Chopra, one of the world’s most acclaimed holistic physicians, once told followers: “Instead of thinking outside the box, get rid of it.”

Several mesothelioma therapies currently under investigation fall outside the box of conventional treatments. Cancer stem cell research, biomarker research and developments in gene therapy are inspiring an ever-increasing range of options beyond surgery, chemotherapy and radiation therapy.

But while those treatments fall outside the box, a new treatment destroys its boundaries.

The therapy? A fowlpox vaccination.

Yes, that fowlpox vaccination – the shot that farmers traditionally give chickens and turkeys to prevent viral outbreaks of contagious lesions.

Recently, researchers have found a way to take the vaccine from the farmyard to the cancer center – and with surprisingly encouraging results.

Pox viruses are considered some of the most ideal agents for targeted cancer treatment. The viruses are considered safe to modify into a vaccine that help the body’s own immune system kill off cancer cells.

The fowlpox virus is especially easy to modify. Lab workers can design it to enter healthy cells and deposit a set of specific proteins that can trigger an immune response.

Once inside the body, the vaccine may also generate additional white blood cells that can continue carrying out the mission.

This concept lies at the heart of a new study, conducted by researchers at the University of Hawaii.

The study, which will appear in a future issue of the International Journal of Cancer, tested a fowlpox vaccination that was adapted to contain the protein known as survivin.

Survivin is “a protein … that makes cancer cells resistant to chemotherapy,” the study’s lead researcher, Pietro Bertino, told Asbestos.com. The protein also regulates programmed cell death, a process known as apoptosis.

“My hypothesis was that, by survivin inhibition, all mechanisms that force the cancer cell to stay alive during chemotherapy could be turned off,” Bertino explained.

After he realized this protein could potentially play a major role in mesothelioma treatment, he had to find a way to get it into the body. An immunotherapy approach turned out to be the key. This is where the fowlpox vaccine comes in handy – it was the perfect vehicle to deliver the survivin to the tumors.

Bertino’s research team injected mice with malignant mesothelioma cells. They then provided a dose of the survivin-laced fowlpox vaccine. Some mice received the vaccine under the skin, while others received it directly into the peritoneum.

Both delivery methods produced a “significant immune response.” This response correlated with delayed tumor growth and improved overall survival. Better yet, none of the mice developed potentially serious side effects – like autoimmune conditions or infertility – after treatment.

Bertino’s team is now considering future directions for the vaccine.

“The fowlpox vaccine is our first attempt to induce an immune response against mesothelioma cells that can be used for both therapeutic and preventive purposes. We recently started collaborating with EpiVax … [and together] we identified a list of very immunogenic survivin peptides that should generate high responses in human subjects.”

When fully developed, this vaccine may have a distinct edge over other therapies.

“Successful immunotherapies have the advantage [of inducing] an immune response … that may persist years after vaccination. Chemotherapy, on the other hand, has an affect limited to a few days,” Bertino explained.

Because chemotherapy offers such a short response, patients have to participate in several cycles of the treatment.

“Repeating chemotherapy cycles usually induces high toxicity,” Bertino adds. The fowlpox vaccine could help patients avoid those serious side effects, which often include severe nausea and hair loss.

Certain vaccines also show more promising results than chemotherapy drugs, which rarely put mesothelioma into remission.

“With immunotherapy, our group induced complete tumor regression in animal models of mesothelioma. We never achieved a similar result in studies with chemotherapy.”

Since it is still in its animal testing phase, the fowlpox vaccine still has a long way to go before it is approved for human use. But Bertino feels that the promising results from his study can justify future clinical trials in due time.

As research teams continue to take the fowlpox vaccine to the next level, other vaccination options are already available through clinical trials.

In 2010, researchers tested a vaccine made from a patient’s own immune cells and tumor antigens. The trial – the first human trial of its kind – found that the vaccine could help “jump-start” the immune system’s response to the tumors.

Early last year, a UK-based research group announced another vaccination trial, this time for the TroVax® shot. Once the study officially begins, the researchers will see if this virus-based vaccine can stimulate the immune system to attack cancerous cells.

Our clinical trial database can help interested patients find a vaccine trial near them. For more updates on the fowlpox vaccine – including notifications when it advances to human studies – be sure to check back for future news posts.

Bertino, P. (4 February 2013.) Pietro Bertino, PhD., email interview with Asbestos.com. Bertino, P., Panigada, M., Soprana, E., Bianchi, V., Bertilaccio, S., Sanvito, F., … & Carbone, M. (2013). Fowlpox-based survivin vaccination for malignant mesothelioma therapy. International Journal of Cancer. Retrieved from http://onlinelibrary.wiley.com/doi/10.1002/ijc.28048/abstract American Thoracic Society. Possible vaccine for mesothelioma proven safe. (4 March 2010). Retrieved from http://www.eurekalert.org/pub_releases/2010-03/ats-pvf030210.php National Institutes of Health: A phase II trial to assess TroVax® plus chemotherapy in patients with malignant pleural mesothelioma (SKOPOS). (30 March 2012). Retrieved from http://clinicaltrials.gov/show/NCT01569919 Faith Franz is a content writer for the Mesothelioma Center. She joined the team in January 2011 to help mesothelioma patients empower themselves through knowledge about their diagnosis. Twitter Facebook Reddit Delicious Stumbleupon

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