The Mesothelioma Applied Research Foundation (MARF) is the nonprofit collaboration of patients and families, physcians, advocates, and researchers dedicated to eradicating the life-ending and viscious effects of mesothelioma.

What follows are scientific highlights of the 2008 Conference:

Robert Taub, MD, PhD, Columbia University

Intracavitary Chemotherapy for Malignant Mesothelioma

Dr. Taub has been at the forefront of developing better treatments for both peritoneal and pleural mesothelioma.  Dr. Taub’s team has treated over 120 patients for the past ten years using a protocol that includes surgery debulking (laparotomy, omentectomy, and cytoreduction), insertion of a catheter for 12 infusions of chemotherapy, followed by a second laparotomy and further hyperthermic intraperitoneal chemotherapy, finished with abdominal radiotherapy.  The median overall survival was 70 months. 

See the full report.

 Dr. Taub further noted that multimodal treatment (surgery plus chemo plus radiation) “is necessary to eradicate mesothelioma or lead to a quality prolongation of patient survival.”  He also suggested that two operations to reduce tumor may be more effective than one initial surgery.During the Q&A panel following Dr. Taub’s discussion, he was asked about the possible progression of epithelial cells into sarcomatoid cells.  He responded that it is not common for cells to change from one type to another, but what is necessary is the need for large tissue samples during biopsy to determine the extent of cell types.

 

James Pingpank, Jr., MD, National Cancer Institute

Analysis of Survival in 101 Patients with Malignant Peritoneal Mesothelioma Undergoing Systematic Surgical Cytoreduction, Continuous Hyperthermic Peritoneal Perfusion (CHPP) and Early Post-Operative Intraperitoneal Chemotherapy

Similar to Dr. Taub’s presentation, Dr. Pingpank shared results from a recent study where patients underwent surgical resection followed by heated chemotherapy at 42-43 degrees Celsius pumped through the body for 90 minutes.  Overall survival of patients was approximately 40 months.

The NCI learned that mesothelioma can be controlled through treatment of regional therapy.  However, patients should be identified for high risk early disease recurrence in order to determine chemotherapy’s role as treatment.

Raja Flores, MD, Memorial Sloan-Kettering Cancer Center

Surgical Options for Treatment of Malignant Pleural Mesothelioma

Dr. Flores discussed the wide range of treatment options from the highly radical extra pleural pneumonectomy (EPP) which removes the affected lung to observation alone.  He also clarified the way data is compiled in research studies so that patients may better understand this information when making decisions about treatment.

Initially, Dr. Flores discussed the different ways that research studies track survival, beginning either at the time of diagnosis or when symptoms began (which might have been years before a firm diagnosis is made).  He cautioned individuals to find out which of these methods a research program with long survivals is using.  Furthermore, a problem with older studies is the lack of a CAT scan and no staging system.  In older research studies, late stage patients were grouped with early stage.  Often, because CAT scans were not used, tracking of disease progression was inadequate.  Dr. Flores explained the need to further stratify mesothelioma cases by their proper pathology, separating the epithelial type (which has better responses to treatment) from sarcomatoid type (which is more aggressive). 

Dr. Flores added that any doctor who does not refer a patient to see a specializing surgeon is clearly not familiar with the results that surgeons obtain.  The medical community still has a misconceptionabout the mortality related to radical surgery which is no longer the case.  Again, the poor survival rates were linked to patients at all stages and cell types lumped together. Mortality rates were once at 31% for EPPdecades ago but are currently less than 5% now, another reason to reevaluate the need for surgical management.

After explaining how to better understand research results, Dr. Flores explained the way he determines which surgery a patient should undergo.  Though a PET/CT scan is the best tool to determine the activity in the chest, this test is often inaccurate.  Therefore, a surgeon does not always know what is involved until the surgery begins.

For tumors that have formed in the fissures of the lung, which is advanced, Dr. Flores performs the EPP surgery, a procedure which usually involves an “en-bloc resection of the lung, pleura, pericardium, and diaphragm.”  However, if the tumor has not progressed that far, he performs the pleurectomy with decortication (P/D) which “involves resection of the parietal and visceral pleurae, pericardium and diaphragm when necessary while sparing the lung.”  Both surgeries aim to remove gross disease or in other words, provide a complete response (as opposed to chemotherapy which cannot achieve such a response).

Dr. Flores said that in a recent study, 31 patients survived 51 months.  Furthermore, Dr. Flores reported on the recent success of the P/D.  In a new clinical trial, patients at Sloan-Kettering may undergo neoadjuvant therapy followed by the P/D or the EPP (a new choice where the EPP was previously the only option). 

Robert Kratzke, MD, University of Minnesota Medical School

Post-Operative Intrapleural Chemotherapy for Mesothelioma

Dr. Kratzke believes that though trimodal therapy for mesothelioma (which usually includes some combination of chemotherapy, surgery, and radiation) may offer the best survival rates, there are still limitations.  His research is investigating the role of hyperthermic intracavitary chemotherapy.

Intracavitary chemotherapy allows for the chemotherapy to be directly administered to the cancer cells maximizing its efficacy and limits the toxicities (which lead to side effects).  Hyperthermia is believed to increase the effectiveness of chemotherapy.

Alimta (pemetrexed) is the chemotherapy being used in this research because it is highly soluble, has a short half-life, and is stable at high temperatures (42 degrees Celsius) while delivering a 41.3% response rate for those with unresectable disease. 

Animal studies show potential benefit.  Hyperthermic chemo may be given during surgical resection or with a VATS infusion which is currently a new clinical trial available at the University of Michigan.

 

Emerging Therapies

Anne Tsao, MD, MD Anderson Cancer Center

Identifying New Targeted Therapies for Malignant Pleural Mesothelioma

Dr. Tsao discussed some of the current research at MD Anderson Cancer Center in Houston, TX.  Some of this research includes the archival tissue bank which is collecting clinical data for specimens from 89 patients, including tumors, serum, and plasma.  Malignant pleural mesothelioma cell lines and mesothelial tissue lines have also been obtained from outside labs for research.

This data will be used in ongoing research testing chemotherapies.  Because mesothelioma causes abnormal capillary growth in the body and has poor lymphatic drainage, chemotherapies have not been highly successful.  The combination of Alimta and Cisplatin give the highest efficacy for patients with survival averaging 12.1 months. But research into a drug known as AZD2171 appears promising as does a clinical trial which will follow patients who undergo either a pleurectomy with decortication or the extra pleural pneumonectomy, followed by radiation and adjuvant chemotherapy if needed.  This trial pursues the most aggressive treatment approach.  Research into biomarkers is also ongoing.

Of interest to patients on Medicare, Dr. Tsao reported that Medicare is no longer paying for PET/CT scans; therefore MD Anderson will incorporate the PET/CT scans into their clinical trials.

 

Steven Albelda, MD, University of Pennsylvania Medical Center

Tumor Immunology and Immunotherapy

Dr. Albelda discussed the underlying problem of tumor development which is that the “tumor tricks the body into accepting it as ‘normal,’” which is due in part to the proteins which tumors have that prevent the body’s immune system from recognizing them as foreign and dangerous.

To combat this situation, chemotherapy can be used, but Dr. Albelda prefers finding a gentler system to treat mesothelioma, a system that uses the immune system.  One approach is to inject the immune system with interferon which alerts and stimulates the immune system while killing the tumor cells.  This could be accomplished by injecting an adenovirus into the tumor.  This gene therapy halts tumor development in three different areas:

• Directly prevents tumor cells from surviving and dividing.
• Activates the body’s natural immune responses
• Decreases blood supply to the tumor by preventing blood vessel formation (a process known as anti-angiogenesis)

Clinical trials testing this gene therapy are already underway.  The interferon injection is inserted into the pleural space.  Ten patients received a single dose and 13 received multiple doses of the injection.  Patients reported minimal side effects and more than one third had a favorable response.  Further clinical trials are scheduled to open at the Mayo Clinic at the end of 2008.

Further therapy targeting mesothelin are also underway.  Mesothelin is a protein often expressed on mesothelioma cells and using a specific antibody combined with a deadly poison, new therapies may be able to directly target mesothelioma cells.  In contrast, chemotherapy agents often kill healthy cells along with cancerous cells.  Dr. Albelda pointed out that a new anti-mesothelin monoclonal antibody known as MORAb-009 may be particular useful and works similarly to the drug Herceptin, which has been a break-through drug for breast cancer treatment.

Currently in clinical trial is a mesothelin tumor vaccine known as CRS-207, which “literally ‘vaccinates’ the body against the mesothelioma tumor.”  Results are not yet published.

Overall, Dr. Albelda believes immunotherapy for mesothelioma is very promising currently and future trials will be combined with existing therapies such as Alimta/Cisplatin chemo.  However, patients must be willing to participate in these trials in order to determine their efficacy.