Mesothelioma is an aggressive cancer caused by asbestos exposure. The disease has a very long latency period and is often not discovered until decades later, after the disease has progressed to an advanced stage leaving patients with limited treatment options.  Chemotherapy is considered the most effective single modality for the treatment of mesothelioma. However, mesothelioma has shown to be chemo-resistant and the chemotherapy is primarily used to relieve symptoms.  

Ravi K. Amaravadi, MD, an assistant professor of Medicine at the Perelman School of Medicine and Abramson Cancer Center at the University of Pennsylvania, found that combining hydroxychloroquine (HCQ), a drug currently used in the treatment of malaria and rheumatoid arthritis, with cancer therapies, such as chemotherapy, “can enhance the antitumor activity of these drugs in laboratory models of treatment-resistant cancers.” 

Amaravadi and his team believe HCQ blocks autophagy, the process of “self-eating” within cells, and stops the continued growth of cancerous cells.  The researchers reported that autophagy is increased in cancer cells, and the cells might actually “be addicted to autophagy.” Autophagy, Amaravadi believes, is the way cancer cells evade chemotherapy. 

“While our knowledge of the role of autophagy in cancer is still in its infancy, the opportunity to learn about autophagy, both at the bench and the bedside, could accelerate the translation of basic advances in this field into clinical benefit for patients with cancer,” says Amaravadi.

According to the report, over 30 clinical trials have been initiated for HCQ to test the effectiveness of the drug with various cancers.  One clinical trial is underway to determine if adding HCQ to erlotinib helps in the treatment of non-small cell lung cancer.  Erlotinib is a tyrosine kinase inhibitor which is shown to block a protein called the epidermal growth factor receptor which is found in lung cancers. 

In a separate study, researchers at Johns Hopkins found that compared with lapatinib, erlotinib appeared to prevent altered EGFR from working.  They concluded “erlotinib is a better drug treatment for non-small cell lung cancers that are associated with altered forms of EGFR protein.” 

Nearly 3,000 Americans are diagnosed with mesothelioma each year. Many of them rely on clinical trials for the opportunity to receive new, potentially curative therapies. 

The Penn findings were reported at the annual American Association for Advancement of Science meeting being held this week in Vancouver, British Columbia.

Mesothelioma is an aggressive, incurable form of cancer primarily caused by exposure to airborne asbestos fibers. Close to 3,000 Americans are diagnosed with the cancer yearly, with veterans accounting for nearly 30 percent of all cases of mesothelioma. Although there is no cure for mesothelioma, the symptoms can be treated with varying degrees of success through the use of surgical procedures, chemotherapy and radiation. 

The Transforming the Regulatory Environment to Accelerate Access to Treatments (TREAT) Act, introduced by Hagan, is targeted toward getting treatments in a quick and safe manner to patients with orphan diseases.  

“For patients suffering today from rare diseases for which there are no current treatments, medical advances can’t come fast enough,” said Hagan.  

According to Hagan’s press release, the TREAT Act accelerates the review and approval process for medicines that:

• treat an unmet medical need,
• significantly advance the standard of care, or
• are highly targeted therapies for serious or life-threatening diseases or conditions. 

The Act aims to give the U.S. Food and Drug Administration (FDA) the tools necessary to transcend existing barriers, reform its processes, and provide greater clarity, consistency, and transparency to industry.  With the proper tools, Hagan hopes the FDA “can positively influence our national strategy to identify and treat serious and life-threatening diseases and improve the quality of life for millions of Americans.” 

The National Organization for Rare Disorders (NORD) issued a statement in support of the TREAT Act.   NORD President and CEO Peter L. Saltonstall said, “We are grateful to Senator Hagan and her staff for listening to the concerns and needs of the patient community.  We look forward to supporting their efforts as this bill makes its way through Congress.” 

The changes to the FDA enacted under TREAT are in addition to the latest changes announced by the FDA in support of rare diseases.   Last year the FDA introduced its performance goals for 2013 through 2017 for the Prescription Drug User Fee Act (PDUFA). PDUFA is also aimed at advancing the development of drugs for rare diseases. 

“There is no time to wait. If we can accelerate the [approval] process, that’s what we need to be doing,” said Hagan of her motivation behind introducing TREAT. 

Nearly 30 million Americans, or one in 10, are diagnosed with a rare disease.  According to government statistics, between 85 and 90 percent of orphan diseases are serious or life-threatening, yet only about 200 of them currently have any effective treatments.  Government support in advancing treatments for these diseases is critical to the medical community.

Mesothelioma is a rare, aggressive form of cancer primarily caused by exposure to airborne asbestos fibers.  Each year close to 3,000 Americans are diagnosed with the incurable cancer. While there is currently no known cure for the disease, many clinical trials and studies are underway that could offer hope to mesothelioma patients through discovery of new approaches to treat the disease, to develop procedures to detect the disease at an early stage and to find a cure.   

“This year we have awarded another half million dollars toward the search for a cure. Our mission to cure meso is clear and we won’t stop until it’s accomplished,” said Kathy Wiedemer, the executive director of the Meso Foundation.

This year’s funded mesothelioma projects are:

• Tao Dao, MD, PhD, Memorial Sloan Kettering Cancer Center – TCR-like mAb specific for WT1 peptide/MHC complexes on mesothelioma
• Assunta DeRienzo, Brigham and Women’s Hospital – Identification of Novel Mutations in Malignant Pleural Mesothelioma using Deep Whole-Genome Sequencing
• Marc Ladanyi, Memorial Sloan-Kettering Cancer Center – Frequent inactivation of BAP1 in mesothelioma: biology and new therapeutic opportunities
• Liang-Chuan S Wang, Perelman School of Medicine at the University of Pennsylvania – The Role of the IFN response in Chemosensitivity of Mesothelioma to Pemetrexed
• Nadia Zaffaroni, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy – Identification and validation of miRNAs as novel biomarkers and therapeutic targets in diffuse malignant peritoneal mesothelioma 

The five new grants will bring to 76 the total number of grants funded by the Meso Foundation.  The grants were selected from among 46 applications.  The Mesothelioma Applied Research Foundation instituted its grant funding program in 2000 and has since awarded over $7.6 million to critical research, stimulating the field of mesothelioma research and encouraging scientists to devote their life-work to this under-researched cancer.

Eternit Heads Responsible for Deaths and Illnesses
According to ChannelNewsAsia.com, over 3,000 workers of the Eternit cement plants died from mesothelioma or other asbestos-related illnesses, and countless others have been sickened by the toxic material.  Asbestos was one ingredient used in making the cement.

Asbestos is a known carcinogen that has been linked to respiratory diseases, including asbestosis, lung cancer and mesothelioma, a cancer of the lining of the lungs that claims the lives of approximately 3,000 Americans each year.   Nearly every European country, as well as the United States, have safety regulations in place for handling asbestos and asbestos-containing products to protect workers.

The former owner of the company and a major shareholder in the company were found “guilty of causing an environmental disaster and failing to comply with safety regulations.” In addition to their jail time, the two were ordered to pay 30,000 euros (approximately $39,000) in damages to relatives of people killed by asbestos-related diseases, and 35,000 euros for every sick person.  The payouts are expected to total tens of millions of euros.

Asbestos-Related Illness is a Tragedy
Unfortunately, the risk of contracting mesothelioma is a life-long risk once exposed to asbestos.  Symptoms of mesothelioma, such as shortness of breath and chest pains, may take as many as 10 to 50 years to develop after a person has been exposed to the mineral. Once diagnosed, mesothelioma progresses rapidly.   Although there is no cure for mesothelioma, symptoms can be relieved through the use of surgical procedures, chemotherapy and radiation.

The lead prosecutor in the Italian asbestos trial, Raffaele Guariniello, said in his closing speech in November, “I have never seen such a tragedy. It affects workers and inhabitants… it continues to cause deaths and will continue to do so for who knows how long.”

Mesothelioma Litigation Offers Financial Protection to Victims
Asbestos litigation is the longest running mass tort in U.S. history, with the first case filed in 1929. Hundreds of thousands of people in the United States have filed lawsuits against thousands of defendants after being diagnosed with mesothelioma, asbestosis or other asbestos-related diseases.

Many people that do not understand the devastating impact mesothelioma can have on a family believe that mesothelioma lawsuits are frivolous.  What may not be clear, however, is that some companies broke laws, tried to hide information and failed to provide adequate protection to their employees – all while knowing mesothelioma was a real risk to their employees.

Italy’s Health Minister Renato Balduzzi said in a statement after the verdict, “It is not a local battle [against asbestos], but a national one, a worldwide one. The Turin verdict shows that Italy is doing its part,” he said.

Last year, the New York law firm of Belluck & Fox, LLP, secured separate verdicts in the United States totaling $32 million and more than $19 million in cases involving individuals who contracted the deadly disease, mesothelioma, after being exposed to asbestos.  The companies in the lawsuit were found to have acted with reckless disregard for the safety of others.

Some doctors estimate that mesothelioma treatment can cost anywhere from $150,000 to $1 million, depending on the number of doctors’ visits, cost of surgeries and lengthy hospitalizations, chemotherapy and radiation therapy.  Most individuals, even with insurance coverage, cannot afford the high cost of treatment for the disease.  Compensation from companies can help cover some, if not all, of the associated costs.

Although mesothelioma is only known to occur as a result of exposure to asbestos, a disproportionate number of mesothelioma cases were diagnosed among miners, and their families, in the Minnesota Iron Range taconite mine.  Pleural mesothelioma is one of the most aggressive and deadliest forms of cancer, with limited treatment options.   While chemotherapy and radiation are most often used to relieve symptoms, the cancer often metastasizes leaving the patients with a very short survival time.  

“We’ve taken a new viral agent, repositioned it for this disease and are advancing it toward the clinic as an entirely novel treatment,” says Stephen Russell, M.D., Ph.D., Mayo Clinic molecular researcher who conceived the idea of using the measles virus vector against mesothelioma.  Russell outlined the research in Mayo’s online magazine, Discovery’s Edge. 

In preliminary studies, when mesothelioma-infected mice were injected with the virus their life span doubled compared to the cancer stricken mice that did not receive the virus.  Researchers further found that some mice appeared to have been cured. 

The encouraging findings led the researchers to open the phase I clinical trial to 12 -36 patients.  A group of the mesothelioma patients will receive the MV-NIS (measles virus) dose, injected into their chest cavities through catheters that also serve to drain excess fluid caused by the disease from around their lungs. 

The researchers are hopeful that tumors will shrink significantly, and side effects will be minimal. 

“Because of the data Mayo has on the safety of MV-NIS when used for ovarian cancer, we don’t anticipate any surprising effects,” said clinical trial lead Robert Kratzke, M.D., of the University of Minnesota. “The only effects we don’t know would be anything specific to putting the virus into the chest cavity as opposed to the abdominal cavity.”  

The clinical trial will determine effective dosing for the treatment.  In the future, the measles virus could be combined with chemotherapy treatments “to provide a one-two punch.”   

Currently, there is no known cure for mesothelioma.  If this novel treatment proves as successful on humans as on mice, it could be the breakthrough all mesothelioma sufferers and their physicians have been waiting for.  Estimated completion date for the trial is November 2013, and mesothelioma specialists will surely be anxiously awaiting the results. 

For more information on this promising study see ClinicalTrials.gov.

In an interview with Pharmaceutical-Technology.com, Alastair Kent of Genetic Alliance UK, Tim Cote of the National Organization for Rare Disorders and Dr. Steve Groft of the Office of Rare Diseases Research all agreed, that even though most pharmaceutical companies are slashing their R&D budgets, rare disease drug development should not be affected.

This is great news for not only those suffering from rare diseases, but for the International Rare Disease Research Consortium (IRDiRC) formed last year with a goal to develop “200 new rare disease treatments by the year 2020 and the development of diagnostics for all rare disorders.”  The consortium realized that between 85 and 90 percent of orphan diseases are serious or life-threatening, but they typically get scant attention from researchers and pharmaceutical companies.

When the U.S. National Institutes of Health and the European Commission joined forces to form the Consortium, the organization invited companies and researchers to join in the mission to find treatments where none exist. Mesothelioma treatments typically consist of chemotherapy and radiation, however, the progression of the disease can rarely be stopped, and survival is often less than a year.

The trio interviewed for the article believe that companies now need to “follow the science” in order to continue to innovate and be profitable.  And, according to Cote, “science is taking us into the area of large molecules and small populations.”  Cote believes that there will be more clinical trials for rare diseases because, “The size of clinical trials for orphan drugs historically has been much less, so the costs of doing the clinical trials are considerably lower.”

Large pharmaceuticals, the three noted, still have to adjust to the changing marketplace, and they must also “unlearn the fact that it’s impossible” to succeed in the development of drugs for the orphan disease population.  They say currently large companies may need upwards of $400 million to develop a drug, whereas small companies can develop a drug for just $10 million.

In the United States an orphan disease affects less than 200,000 Americans at one time.  In Europe, a rare disease affects fewer than 5 in 10,000 Europeans.  While the number of people with mesothelioma and the other diseases may be relatively few, the disease is just as real as one affecting thousands more. Rare disease sufferers deserve the full focus of researchers and the pharmaceutical companies, and seeing the shift to focus on rare diseases brings hope to many patients who feel neglected by the industry.

Lung cancer is the second leading cause of death in the United States and afflicted 157,300 Americans in 2010, according to federal statistics.  According to the Van Andel Research Institute, smoking accounts for nearly 85% of the cases of lung cancer, while environmental hazards, such as asbestos and radon, and genetic factors account for the remaining 15%.

Mesothelioma is a form of lung cancer caused by breathing in the asbestos fibers that then become lodged in the thin membrane that lines and encases the lungs.  Currently, mesothelioma is considered incurable and the prognosis is often less than one year.  Close to 3,000 people in the U.S. are diagnosed with mesothelioma each year.

Through ongoing research, physicians and scientists hope to uncover new approaches to treat and diagnose lung cancer and mesothelioma.  Surveys, such as this one, provide valuable information to researchers directly from the medical professionals that deal with the deadly cancers on a daily basis.

Questions on the survey include inquiries about the percentage of patients with lung cancer managed by the survey respondent; chemotherapy agents prescribed, such as the combination of cisplatin/pemetrexed or carboplatin/pemetrexed; whether cases are discussed in multi-disciplinary meetings and if the respondent follows ESMO Clinical Practice Guidelines.

The electronic survey, which will be open until the end of February, takes about five minutes to complete.  The project is being led by Dr. Raffaele Califano from The Christie NHS Foundation Trust in Manchester.  The YOC hopes to present its findings at the ESMO congress in 2012.

ESMO is the leading European professional organization committed to advancing the specialty of medical oncology and promoting a multidisciplinary approach to cancer treatment and care.  Through their extensive fellowship program young oncologists get the opportunity to “gain valuable research experience and skills and also have the opportunity to disseminate information in their home countries.”

Empowering patients to take charge of their treatment is an important step in cancer care. “You are in charge of your own health, and you are your best health advocate,” says Elizabeth Cohen in her book, “The Empowered Patient: How to get the Right Diagnosis, Buy the Cheapest Drugs, Beat Your Insurance Company, and Get the Best Medical Care Every Time.”  However, taking charge could lead a patient down the wrong path if that patient is not fully informed. 

Mesothelioma is a fatal cancer of the lining of the lung and abdomen that has been directly linked to asbestos exposure.  Treatment often includes chemotherapy and radiation, but researchers have recently begun focusing on patient-centric care with treatments targeting the patients’ unique characteristics.  Personalized mesothelioma care optimizes the potential for success.  An effective personalized plan requires full disclosure from both the patient and the physician. 

Data recently compiled from a 2009 survey of 1,891 U.S. physicians, and published in Health Affairs, found “behavior that is in conflict with at least some of the tenets of the Charter on Medical Professionalism,” according to an article in News @JAMA.   In the survey, the doctors were asked questions regarding honesty as laid out by the Charter.  The Charter, according to the survey authors, “requires openness and honesty in physicians’ communication with patients.” 

The survey found that more than half of physicians in the previous year had described a patient’s prognosis in a more positive manner than warranted.  In addition, 20% of the physicians surveyed did not completely agree that a doctor should always tell the truth.  In fact, 10% admitted to telling a patient “something untrue” in the previous year. 

The authors concluded that their findings “raise concerns that some patients might not receive complete and accurate information from their physicians, and doubts about whether patient-centered care is broadly possible” unless physicians focus more on open, honest communications. 

Study lead, Lisa Iezzoni, MD, MSC, professor of medicine at Harvard Medical School and director of the Mongan Institute for Health Policy at Massachusetts General Hospital, in Boston, admitted that there are different reasons for doctors to not be fully truthful.  However, she said, “at the end of the day, patients need accurate information about their health.” 

In January 2011, the American Society of Clinical Oncology published guidelines encouraging physicians to discuss a patient’s treatment options and preferences immediately after their terminal diagnosis so the treatment can be individualized from the start.  The guidelines pointed out that physicians should assess a patient’s options, goals and preferences early in his treatment.  This conversation cannot happen if the doctor has not given the patient an honest prognosis.

Close to 3,000 new cases of mesothelioma are diagnosed each year in the United States. Although there is no cure for mesothelioma, it can be treated with varying degrees of success through the use of surgical procedures, chemotherapy and radiation. The prognosis for mesothelioma patients is usually grim, with the average survival time varying from 4 – 18 months after diagnosis.

For years, medical professionals, environmentalists, lawyers, and others affected by the tragedy of asbestos exposure, have been calling for a ban of asbestos.  The only way to eliminate the deadly asbestos-caused diseases is to eliminate exposure to the deadly toxin.  In fact, in December the U.S. Environmental Protection Agency issued a warning saying, “asbestos is a human carcinogen with no safe level of exposure.” 

In a prepared statement, Linda Reinstein, co-founder and president of the Asbestos Disease Awareness Organization (ADAO), said she “was appalled and shocked to discover” that according to the report, U.S. industries consumed 1,100 metric tons of asbestos from January through July 2011, compared to 820 metric tons during the same period in 2010. The difference represents a 34 percent increase in consumption. 

The report indicates that the use of asbestos in 2011 and the preceding 5 years is the lowest it has been in the United States since 1909. Further, the USGS reports that in 2011, U.S. apparent consumption increased by 6%, but it is unlikely to represent any resurgence in the asbestos industry. The report suggests that based on current trends, U.S. asbestos consumption is likely to remain near the 1,000-ton level in the near future. 

The US relies 100% on asbestos imports.  The primary sources are Canada (92%) and Zimbabwe (6%). 

Reinstein issued an appeal to Congress and President Obama, saying: “On behalf of the Asbestos Disease Awareness Organization (ADAO), I am calling on Congress and the President to immediately prohibit the importation of raw asbestos and asbestos-containing products from crossing our borders to protect public health. I have lost my husband, Alan, to Mesothelioma, a disease caused from asbestos exposure. Nothing can bring him or the hundreds of thousands of other victims back to life, but we can begin by aggressively preventing exposure thus eliminating deadly diseases.” 

Symptoms of mesothelioma such as shortness of breath, pain in the chest, and a persistent cough, often appear 20 to 50 years after exposure. Most cases of mesothelioma are not diagnosed until symptoms appear and the disease has progressed to an advanced stage leaving the patient with life-threatening complications.  Once the disease has reached an advanced stage, median survival is often less than one year.

ADAO was founded by asbestos victims and their families in 2004.   ADAO seeks to give asbestos victims and concerned citizens a united voice to raise public awareness about the dangers of asbestos exposure. ADAO is the largest independent organization dedicated to preventing asbestos-related diseases.

Asbestos is a known carcinogen and is proven to cause lung cancer, asbestosis, mesothelioma, a serious cancer caused by breathing in the asbestos fibers that then become lodged in the thin membrane that lines and encases the lungs, and other respiratory diseases.  Even small amounts of asbestos and infrequent exposure can create a risk for contracting mesothelioma or other asbestos-related diseases. 

According to the Yorkshire Post, two sisters in the family just died of mesothelioma caused by secondhand exposure they had to asbestos decades ago.  The other siblings suffer from pleural plaques, emphysema and scarred lungs. They are also still at risk of developing mesothelioma. Their father worked at Cape Asbestos in Hebben Bridge, Yorkshire from the 1930’s through 1958.  He died of lung cancer 10 years after leaving the company. 

The family recalled that they would play with their father when he returned home from work with his clothes still covered in asbestos dust. “I remember my mother shaking his overalls and dust going everywhere,” said one sibling. She added that as children they would sometimes accompany their father to work on Sunday and would play in the piles of asbestos dust. 

Most cases of mesothelioma are diagnosed 30 years or more after exposure. Currently there is no known cure for mesothelioma, and the average survival time varies from 4 – 18 months after diagnosis. According to Professor Julian Peto, of the London School of Hygiene and Tropical Medicine and the Institute of Cancer Research, the UK now has the highest death rate in the world from mesothelioma, with over 2,000 deaths a year.