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Research finally increasing on rare asbestos-related lung cancer

August 3, 2015


BALTIMORE — While the use of asbestos peaked about 40 years ago, the number of cases of the rare but deadly cancer it causes has not declined.

Every year, doctors diagnose about 3,000 new cases of mesothelioma after patients come in with a cough, fever, fatigue, excessive sweating and pain in the chest. In most cases the disease already has advanced so far that patients will die in a matter of months.

Treatment is primarily palliative — meant to ease the suffering — but that may be changing.

Doctors see hope as interest in the disease has grown. There are at least 20 clinical trials underway, and the FDA recently gave a special designation to a new drug created by AstraZeneca’s Rockville, Md., subsidiary MedIummune.

"For the first time we have more companies than ever interested in this orphan disease," said Mary Hesdorffer, a nurse practitioner who is executive director of The Meso Foundation, which says it is the only nonprofit organization dedicated to ending mesothelioma and the suffering from it.

If any of the new drugs prove promising, it could extend the life of those who live with the disease.

"Really, treatment since the early 2000s has not changed for mesothelioma," said Dr. Julie Renee Brahmer, an associate professor of oncology and interim director at the Johns Hopkins Kimmel Cancer Center at Bayview, who is participating in some of the clinical trials. "Mesothelioma is such a slow-growing disease that it is insidious, and we need to find better ways to treat people."

The average mesothelioma patient will live only 7 to 17 months after diagnosis, doctors said. Only about 9 percent of patients diagnosed from 1975 to 2008 survived at least five years.

As a result most of the attention on mesothelioma has been on litigation rather than developing treatments. If the disease can’t be cured, the thinking goes, someone ought to pay.

Attorneys around the country, including Baltimore’s Peter T. Angelos, sued the companies who exposed workers and others to asbestos, the fire-resistant and insulating material that is mesothelioma’s primary cause. They’ve won large settlements for the victims and huge profits for themselves.

Today laws and regulations limit the use of asbestos, though it’s still found in some products such as roofing and brake pads. An entire industry has sprung up around removing asbestos from homes and buildings, where it was used to insulate walls and pipes.

There is only one drug combination treatment for the disease approved by the FDA. The chemotherapy drug pemetrexed works by blocking the action of a certain substance in the body that may help cancer cells multiply. It is combined with another chemotherapy drug called cisplatin, which can kill cancer cells, but doctors said more effective treatments are needed.

AstraZeneca announced in April that it received FDA orphan drug designation for its drug tremelimumab to treat mesothelioma. Intended to encourage the development of drugs that might not prove too profitable, the designation is given to drugs used to treat rare diseases and gives their makers extended exclusitivity to sell the drugs and tax credits for developing them.

Tremelimumab is part of the broad pipeline of immuno-oncology treatments under development by AstraZeneca and its biologics research and development arm, MedImmune, which are designed to harness the body’s own immune system to fight cancer. It also is being tested in combination with another drug to treat head, neck and non-small cell lung cancers.

In addition to researching this immunotherapy treatment, studies are looking at gene therapy, which attempts to add new genes to mesothelioma cells to make them easier to kill, according to the American Cancer Society. Researchers also are studying the use of specially designed viruses that could infect and kill the cancer cells directly, or cause the immune system to attack the cancer cells.

Many of these treatments are still in the early phases of clinical trials.

Hopkins’ Brahmer is involved in a trial testing a vaccine that attacks a protein on mesothemial cancer cells. She is also part of a study that targets cancer stem cells.

The rate of mesothelioma first began increasing significantly in the 1970s. Those in the medical community differ on when and if they think the disease has peaked. Some say it hit its high in the 1990s, while others said it may yet peak down the road.

"Because it is so rare the interest is not quite as great, but it does impact those people who have been exposed, as well as their families," Brahmer said.

Doctors sometimes confuse the symptoms of mesothelioma with other illnesses, such as asthma or pulmonary disorder. A correct diagnosis may not come until the disease is in the most advanced stages.

Jen Blair, a 43-year-old substitute teacher, said it took months for doctors to figure out what was causing severe pain in her abdomen in 2007. They blamed it on gynecological issues, and a family member even accused her of being a hypochondriac and suffering from postpartum depression. Finally, a CAT scan determined the truth.

Blair’s disease was caught early enough that it was removed with surgery. But it reappeared and she had to have a second surgery this past March. She worries about its return.

"I don’t know what my new normal feels like," she said. "The first time it took me like two years before I wasn’t skittish anymore."

In once predominantly blue-collar Baltimore, many cases of asbestos have been connected to jobs in shipbuilding, insulation, pipe fitting, auto mechanics and other manufacturing professions. Microscopic asbestos fibers easily become airborne and can be inhaled, lodging in the lungs and slowly damaging them.

Most people with the disease show symptoms many years after being exposed, well after companies have shut down or cleaned up asbestos.

"It doesn’t happen a year out and it doesn’t happen 10 years out," said Albert Polito, medical director at the Lung Center at Mercy Medical Center. "It’s like 30 to 40 years out in most cases."

Others may not know they have been exposed to asbestos until doctors, and sometimes lawyers, start asking their medical history. They may have been exposed at a school or an old apartment building.

Blair isn’t sure where she was exposed. She has been a teacher all her life and never worked in manufacturing.

The wives of manufacturing workers exposed to asbestos also have been known to get the disease, perhaps from cleaning clothes covered in the microscopic fibers. Some research also has found that people exposed to high doses of radiation to the chest or abdomen as treatment for another cancer have developed mesothelioma.

The disease is different than most cancers in that it doesn’t appear as raised tumors. The tumors are more flat along the lining of the lungs, making them hard to remove once they have spread. Doctors said it’s difficult if not impossible to remove all traces surgically.

"You are almost certainly going to succumb to the cancer at some point," said Dr. Joseph Friedberg, a mesothelioma expert who is the Charles Reid Edwards professor of surgery at the University of Maryland School of Medicine. "The goal is to try and buy you more time."

Friedberg, also head of thoracic surgery at University of Maryland Medical Center and thoracic surgeon-in-chief for the University of Maryland Medical System, recently came from the University of Pennsylvania, where he pioneered a lung-sparing surgical technique for mesothelioma and, along with fellow researchers, published some of the best results that have been reported for the deadly cancer.

Part of the treatment technique they employed involved the use of photodynamic therapy, a light-based cancer treatment that potentially stimulates the immune system against the cancer and is under further investigation.

He hopes to do even more advanced research at the University of Maryland, where he has created a mesothelioma program.

"We’re not where we need to be, not even close," Friedberg said. "But there is progress being made all around."

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