December 3, 2004

Less painful option for lung fluid buildup studied

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D. Brent Polk, M.D., is studying a protein that may one day have an impact on the treatment of inflammatory bowel disease.
photo by Anne Rayner

Less painful option for lung fluid buildup studied

While sitting in a Vanderbilt lecture hall several years ago, researcher Kirk Lane was bewildered by the quarter-century-old procedure of pleurodesis.

The procedure, which consists of injecting sterile dirt into the chest cavity of patients suffering from malignant pleural effusion, is one of three treatment options available to physicians. Although used for palliative care, each compound causes painful scarring that prevents fluid buildup.

Many kinds of cancers metastasize to the surface of the lung and the inside surface of the chest cavity, Lane said. Once there, these metastases cause fluid to accumulate. Called malignant pleural effusion, the lungs become compressed as the chest cavity fills with water, making it very difficult for the patient to breathe. Treatment for this ailment calls for the draining of the fluid from the chest cavity. In the majority of patients, the fluid returns requiring a procedure called pleurodesis — another draining in addition to the injection of a sterile irritant so that both the lungs and chest wall scar, fusing and preventing further fluid build up.

“When I first heard about this procedure, it was during a seminar at Vanderbilt,” said Lane, Ph.D., research assistant professor of Medicine. “They actually take talc, a mineral you dig up out of the ground, sterilize it and put it into the chest as an irritant. I said, 'This is the end of the 20th century and the best we can do is put dirt in people's chests?' It's sterile dirt, but it's still dirt and it's very painful.”

So Lane and several others began meeting to discuss ways to treat malignant pleural effusion with a biological compound that would create scars with less pain.

This team selected transforming growth factor beta or TGF Beta. The team has performed many studies in several animal populations since 1997 and the therapy has proven effective. A patent for the treatment was secured in 1999 and a two-year National Institutes of Health grant for $700,000 was recently awarded to the group and a local drug company, Cumberland Pharmaceuticals. The trial is expected to begin in early 2005.

“Malignant pleural effusion occurs usually secondary to breast, colon and lung cancers,” Lane said. “Patients who are in advanced disease of any one of these might be candidates for the trial. But this is not a cure. It is palliative. The issue for us is that all the treatments that are currently being used are very painful. Secondly, all the procedures currently being used require patients to spend more than a week in the hospital.

“Our treatment will require the same amount of hospitalization because it is an unproven therapy, but we envision that if this works like we think, this might be done on an outpatient basis in a doctor's office.

“In a 90-day lifespan, you would not lose one or two weeks of that in a hospital. This is purely a palliative procedure, with the biggest advantage being quality of life.”

Current therapies call for the use of talc, tetracycline and derivatives as well as bleomycin. These agents, all irritants, cause a chemical burn. TGF Beta, Lane said, is not an irritant and does not cause burns.

“What we believe it does and what the literature suggests it does is to form an immediate scar. There is no need to kill cells and create an irritant environment thereby needing a wound-healing process to occur to heal that wound. You circumvent making the wound and just make the scar.”

Another key benefit of using TGF Beta is its effectiveness. Current therapies take two weeks to work and have a 60 percent to 90 percent success rate while the TGF Beta agent has close to a 90 percent success rate and works in about five to seven days in animals.

Lane hopes to enroll about 24 patients in the blinded trial over an 18-month period. The study will continue for at least 90 days past the last enrollment. TGF Beta's safety in humans has already been evaluated because it has been used for other disease treatments. Now Lane must await the outcome of his trial to determine its effectiveness as a therapy for pleurodesis.

Lane, the principal investigator for this trial, has a proprietary interest in its success. With the patent already granted, if the treatment was approved and commercialized he would profit, as would co-inventor, Rich Light, M.D. professor of Medicine.

With the potential for conflict of interest, Lane intentionally recruited physicians to assist with the hands-on portion of the trial. Unbiased physicians will handle the data analysis and safety monitoring during the trial.