WEDNESDAY, Sept. 28, 2005 (HealthDay News) -- Gleevec, a medication experts have hailed as a wonder drug in the fight against certain cancers, may also come to the rescue of patients battling lethal pulmonary hypertension.
According to a case study in the Sept. 29 issue of the New England Journal of Medicine, a 61-year-old man suffering from an advanced case of the disease saw his condition improve and stabilize after taking Gleevec (imatinib) -- even though all other medications had failed.
"Only the addition of Gleevec was able to prevent further deterioration, and even improved his condition," said co-researcher Dr. Hossein A. Ghofrani, of University Hospital Giessen, in Germany.
Although a single case report does not warrant widespread use of Gleevec for pulmonary hypertension, the German researchers who wrote the report said they are now planning a large clinical trial.
"I think a trial is a wonderful idea," said Dr. Richard Stein, a professor of clinical cardiology at Albert Einstein Medical College in New York City, and a spokesman for the American Heart Association. "Hopefully, we'll be able to make a real difference for these people."
According to Stein, pulmonary hypertension occurs when blood pressure mounts to dangerously high levels in the pulmonary artery, which carries blood from the right side of the heart to the lungs. The relatively common condition can occur for many reasons, but most often arises as a byproduct of other pathologies, such as heart disease and various lung ailments. Under the strain of these conditions, the pulmonary artery thickens and stiffens, causing blood pressure to rise.
"Right now, we have two classes of drugs that seem to be improving outcomes," Stein said. These include prostaglandin-linked compounds such as prostacyclin, and, more recently, another potent vasodilator -- Viagra (sildenafil). Both drugs work by relaxing and opening narrowed vessels.
"None of these medications cure the disease or give the patient a normal life back," Stein noted. "But most can prolong quality-of-life time before they get very sick." Patients with very high pulmonary blood pressures usually don't live past a year, he said.
In the German case report, the patient was diagnosed with just such a case of advanced pulmonary hypertension, this time a rarer, "primary" form of unknown origin. Standard therapies such as prostacyclin and Viagra proved useless, and the man's condition continued to deteriorate.
"In this desperate situation, we decided to initiate compassionate treatment with daily administration of 200 milligrams of oral imatinib mesylate (Gleevec)," given on top of the other medications, the researchers explained.
The change in the man's condition was dramatic.
By three months, his condition had improved "impressively," the researchers said, allowing him to become much stronger and more mobile than before Gleevec. That improvement has continued to the six-month point, they add.
The therapy appears to be working in other patients, too. "We have [successfully] treated more than 20 patients so far, all of which had no other therapeutic options or who were waiting on the transplant list for a new organ but appeared to run out of time," noted co-researcher Dr. Friedrich Grimminger, also of Univerity Hospital Giessen.
How did a drug best known for curing chronic myelogenous leukemia beat back hypertension?
Unlike the other drugs, Gleevec does not appear to work by dilating blood vessels, according to the researchers. Instead, the key to its effect lies in a phenomenon shared by both cancer and pulmonary hypertension.
"In cancer, tissue proliferation is uncontrolled and leads to the spreading of the tumor," Grimminger explained. "In pulmonary hypertension, also, uncontrolled growth of the vascular wall is the underlying mechanism of the disease."
"Gleevec is a drug which suppresses uncontrolled growth of tissue by specific blockade of the so-called tyrosine kinase pathway," he added. "We have proven that this pathway also plays an important role in the course of pulmonary hypertension. Due to these similarities, the anticancer drug Gleevec also works in progressive pulmonary hypertension."
This mechanism made sense to Dr. Norman Edelman, chief medical officer at the American Lung Association.
"What happens in response to hypertension is that vessels get thicker," he said. "The assumption is that [Gleevec] reverses that. So this treatment does have biologic validity, it's plausible."
In fact, because tissue proliferation is a hallmark of other serious illness, Gleevec's uses might expand even further, according to researcher Ghofrani. "Our current findings might open the door to a completely new therapeutic field of targeted treatment for chronic proliferative diseases such as atherosclerosis, COPD, lung emphysema or lung fibrosis," he said.
Right now, the emphasis is on pulmonary hypertension, however. "A large worldwide clinical trial is about to be conducted under our scientific lead," Ghofrani said. Besides testing Gleevec's safety and effectiveness, "we also hope to answer the question [of] whether the drug also works in earlier stages of the disease," he noted.
Stein stressed that, right now, experts have "just one report of the drug being effective." But he's hopeful that the results seen in this patient will be repeated in the upcoming trial. If that's the case, "Gleevec may turn out to be a valuable third product that we can use for these people," he said.
To learn more about pulmonary hypertension, head to the American Lung Association.