Nashville: A National Leader in Lung Cancer Research on Nashville Medical News

Nashville: A National Leader in Lung Cancer Research

By: SHARON H. FITZGERALD

David Carbone, Vanderbilt-Ingram Cancer Center's SPORE in Lung Cancer Program Director

Is it any surprise that more nicotine patches will be sold in the United States this month than in any month of the year? As Tennessee smokers again try to live up to their New Year's resolution to break their tobacco addiction, perhaps they should consider this: "Lung cancer kills more people than breast, colon, prostate and stomach cancer all put together. It's kind of the silent killer, because people don't realize what a problem it is," David Carbone, MD, said. "And the survival is so poor that there are few survivors to tell us about it. The five-year survival for all comers is less than 15 percent, but survival for all comers with prostate cancer is 90 percent, and with breast cancer it's 70 or 80 percent."

Carbone is the program director for the Vanderbilt-Ingram Cancer Center's SPORE in lung cancer. SPORE stands for Specialized Programs in Research Excellence, a National Cancer Institute designation to promote interdisciplinary research and translate discoveries to patient treatment. One of only six SPOREs for lung research in the country, Vanderbilt-Ingram recently received an NCI five-year grant of $12 million.

Lung cancer patients in the Nashville area are afforded rare treatment opportunities, thanks to the presence of Vanderbilt-Ingram and the Sarah Cannon Research Institute, an industry leader in clinical trials. Since its founding in 1993, Sarah Cannon has conducted nearly 200 trials in lung cancer alone. Currently, the institute has 15 active lung cancer trials with 11 more in the offing, according to David Spigel, MD, Sarah Cannon director of lung cancer research. "Patients in Nashville are fortunate to have so many opportunities in this region without having to travel so far to other sites," Spigel said.

At Vanderbilt-Ingram

SPORE funds finance five independent projects, plus career development and training of future lung cancer researchers. Carbone said two projects are in trial now, while a third is approved and will commence this year. "One of the themes of our research here in general is to identify specific patients who would benefit from specific therapies. It's called personalized medicine," he said.

One active clinical trial examines a subset of lung cancer patients whose tumors appear dependent on an enzyme called cyclooxygenase-2 (COX-2). In those cases, a COX-2 inhibitor and chemotherapy can be an effective treatment. "Yet it's been hard in the past to know which patients would benefit, so we developed a urine test, and we find that we can measure the activity of this enzyme," thus identifying patients who would benefit, Carbone said.

A second active trial looks at several different markers, including protein and DNA patterns in tumors, to try to predict the best therapy for individual patient tumors. The project is led by Vanderbilt-Ingram and is being conducted at six other sites nationwide as well.

The newest project, to open soon, examines a tumor protein dubbed a "notch" gene. "We will be characterizing patients for the presence and activity of this notch protein, which seems to be active in at least 40 percent of lung cancers. We've got some very exciting data with some brand-new drugs that we've developed against this protein, but they're not quite ready for human use yet," Carbone explained.

Yet another area of lung cancer study at Vanderbilt-Ingram is development of a blood test for lung cancer. "One of the problems with detecting nodules on a screening CT scan, for example, is that a lot of those nodules turn out not to be cancer, and you can't go ahead and take out people's lungs for every nodule you see," Carbone said. "So we're working hard to develop a blood test, and we actually have one that's only about 75 percent accurate. We would like it to be better than that, but it's still better than guessing."

Carbone estimated that 25-to-30 patients at any given time are involved in Vanderbilt-Ingram lung cancer trials, not counting the many more who remain in follow-up care.

At Sarah Cannon

Sarah Cannon is one of the nation's largest community-based research programs, boasting a network of hundreds of physicians, even in rural areas, whose patients can participate in the institute's clinical trials. "I just don't think there's anyone who does what we do in a community setting," Spigel said, adding, "It just so happens that because of our history and our size, we're pretty successful at putting patients on those studies. We tend to lead the U.S. in accrual of patients for trials."

Because Sarah Cannon isn't an academic institution, it doesn't pursue federal grants. Its trials, funded by pharmaceutical companies, fall into two categories: industry-sponsored studies initiated by a drug company and investigator-initiated studies "pitched" to a drug company by researchers like Spigel.

"Literally, not a day goes by when I don't scratch my head at the end of the day and say, 'Why do we do that? Is there a better way?' And then I think about whether we can design a trial to help solve the question," he said. "That's gratifying to come up with an idea that you hope is important and to then conduct a study – get it open, enroll patients on it and then get your results and hopefully have good results and move the field forward. That's what research is all about, trying to make incremental changes."

Spigel said this "nimble" approach is what lured him from the academic arena to Sarah Cannon in 2003.

Recently accepted by a drug company was a Sarah Cannon proposal for a clinical trial on lung cancer patients whom Spigel said are "underserved," those patients who generally are excluded from trials because they are weaker and usually older. "This group has not been studied well in clinical trials historically anywhere, because the sicker you are, the more likely that you will have some extra side effects," he said.

Sarah Cannon is already running a trial across the country in elderly patients, 70 and older, for a drug that interferes with how blood vessels feed cancers. Another large study, about to wrap up, has been investigating the possibility of treating lung cancer patients with two pills and no chemotherapy. One pill, called Tarceva, is already approved for lung cancer, while the other, called Nexavar, is approved for the treatment of kidney and liver cancer, but not lung cancer. "The most exciting part is helping patients avoid chemotherapy … to make therapy easier without excessive toxicity," Spigel explained.

While there's a lot of good news when it comes to future lung cancer treatments, Spigel did note that pharmaceutical companies are slowing the pace of studies they will fund. "Actually, when I first started here, there used to be a lot of 'yeses.' Lately, with the economic environment, it's a little bit harder. Companies are much more selective about how their funds are spent," he said.