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Lung Overdue

Progress in lung cancer is likely to stem from targeted treatments.

BY CHARLOTTE HUFF
PUBLISHED SATURDAY, MARCH 13, 2010
Mark Bailey has been riding the leading edge of non-small cell lung cancer treatment, benefiting from some of the latest advances, as researchers begin to better understand some of the malignancy’s genetic markers and related treatments. 

Bailey, who was diagnosed with stage 4 adenocarcinoma in September 2007, underwent several phases of treatment, beginning with brain and pelvic radiation to attack his advancing lung cancer, which included at least a dozen lesions in his brain. (The two primary tumors were located in his right lung.) Shortly after, he started taking a targeted drug, Tarceva (erlotinib), first in combination with chemotherapy as part of a clinical trial and then by itself for close to a year. In January 2009, Bailey’s oncologist at Ohio State University added another drug, Alimta (pemetrexed).

The retired law enforcement special agent credits Tarceva, among other measures, with buying him crucial months. Within six months after starting the drug, along with carboplatin and Taxol (paclitaxel), his lung tumors had shrunk to less than 10 percent of their original size, he says. “Without that drug, I don’t think I’d be here,” says the 40-year-old father of three.  

Targeted treatments, such as Tarceva, are among the more encouraging advances to emerge in non-small cell lung cancer treatment in recent years, according to researchers and physicians interviewed.

Other headway has been made in the difficult-to-treat malignancy, including advances in chemotherapy and maintenance treatment. But it’s insights into the role of biomarkers, specifically mutations in lung tumors themselves, that hold the most promise for patients in the years ahead, experts say. Already for some patients, genetic analysis is helping doctors select the drug that will best target the tumor’s vulnerabilities, says Nathan Pennell, MD, PhD, a lung cancer specialist and assistant professor of medicine at the Cleveland Clinic Taussig Cancer Center.

“We’ve really exhausted the capacity of traditional cytoxic chemotherapy to make a huge difference,” he says. “By and large, we’ve been trying to shift gears and go to a more targeted approach as our understanding of lung cancer changes.”

So far, the latest genetic findings are better news for never-smokers or people with a limited smoking history. The tumor mutations that have been identified, most notably in the epidermal growth factor receptor gene (EGFR), or more recently, ALK, are more common in non-smokers, and the presence of these markers provide targets for cancer treatment.

Improving the survival rates for non-small cell, the most common form of lung cancer, has presented a daunting challenge, primarily due to delayed diagnosis. Survival at one year, for all stages of malignancy combined, has increased somewhat from 35 percent in the late 1970s to 41 percent from 2001 to 2004, according to National Cancer Institute data. But the five-year survival rate, at 15 percent, hasn’t significantly budged.

“So far, these [targeted] drugs have had the most benefit in increasing the amount of time that people in stage 4 can live,” says Pennell, adding that those drugs that show effectiveness will be tested in earlier stages of lung cancer. “The hope is that they will also increase survival in the curable setting.”

Accounting for more than 85 percent of all lung cancer diagnoses, non-small cell lung cancer is comprised of two major types: non-squamous, including adenocarcinoma and large cell, and the second type, squamous carcinoma.

For the 15 percent of lung cancers found before the malignancy has spread beyond the lung, early diagnosis tends to occur accidentally, perhaps picked up on a pre-surgical chest X-ray. For never-smokers, like Bailey, it might take even longer. When Bailey complained of pain in his back, pelvis, and knees, doctors initially thought it was joint or muscle related. It wasn’t until Bailey experienced several days of vision and hearing problems, along with severe headaches, that an MRI of his brain identified the lesions there.

One difficulty with treating non-small cell lung ­cancer is, like many malignancies, it’s a mixed bag of diseases with various genetic underpinnings, says Adi Gazdar, MD, a professor of pathology and deputy ­director of the Hamon Center for Therapeutic Oncology Research at UT Southwestern Medical Center in Dallas. “You are talking about a lot of different subtypes, and so no single targeted therapy is going to work for all of them,” he says.

For years, the primary approach for patients with early-stage lung cancer has been surgery, when feasible. In cases in which the malignancy can’t be completely removed through surgery, radiation may be combined with chemotherapy prior to surgery. Radiation also may be delivered to limit the growth of the malignancy or to relieve symptoms in more advanced stages.

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