Focusing on New Targets in Lung Cancer
Although lung cancer gets less attention than other, more treatable cancers, it has touched the lives of most people. One million cases of lung cancer are diagnosed worldwide each year, and patients and doctors have had few advances in lung cancer treatme
Recently, however, some headway has been made in the treatment of non small cell lung cancer, which is the type of lung cancer that affects most people. Today, chemotherapy is an option for more patients, and new, targeted therapies designed to zero in on cancer cells are now being used in some patients.
Survival rates for lung cancer are still low compared to those for other common cancers, such as colon cancer and breast cancer, largely because it is diagnosed in its late stages. The best approach is prevention, and quitting smoking can significantly reduce risk of lung cancer and other lung conditions, though factors such as the number of years you smoked, the age at which you became a smoker and whether you already had an illness when you quit, all play a role in risk.
Oncologists say there is room for optimism about treatment as well. Below, Joan Schiller, MD, a medical oncologist and a professor at the University of Wisconsin in Madison, offers an overview of treatment for non small cell lung cancer.
What are of the common types of lung cancer?
There are four major types. However, three of them act so much the same that we tend to call them by one name, and that name is non small cell lung cancer. The three subtypes under non small cell lung cancer are adenocarcinoma, large cell carcinoma and squamous cell carcinoma. The fourth type is called small cell lung cancer, which is more rare but tends to grow and spread more quickly than the other three types. It's also more responsive to chemotherapy. The theory is that most of the chemotherapy that we use works best on cells that are rapidly dividing. And since this is such a fast-growing cancer, cells are dividing particularly quickly, so the chemotherapy works better.
Are most people with non small cell lung cancer smokers?
About 15 percent have never smoked. Another 40 percent have quit smoking. So the majority of lung cancers these days occur in people who are not currently smoking. The lungs go close to being back to normal after you quit, but are not quite normal. Still, the biggest thing you can do to reduce your risk is stop smoking.
How is non small cell lung cancer usually discovered?
The most common way it appears is with a cough and shortness of breath. Typically, patients come in to the doctor's office and get treated for some type of upper respiratory tract infection, and then it's only when these symptoms don't go away that a chest X-ray is eventually taken.
What's the first step in treatment?
The first step is to make a diagnosis and that's usually done by some type of biopsy. The second major step is staging the cancer, which means figuring out how far has it spread, because that will ultimately determine what the appropriate treatment is. When it comes to non small cell lung cancer, we have four general stages. Stage I is the smallest and the one that has spread the least, and then you get to stage IV, where the cancer has spread outside the chest to other parts of the body. Stage I is operable and much more curable than stage IV, which is not operable.
What happens during surgery?
The surgeon usually removes not only the tumor but the lobe of the lung in which the tumor resides because there might be a small number of cancer cells elsewhere in the lobe. The right lung's got three lobes, the left lung has two lobes. That's called a lobectomy. In addition, the surgeon should also sample lymph nodes near the heart to see if the cancer has spread to those lymph nodes.
What is the recommended treatment for people with early-stage lung cancer?
We used to think that they only needed surgery. However, it turns out that even some patients with stage I lung cancer can have the cancer come back several years after the operation. So, presumably, in those cases, the cancer cells have escaped outside the tumor before the operation. What we've learned recently is that that certain people are more likely to be cured with chemotherapy after surgery than surgery alone.
At our recent annual meeting at the American Society of Clinical Oncology, there were two very large studies presented that definitely showed that adjuvant (post-surgery) chemotherapy is helpful for certain patients with stage I cancer. Stage I is usually broken up into two groups, Ia and Ib. Stage Ia is very small tumors and Ib is larger tumors. We haven't studied chemotherapy in the very small tumors yet, but for the Ib tumors, new data suggested adjuvant chemotherapy's helpful. This data also supports using adjuvant chemotherapy for stage II.
These two studies specifically reported a 10 to 15 percent improvement in survival at four to five years.
What patients receive radiation therapy?
Radiation therapy is often used for stage III disease. So stage III diseases means large, bulky tumors that haven't obviously spread outside the lung, but, on the other hand, they're so big and bulky that they're often very difficult to take out surgically. So, for those types of tumors, we tend to use chemotherapy, in case there are micrometastases elsewhere in the body, and then radiation therapy, where you aim external X-ray beams at one big spot.
The other place where radiation therapy is used is to relieve symptoms in stage IV cancer. So, if a tumor is in a particular area that's causing problems (for example, the bone is causing pain), then they can aim a beam of radiation specifically there.
Is chemotherapy ever given before surgery?
Because people with stage III disease present with such big, bulky tumors, they're difficult to take out surgically. Another approach that's of interest is giving chemotherapy with or without radiation first and seeing if you shrink the tumor and then thus make it operable. And that's an active area of research as well.
What is targeted therapy?
This is a word for drugs that attack pathways specific for cancer cells. Over the past 20 or 30 years, we've learned what makes a cancer cell different from a normal cell. And we're finally able to make drugs that target those specific things that make a cancer cell a cancer cell. One of the advantages of these targeted therapies is, because they don't target normal cells, they're going to have a lot fewer side effects. So there's a lot of interest in using these targeted therapies for all stages of lung cancer, stage I through IV.
The lung cancer drug Iressa is a perfect example of that. Many cancer cells need particular growth factors to live, and one of the growth factors that has been studied a lot recently is a growth factor called epidermal growth factor or EGF. This growth factor binds to a receptor on the cancer cell that activates the receptor and that, in turn, causes a cascade of events within the cancer cell that eventually causes it to grow. Iressa is thought to work by blocking activation of this receptor.
The other perfect example of that is a drug called Avastin, which was recently approved for colon cancer and there are large studies now looking at it for lung cancer. It is an antiangiogenic drug, so it blocks off blood supplies to tumors. Tumors need blood vessels to nutrients and oxygen and grow.
What's the future of lung cancer treatment?
It's very exciting to see that all the work that these scientists have done over the past three decades, to find out what a cancer cell is and what makes it tick, is finally starting to pay off in terms of developing new drugs.
I think where everybody is hoping to go in the future and I think the future's right around the corner is that they will be able to take someone's tumor and study it under the microscope and figure out which of these targeted therapies may be most important. For example, someone's tumor contains a lot of blood vessels, their treatment might involve an antiangiogenic drug, such as Avastin. If they find out that it needs a lot of growth factors to live, they may give a drug that inhibits growth factors, such as Iressa.
One interesting thing that we are learning is that lung cancer seems to behave differently in men than in women. Some nonsmokers can come down with lung cancer and those tend to be women. And some of these new drugs, like Iressa, tend to work better in women. So there's a lot of interest now in exploring gender differences and lung cancer.
There is no screening test for lung cancer, so what should people be aware of?
A cough that doesn't go away should certainly be brought to their doctor's attention. If the cough doesn't go away, the doctor and patient should really be thinking about a chest X-ray, because we see a lot of nonsmoking women, for example, who get diagnosed very late because their doctor never pursued a cough.
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