What`s new in non-small cell lung cancer research and treatment?

Lung cancer research is currently being done in medical centers throughout the world. Progress in prevention, early detection, and treatment based on current research is expected to save many thousands of lives each year.

Prevention

Tobacco

At this time, many researchers believe that prevention offers the greatest opportunity to fight lung cancer. Although decades have passed since the link between smoking and lung cancers was clearly identified, scientists estimate that smoking is still responsible for about 87% of lung cancer deaths. Research is continuing on:

• Ways to help people quit smoking through counseling, nicotine replacement, and other medicines
• Ways to convince young people to never start smoking
• Inherited differences in genes that may make some people much more likely to get lung cancer if they smoke or are exposed to someone else's smoke

Diet, nutrition, and medicines

Although researchers are looking for ways to use vitamins or medicines to prevent lung cancer in people at high risk, so far none have been shown to conclusively reduce risk. Some studies have suggested that a diet high in fruits and vegetables may offer some protection, but more research is needed to confirm this. For now, most researchers think that simply following the American Cancer Society dietary recommendations (such as maintaining a healthy weight and eating at least 5 servings of fruits and vegetables each day) may be the best strategy.

Early detection

As mentioned in the section "Can non-small cell lung cancer be found early?", a large clinical trial called the National Lung Screening Trial (NLST) recently found that spiral CT scanning in people at high risk of lung cancer (due to smoking history) lowered the risk of death from lung cancer, when compared to chest x-rays. This finding has led to the development of screening guidelines for lung cancer.

Another approach uses newer, more sensitive tests to look for cancer cells in sputum samples. Researchers have recently found several changes that often affect the DNA of lung cancer cells. Current studies are looking at new diagnostic tests that specifically recognize these DNA changes to see if this approach is useful in finding lung cancers at an earlier stage.

Diagnosis

Fluorescence bronchoscopy

Also known as autofluorescence bronchoscopy, this technique may help doctors find some lung cancers earlier, when they may be easier to treat. For this test, the doctor inserts a bronchoscope through the mouth or nose and into the lungs. The end of the bronchoscope has a special fluorescent light on it, instead of a normal (white) light.

The fluorescent light causes abnormal areas in the airways to show up in a different color than healthy parts of the airway. Some of these areas might not be visible under white light, so the color difference may help doctors find these areas sooner. Some cancer centers now use this technique to look for early lung cancers, especially if there are no obvious tumors seen with normal bronchoscopy.

Virtual bronchoscopy

This imaging test uses CT scans to create detailed 3-dimensional pictures of the airways in the lungs. The images can be viewed as if the doctor were actually using a bronchoscope.

Virtual bronchoscopy has some possible advantages over standard bronchoscopy. First, it is non-invasive and doesn't require anesthesia. It also helps doctors view some airways that might not be seen with standard bronchoscopy, such as those being blocked by a tumor. But it has some drawbacks as well. For example, it doesn't show color changes in the airways that might indicate a problem. It also doesn't allow a doctor to take samples of suspicious areas like bronchoscopy does. Still, it can be a useful tool in some situations, such as in people who might be too sick to get a standard bronchoscopy.

This test will likely become more available as the technology improves.

Treatment

Chemotherapy

New combinations: Many clinical trials are comparing the effectiveness of newer combinations of chemotherapy drugs. These studies are also providing information about reducing side effects, especially in patients who are older and have other health problems. Doctors are also studying better ways to combine chemotherapy with radiation therapy and other treatments.

Lab tests to help predict if chemo will be helpful: Doctors know that adjuvant chemotherapy after surgery may be more helpful for some people with early (stage I or II) cancers than for others, but figuring out which patients to give it to is not easy. In early studies, newer lab tests that look at patterns of certain genes in the cancer cells have shown promise in telling which people might benefit most. Larger studies of these tests are now trying to confirm their usefulness.

Other lab tests may help predict whether a lung cancer will respond to particular chemo drugs. For example, studies have found that tumors with high levels of the ERCC1 protein are less likely to respond to chemo that includes cisplatin or carboplatin, while tumors with high levels of the RRM1 protein seem less likely to respond to chemo with gemcitabine. Some doctors are now using tests for these markers to help guide the choice of treatment.

Maintenance chemotherapy: For people with advanced lung cancers who can tolerate chemotherapy, combinations of 2 drugs are typically given for about 4 to 6 cycles. Doctors often do not give more chemotherapy unless the cancer starts growing again. But some recent studies have found that with cancers that have not progressed, continuing treatment beyond the 4 to 6 cycles with a single drug – either a chemotherapy drug such as pemetrexed or a targeted drug such as erlotinib – may help some people live longer. This is known as maintenance therapy. A possible downside to this continued treatment is that people may not get a break from having side effects from chemotherapy. Some doctors now recommend maintenance therapy, while others await further research on this topic.

Targeted therapies

Researchers are learning more about the inner workings of lung cancer cells that control their growth and spread. This is being used to develop new targeted therapies. Some of these treatments, such as bevacizumab (Avastin), erlotinib (Tarceva), cetuximab (Erbitux^®), and crizotinib (Xalkori^®) are already being used to treat non-small cell lung cancer. Others are now being tested in clinical trials to see if they can help people with advanced lung cancer live longer or relieve their symptoms.

Some of the other targeted drugs in late stage clinical trials include vadimezan (DMXAA, ASA404), afatinib (BIBW 2992), and motesanib (AMG 706). Some targeted drugs already approved for use against other types of cancer, such as sorafenib (Nexavar) and sunitinib (Sutent), are also being tested for use against NSCLC.

Researchers are also working on lab tests to help predict which patients will benefit from which drugs. Studies have found that some patients do not benefit from certain targeted therapies, whereas others are more likely to have their tumors shrink significantly. For example, a test can find changes in the EGFR gene that make it much more likely that a person's lung cancer will respond to treatment with erlotinib (Tarceva), an EGFR inhibitor. Similar gene tests for other treatments are now being studied. Predicting who might benefit could save some people from trying treatments that are unlikely to work for them and would probably cause unneeded side effects.

Immune treatments

Vaccines: Several types of vaccines for boosting the body's immune response against lung cancer cells are being tested in clinical trials. Unlike vaccines against infections like measles or mumps, these vaccines are designed to help treat, not prevent, lung cancer. One possible advantage of these types of treatments is that they seem to have very limited side effects, so they might be useful in people who can't tolerate other treatments.

Some vaccines are made up of lung cancer cells that have been grown in the lab, or even of cell components, such as parts of proteins commonly found on cancer cells. For example, the MUC1 protein is found on some lung cancer cells. A vaccine called TG4010 causes the immune system to react against that protein. A recent study compared combining the vaccine with chemotherapy to treatment with the same chemotherapy alone in patients with advanced lung cancer. The cancers in group that got the vaccine were more likely to shrink or stop growing than the cancers in the group that just got chemo. More studies are planned to see if the vaccine will actually help patients live longer.

L-BLP25 (Stimuvax) is another vaccine that targets the MUC1 protein. It is made up of a the protein (MUC1) encased in a fat droplet (liposome) to make it more effective. A small study of patients with advanced NSCLC suggested it may improve survival time. Larger studies are being done to try to confirm this.

At this time, vaccines are only available in clinical trials.

Talactoferrin (TLF): This protein is a genetically engineered form of the human protein lactoferrin, which is normally found in body secretions such as breast milk, tears and saliva. In studies, TLF has been shown to stimulate the immune system. It seems to have anti-infective and anti-inflammatory properties, as well as anti-tumor activity. In a recent study of patients with advanced lung cancer whose cancers had grown despite previous chemo, the group that got TLF lived longer than the group that got the placebo (sugar pill). There were few side effects related to treatment. A larger study is planned.