Progress in the Treatment of Lung Cancer

We have entered a new and hopeful era in the treatment of lung cancer.

Each year, more than 226,000 Americans are diagnosed with lung cancer. Cigarette smoking is the primary risk factor for lung cancer, and is the cause of 85 percent to 90 percent of lung cancers. Yet some people who have never smoked still get the disease.

In recent years, there have been some exciting developments in lung cancer treatment. Doctors can now identify specific types of lung cancer cells and prescribe treatments designed to target these cancer cells. This advance has made lung cancer treatment safer and more effective.

Screening for Lung Cancer?

Most lung cancers are first diagnosed based on symptoms. Symptoms of lung cancer are not very specific and generally reflect damage to the lungs’ ability to function normally. The most common symptoms are a worsening cough that will not go away, and chest discomfort. Other symptoms include shortness of breath, spitting up small amounts of blood, unexplained weight loss, loss of appetite, and a general fatigue.

Unlike mammography for breast cancer or colonoscopy for colon cancer, a widely accepted screening tool for early-stage lung cancer was not available until recently. Regular chest X-rays are not reliable enough to find lung tumors in their earliest stages, when many doctors believe the tumors are at their smallest and most curable.

Recent guidelines from the American Society of Clinical Oncology suggests annual screening with low-dose computed tomography (LDCT) for smokers and former smokers, ages 55 to 74, who have smoked for 30 pack-years or more and either continue to smoke or have quit within the past 15 years. At this time, yearly screening with LDCT is recommended for high-risk individuals after careful discussion with their physicians.

Diagnosing Lung Cancer

If lung cancer is suspected, a small piece of tissue from the lung must be examined under a microscope to look for cancer cells. Called a biopsy, this procedure can be performed in different ways. In some cases, the doctor passes a needle through the skin into the lungs to remove a small piece of tissue; this procedure is often called a needle biopsy.

In other cases, a biopsy may be done during a bronchoscopy. To perform a bronchoscopy, the doctor inserts a small tube through the mouth or nose and into the lungs. The tube, which has a light on the end, allows the doctor to see inside the lungs and to remove a small tissue sample.

When a person is diagnosed with lung cancer, looking at biopsied cells under the microscope also helps doctors determine the type of lung cancer. It is important to know the specific type because this information helps doctors recommend the best treatment.

Types of Lung Cancer

There are two major types of lung cancer, non-small cell lung cancer and small cell lung cancer.

Non-small cell lung cancer accounts for about 85 percent of lung cancers. Among them are these types of tumors:

• Adenocarcinoma, which is the most common form of lung cancer in the United States among both men and women.
• Squamous cell carcinoma (which is also called epidermoid carcinoma) forms in the lining of the bronchial tubes.
• Large cell carcinoma refers to non-small cell lung cancers that are neither adenocarcinomas nor epidermoid cancers.

Small cell lung cancer accounts for the remaining 15 percent of lung cancers in the United States. Small cell lung cancer results from smoking even more so than non-small cell lung cancer, and grows more rapidly and spreads to other parts of the body earlier than non-small cell lung cancer. It is also more responsive to chemotherapy.

Stages of Lung Cancer

Staging lung cancer is based on whether the cancer is local or has spread from the lungs to the lymph nodes or other organs.

Non-Small Cell Lung Cancer Stage I: The cancer is located only in the lungs and has not spread to any lymph nodes.
Stage II: The cancer is in the lung and nearby lymph nodes.
Stage III: Cancer is found in the lung and in the lymph nodes in the middle of the chest; also described as locally advanced disease.
Stage III has two subtypes:

• If the cancer has spread only to lymph nodes on the same side of the chest where the cancer started, it is called stage IIIA.
• If the cancer has spread to the lymph nodes on the opposite side of the chest, or above the collar bone, it is called stage IIIB.

Stage IV: This is the most advanced stage of lung cancer, and is also described as advanced disease. This is when the cancer has spread to both lungs, to fluid in the area around the lungs, or to another part of the body, such as the liver or other organs.

Because the lungs are large, tumors can grow in them for a long time before they are found. Even when symptoms—such as coughing and fatigue—do occur, people think they are due to other causes. For this reason, early-stage lung cancer (stages I and II) is difficult to detect. Most people with lung cancer are diagnosed at stages III and IV.

Stages of Small Cell Lung Cancer Limited stage: In this stage, cancer is found on one side of the chest, involving just one part of the lung and nearby lymph nodes.
Extensive stage: In this stage, cancer has spread to other regions of the chest or other parts of the body.

Treatment Options for Lung Cancer

Surgery, radiation, chemotherapy, and targeted treatments—alone or in combination—are used to treat lung cancer. Each of these types of treatments may cause different side effects.

Non-Small Cell Lung Cancer Surgery Most stage I and stage II non-small cell lung cancers are treated with surgery to remove the tumor. For this procedure, a surgeon removes the lobe, or section, of the lung containing the tumor.

Some surgeons use video-assisted thoracoscopic surgery (VATS). For this procedure, the surgeon makes a small incision, or cut, in the chest and inserts a tube called a thoracoscope. The thoracoscope has a light and a tiny camera connected to a video monitor so that the surgeon can see inside the chest. A lung lobe can then be removed through the scope, without making a large incision in the chest.

Chemotherapy and Radiation For people with non-small cell lung cancer tumors that can be surgically removed, evidence suggests that chemotherapy after surgery, known as “adjuvant chemotherapy,” may help prevent the cancer from returning. This is particularly true for patients with stage II and IIIA disease. Questions remain about whether adjuvant chemotherapy applies to other patients and how much they benefit.

For people with stage III lung cancer that cannot be removed surgically, doctors typically recommend chemotherapy in combination with definitive (high-dose) radiation treatments.

In stage IV lung cancer, chemotherapy is typically the main treatment. In stage IV patients, radiation is used only for palliation of symptoms.

The chemotherapy treatment plan for lung cancer often consists of a combination of drugs. Among the drugs most commonly used are cisplatin (Platinol) or carboplatin (Paraplatin) plus docetaxel (Taxotere), gemcitabine (Gemzar), paclitaxel (Taxol and others), vinorelbine (Navelbine and others), or pemetrexed (Alimta).

There are times when these treatments may not work. Or, after these drugs work for a while, the lung cancer may come back. In such cases, doctors often prescribe a second course of drug treatment referred to as second-line chemotherapy.

Recently, the concept of maintenance chemotherapy has been tested in clinical trials, either as a switch to another drug before the cancer progresses; or to continue one of the drugs used initially for a longer period of time. Both of these strategies have shown advantages in selected patients.

Small Cell Lung Cancer

Chemotherapy and Radiation Therapy For people with small cell lung cancer, regardless of stage, chemotherapy is an essential part of treatment. Radiation treatment may be used as well depending on the stage of the lung cancer.

For people with limited-stage small cell lung cancer, combination chemotherapy plus radiation therapy given at the same time is the recommended treatment. The most commonly used initial chemotherapy regimen is etoposide plus cisplatin.

For people with extensive-stage small cell lung cancer, chemotherapy alone using the etoposide plus cisplatin regimen is the standard treatment. However, another regimen that may be used is carboplatin plus irinotecan (Camptosar).

Radiation therapy of the brain may be used before or after chemotherapy for some people whose cancer has spread to the brain.

Preventive Radiation Therapy to the Brain In more than one-half of the people with small cell lung cancer, the cancer also spreads to the brain. For people whose lung cancer has responded to chemotherapy, doctors may prescribe radiation therapy to the brain to help prevent the cancer from spreading to the brain. This can benefit the patient with both limited-stage and extensive-stage small cell lung cancers.

Surgery A very small percentage of people who have limited-stage small cell lung cancer and no lymph node tumors may benefit from surgery, after which adjuvant chemotherapy is given.

Chemotherapy Before Other Treatments Receiving chemotherapy before radiation or surgery may help people with lung cancer by shrinking the tumor enough to make it easier to remove with surgery, increasing the effectiveness of radiation and destroying hidden cancer cells at the earliest possible time.

If a tumor doesn’t shrink with chemotherapy, the medication can be stopped right away, allowing the doctor to try a different treatment. In addition, research shows that people with lung cancer are much more able to cope with the side effects of chemotherapy when given before surgery.

Sometimes, a short trial period of treatment with the drug shrinks the tumor before surgery. If that is the case, then continued treatment with the same drug after surgery is more likely to benefit the patient. Because many lung cancer specialists around the world are giving chemotherapy to their patients before surgery, patients should discuss it with their doctor.

Targeted Treatments

One of the most exciting developments in lung cancer medicine is the introduction of targeted treatments. Unlike chemotherapy drugs, which cannot tell the difference between normal cells and cancer cells, targeted therapies are designed specifically to attack cancer cells by attaching to or blocking targets that appear on the surfaces of those cells. People who have advanced lung cancer with certain molecular biomarkers may receive treatment with a targeted drug alone or in combination with chemotherapy. These treatments for lung cancer include:

BMS-936558 Initial research on using the body’s immune system to target cancer cells may hold promise in advanced non-small cell lung cancer that no longer responds to treatment. In two early clinical trials, the drug BMS-936558 was able to significantly shrink tumors and keep tumor progression in check for a prolonged duration in patients with advanced lung cancer. The drug, an antibody, blocks the PD-1 pathway, which is a key pathway used by tumors to escape attack by the body’s immune system. Phase III clinical trials are under way in previously treated non-small cell lung cancer patients with squamous or non-squamous types of lung cancer.

Bevacizumab (Avastin) Just like normal tissues, tumors need a blood supply to survive. Blood vessels grow in several ways. One way is through the presence of a substance called vascular endothelial growth factor (VEGF). This substance stimulates blood vessels to penetrate tumors and supply oxygen, minerals, and other nutrients to feed the tumor. When tumors spread throughout the body, they release VEGF to create new blood vessels.

Bevacizumab works by stopping VEGF from stimulating the growth of new blood vessels. (Because normal tissues have an established blood supply, they are not affected by the drug.) When combined with chemotherapy, bevacizumab has been shown to improve survival in people with certain types of non-small cell lung cancer, such as adenocarcinoma and large cell carcinoma.

Crizotinib (Xalkori) Crizotinib is a newly available treatment that has shown benefits for people with advanced non–small cell lung cancer who have the ALK biomarker. Mutations in the way cells program ALK result in changes to the way it functions, leading to increased tumor cell growth. Crizotinib works by blocking ALK and stopping the growth of the tumor.

Erlotinib (Tarceva) A targeted treatment called erlotinib has been shown to benefit some people with non-small cell lung cancer. This drug blocks a specific kind of receptor on the cell surface—EGFR. Receptors such as EGFR act as doorways by allowing substances in that can encourage a cancer cell to grow and spread. Lung tumors with an EGFR mutation are very sensitive and are often treated with erlotinib instead of chemotherapy. For patients who have received chemotherapy, and are in need of additional treatment, erlotinib can be used even without the presence of the mutation.

Q. My breathing has been affected by surgery and first-line chemotherapy. Is that common?

A. When surgery is a part of your treatment for lung cancer, it reduces the size of the lungs and you do not take in as much air. When this happens, pulmonary rehabilitation therapy, which your doctor can prescribe, is the best way to help improve lung function. Shortness of breath also may be due to the underlying lung disease or less frequently a direct effect of chemotherapy. Some drugs can change lung function and cause inflammation. Shortness of breath is something that you should discuss with your doctor and other health care providers to find the source and the best solution.

Q. My mother was diagnosed with stage IV lung cancer and she has developed blood clots in her legs. Is there anything she can do to manage this side effect?

A. Blood clots are a common complication of cancer. Sometimes they are caused by the cancer itself and sometimes by its treatment. Doctors prescribe blood thinners to prevent further clots. If the blood clots caused some damage to the vein, your mother may want to ask her doctor for a referral to a vascular specialist—an expert in the treatment of circulation and blood vessels. Another option for your mother might be to wear elastic stockings to help manage any pain, discomfort, or swelling. For many people, treatment is highly effective, and the symptoms of the blood clots tend to go away over time. Encourage her to speak with her doctor for additional recommendations on managing this side effect.

Q. I have lung cancer in my family—my grandmother and father were smokers. I do not smoke. Is lung cancer hereditary?

A. Like most diseases, lung cancer is not entirely due to environmental causes. We know this because not all smokers develop lung cancer whereas about 20 percent of people who get lung cancer have never smoked. Some of these people may have had other exposures, but there are also underlying genetic causes, not all of them known. Doctors have identified specific genetic mutations that occur more often in people with lung cancer who have never smoked than those with lung cancer who were smokers. For people with a family history of lung cancer, avoiding smoking is important, as is maintaining regular physicals and making sure your health care team is aware of your family history.

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This e-booklet was made possible by an educational grant from Eli Lilly and Company.

The information presented in this publication is provided for your general information only. It is not intended as medical advice and should not be relied upon as a substitute for consultations with qualified health professionals who are aware of your specific situation. We encourage you to take information and questions back to your individual health care provider as a way of creating a dialogue and partnership about your cancer and your treatment.