The primary treatment for non-small cell lung cancer (NSCLC) usually involves surgery, radiation, and chemotherapy. The following is a review of the various types of treatment currently in use, a brief overview of general side effects, and some new therapeutic options being studied that may become available in the future. [For more in-depth information about side effects, see the Managing Symptoms & Side Effects.]

NSCLC treatment is a combination of art and science. It is continually evolving. There is no treatment that has been proven effective for everyone all of the time. This is because lung cancer varies from person to person. As you have read, there are a number of different types of NSCLC. The tumors can also be located in different areas of the lungs. Some people have tumors that are only in the lung(s) at the time of detection, but most tumors will have already spread to the lymph nodes or other parts of the body by the time NSCLC is diagnosed. In addition, while some tumor cells are sensitive to a particular type of treatment, others are not.

The recommendations from your oncology team and the final decisions you make will depend on the stage of your disease, your age, your general health, and the potential side effects. Remember, there is no one treatment for NSCLC. Your treatment will be as individual as you are.

Surgery

There are general surgeons that perform all types of surgery, but not every surgeon has received specialized training beyond that of general surgery. Thoracic surgeons have received extensive specialized training in cardiac (heart) and thoracic (lung) surgery. They tend to be considered the most expert surgeons for lung cancer.

It is important to be comfortable with the skill and experience of the surgeon. In general, the more times a surgeon performs a specific type of surgery, the better skilled he or she is. Do not hesitate to ask your surgeon how many lung cancer surgeries he or she does each year. Because many thoracic surgeons also do heart surgery, you will want to seek out a thoracic surgeon who specializes in lung surgery. If there is no thoracic surgeon available, find a general surgeon who performs the most lung cancer surgery in your area, or get a referral from your diagnosing physician to a nearby cancer center (call 1-800-4CANCER for the locations of the nearest center).

Surgical resection is frequently used when cancer has not spread to other tissues in the chest or elsewhere in the body. If your surgeon and the other oncology professionals on your health care team believe that there is a good chance that all the visible cancer can be surgically removed (resected), surgery will most likely be recommended. Surgery may be the first type of treatment used, or it may be used after you have had chemotherapy and/or radiation, which is given to shrink the tumor(s) before surgery.

When lung cancer is staged and treated with surgery, the surgeon will examine and remove several lymph nodes to check them for cancer. As with other types of cancer, checking the lymph nodes for signs of cancer spread is essential to accurately stage the cancer and decide the best treatment. If you are having surgery, discuss the examination and removal of lymph nodes with your surgeon. [See Staging Lung Cancer.]

Because it is so important to your overall health status, current smokers should stop smoking prior to surgery. Smoking increases the chances of having problems both with the surgery and during the recovery.

The 3 types of surgery used in the treatment of lung cancer are:

• Lobectomy, in which an entire section (lobe) of the lung is removed
• Pneumonectomy, in which the entire lung is removed
• Wedge or segmental resection, in which a small part of the lung is removed

Surgery is not generally used as first-line therapy if the lung cancer has:

• Spread to the other lung
• Spread from the lung into other structures in the chest, such as the heart
• Made it difficult to breathe
• Spread to the lymph nodes in the neck or to other organs, such as the liver, adrenal glands, or brain
• Developed in a part of the lung that makes removal impossible
• Been diagnosed as small cell lung cancer

Surgery is not recommended if there are other health-related problems that would make surgery risky. These may include heart and vascular problems, diabetes, and certain other chronic conditions.

Breathing tests (pulmonary function tests) are usually done to help determine if your lungs will be strong enough during and after the surgery. You may have other tests to assess your ability to undergo surgery, such as a quantitative ventilation/perfusion scan to determine how well the lung is functioning in the parts of the lung that are to be removed.

Sometimes, medications such as bronchodilators, like those used by people who have asthma, will help improve breathing capacity so that surgery can be done. These drugs may improve lung function whether surgery is ultimately performed or not. Some centers or surgeons prepare their patients for surgery by recommending participation in a pulmonary rehabilitation program both before and after surgery. This is especially important if you do not have a regular exercise program.

Side Effects From Surgery

Surgery causes a number of side effects, some of which may disappear within days or weeks. Others may last longer periods of time. The side effects you experience are often dependent on the type of surgery you have.

The most common postoperative side effects can be nausea and vomiting. There are effective medications to prevent or control nausea after surgery that include, among others, ondansetron (Zofran®), granisetron (Kytril®) and dolasetron (Anzemet®). Ask your surgeon if such a medication might be helpful for you.

Incision pain may be another expected side effect immediately after surgery, and patients are provided with effective pain medications. Many people who have had lung surgery complain of lasting pain at the incision site, which is sometimes difficult to eliminate. Women may have an especially difficult time as the incision line is often at the brassiere line. Many women find an alternative to snug clothing to avoid irritating the incision site and causing pain and discomfort.

Another potential side effect of surgery is the stress on the body from the anesthesia and other medications. These stressors tend to reduce the ability of the immune system to ward off infection. It is important to take particular care not to be exposed to people with bad colds or other communicable diseases until you recover fully.

Radiation

Many people with NSCLC will need radiation therapy at some time during their illness, either as part of curative treatment or as a means of providing symptom relief (palliation), when a cure is not possible. Cancer specialists, called radiation oncologists, provide this specialized treatment.

The amount of radiation used against lung cancer varies, based on the size and location of the tumor and the sensitivity of the normal tissue surrounding the tumor. The timing and dosing of radiation (called fractionation) is the subject of study in clinical trials in treating NSCLC. Radiation therapy can be used either alone or in combination with surgery or chemotherapy. It is sometimes used before surgery to shrink a tumor. After surgery, radiation may be used to destroy any cancer cells that may remain.

Side Effects of Radiation

Although the purpose of radiation is to destroy cancer cells, it can also injure normal cells. This can cause side effects from radiation depending on the dose and the size of the area being treated. New technology can significantly reduce the size of the area being treated. Clinical trials that administer radiation more frequently (2 or 3 times a day versus once a day) are evaluating whether this approach provides a better outcome in lung cancer treatment.

Chemotherapy

Chemotherapy drugs are usually given through a vein (intravenously) or taken by mouth and travel throughout the body via the bloodstream (systemically). Chemotherapy drugs destroy cells that are dividing rapidly, which includes cancer cells. They interfere with the cell-division cycle so that cells cannot divide, or are damaged and cannot repair themselves. Chemotherapy drugs also affect rapidly dividing healthy cells in the body, such as blood cells, skin and hair cells, and the cells lining the mouth and intestines.

Chemotherapy treatments are tailored to meet the needs of each person. You and your doctor will develop a chemotherapy treatment plan by considering such things as the type of lung cancer you have, how widespread it is, the potential side effects, your general state of health, and your personal goals related to cancer therapy.

Chemotherapy can be used to:

• Shrink tumors
• Slow cancer’s growth
• Keep the cancer from spreading
• Relieve disease-related symptoms
• Prolong survival

Even if chemotherapy does not cure the disease, studies have shown that it can help people with NSCLC live longer and more comfortably.

Currently Used Chemotherapy Agents

There are a variety of drugs used to treat NSCLC. Sometimes a patient will receive one chemotherapy agent alone or one combined with another type of treatment like radiotherapy.

You may respond better to some drugs than to others, so your physician may try different chemotherapy drugs either alone or in varying combinations to achieve the best results with the fewest side effects. Eventually, the cancer cells that may remain in a tumor may become resistant to a chemotherapy agent or agents, so another type of drug or combination of drugs may then need to be used. Some chemotherapy drugs have more potential side effects than others. It is important when deciding between different treatment options to consider how effective the treatment might be as well as the potential side effects along with your goals of therapy.

Discuss the chemotherapy drugs you will be taking with your physician to gain a complete understanding of the goals of the therapy and potential side effects. Remember, however, that your experience with each drug will be unique. You may experience just a few, or none of the side effects that are associated with a drug. Regardless, your choice of chemotherapy should take into account the potential side effects, whether or not you feel they can be controlled or tolerated.

According to the National Comprehensive Cancer Network’s® (NCCN) Lung Cancer: Treatment Guidelines for Patients, Version 1/December 2001, the following are drug combinations most frequently used for:

Initial first-line chemotherapy for NSCLC:

• Gemcitabine (Gemzar®) + cisplatin (Platinol®)
• Vinorelbine (Navelbine®) + cisplatin (Platinol®)
• Gemcitabine (Gemzar®) + carboplatin (Paraplatin®)
• Paclitaxel (Taxol®) + carboplatin (Paraplatin®)
• Docetaxel (Taxotere®) + cisplatin (Platinol®)

Commonly used second-line chemotherapy agents for recurrent NSCLC (used if the cancer continues to grow during or after initial chemotherapy):

• docetaxel (Taxotere®)
• gemcitabine (Gemzar®) + vinorelbine (Navelbine®)

Treatment of NSCLC by Stage

The stage of a person’s cancer is the chief determinant of his or her treatment plan. Other factors include general health and any medical conditions, such as heart or circulatory disease, diabetes, or other chronic conditions. Another important factor is an individual’s needs or wishes related to potential side effects and their management. Your oncologist will make recommendations, and you and your family will make decisions about your treatment. It is often useful to meet with the specialists (thoracic surgeon, medical oncologist, and radiation oncologist) involved in your care prior to starting treatment to learn about the available options for treatment. Often, a multidisciplinary clinic is available in a nearby cancer center that has all the lung cancer specialists together in one program.

As stated before, there is not one standard treatment currently used by everyone in the medical community to treat every type and every stage of NSCLC. The following is a review of the types of treatments used for the various stages of NSCLC. Keep in mind that these are just general descriptions of the usual approaches to treatment. There are many variations of existing options and many new treatments emerging that provide a variety of treatment options.

Stage 0

Definition
Stage 0 non-small cell lung cancer (also known as carcinoma in situ) is lung cancer that is found only in the layer of cells lining the air passages. Unfortunately, very few people are diagnosed at stage 0. Stage 0 lung cancer is usually discovered by a technique called “sputum cytology.” Most people who are diagnosed with stage 0 are participating in a screening trial or they sought out a special screening test like a spiral CT scan because they were concerned they were at risk.

Surgery
If the tumor’s location can be detected, minimally invasive surgery may be used at this stage to locally remove the tumor and preserve lung function.

Chemotherapy
Chemotherapy is not indicated at this time for stage 0 non-small cell lung cancer.

Photodynamic Therapy
Photodynamic therapy (also called PDT, photoradiation therapy, phototherapy, or photochemotherapy) has been approved by the FDA for treatment of some early stage non-small cell lung cancer (microinvasive disease) when surgery and radiation therapy cannot be used.

In PDT, a photosensitizing drug is injected into the vein. After a period of time, the drug is absorbed by all the cells, then rapidly leaves most normal cells but remains in cancer cells for a longer period of time. The treated cancer cells are then exposed to light from a laser that activates the photosensitizing drug. The photosensitizing drug in the treated cells absorbs the light, producing an active form of oxygen that destroys surrounding cancer cells. Light exposure must be timed carefully so that it occurs when most of the photosensitizing drug has left healthy cells but is still present in the cancerous cells.

Radiation Therapy
Radiation therapy might be recommended for patients at this stage who are unable to undergo surgery for other health reasons.

Stage IA and IB

Definition
In stage IA NSCLC, the cancer is smaller than 3 centimeters (slightly less than 1¼ inches), has not spread to the membranes that surround the lungs, and does not affect the main branches of the bronchi. In addition, the cancer has not spread to the lymph nodes or any other distant organ.

Stage IB NSCLC is defined by a tumor that is larger than 3 centimeters but has not spread to the lymph nodes or a distant site.

Surgery
Surgery is the treatment of choice for patients with stage I NSCLC. Patients diagnosed with stage IA or IB are usually treated with a type of surgery called resection. The current standard treatment is to remove a whole section, or lobe (lobectomy) from the lung during an exploratory surgery. Lobectomies are considered to be superior to a wedge resection that only removes a small portion of a lobe. Removal of an entire lung is called a pneumonectomy.

A pneumonectomy might be done if tumors are found in more than one lobe or one side of the chest. When lung surgery is performed, a complete examination of the lymph nodes in the chest cavity is done. Thoracic surgeons are trained to do these procedures and if you have a choice, you should try to find a board-certified thoracic surgeon.

Additional Therapy
If you are diagnosed with stage IA or IB NSCLC, the standard of care is surgery alone unless the surgeon is concerned that some cancer cells may have been left behind. You should meet with a medical oncologist to discuss the possibility of chemotherapy in addition to surgery. Clinical trials are underway to determine the effectiveness of adding these therapies to surgery for stage IB patients. Clinical trials are also investigating whether or not the use of chemotherapy with these types of patients increases survival time.

Stage IIA and IIB

Definition
In stage IIA NSCLC, the tumor is no larger than 3 centimeters, has not spread to the membranes that surround the lungs, and does not affect the main branches of the bronchi. However, the tumor has spread to the lymph nodes within the cancerous lung but not to any distant sites.

Stage IIB NSCLC is diagnosed when the cancer is either larger than 3 centimeters and has spread to the membranes that surround the lung and/or the lymph nodes within the same cancerous lung, or spread to the chest wall, the diaphragm, the membranes that surround the space between the lungs, or the membranes that surround the sac of the heart without involvement of lymph nodes or distant organs.

Surgery
Surgery is also the treatment of choice for patients with stage II NSCLC. The current standard of treatment for stage IIA and IIB disease is surgical treatment such as a lobectomy, bilobectomy (removal of more than one lobe), or pneumonectomy if the patient can medically tolerate surgery.

Chemotherapy
While neoadjuvant (before surgery) and adjuvant (after surgery) chemotherapy are not standard treatments for stage IIA or IIB NSCLC, clinical trials are under way to see if these types of treatments increase survival time or help provide a cure. If you are diagnosed with stage IIA or IIB NSCLC, it is recommended that you meet with both a medical oncologist and a radiation oncologist to discuss possible clinical trials for your stage of disease.

Radiation
Some radiation oncologists recommend radiation after surgery for stage IIA or IIB disease. Radiation is used after surgery in an attempt to destroy any remaining cancer cells. The radiation is targeted at or around the area where the tumor(s) was located. Controversy exists around the effectiveness of radiation in stage II NSCLC. You should talk with your radiation oncologist about the risks and benefits of radiation for your stage of disease.

Stage IIIA

Definition
Stage IIIA NSCLC is confined to the lung itself and the lymph nodes around the windpipe or in the mediastinum (place behind the chest bone and in front of the heart) on the same side as the cancerous lung. The standard treatment for patients with stage IIIA NSCLC will vary depending on the extent of lymph node involvement.

Surgery
Surgery without chemotherapy may be possible in some cases of stage IIIA NSCLC. For patients with minimal lymph node involvement, the role of surgery is being investigated in clinical trials. The more common approach when mediastinal lymph nodes are involved, however, is to give chemotherapy prior to surgery (neoadjuvant chemotherapy) or radiotherapy to reduce the size of the tumor or tumors. This approach has been shown to be successful in a number of clinical trials involving small numbers of patients.

Chemotherapy
People diagnosed with stage IIIA NSCLC may be considered for induction (more aggressive) chemotherapy and/or radiotherapy plus surgery. All of these options are being studied in clinical trials.

Radiation
Radiation is sometimes used in the treatment of stage IIIA NSCLC to help reduce the size of the tumor(s). Radiation combined with chemotherapy may be used instead of surgery to eliminate the tumor and is probably the most common form of therapy at this stage.

Stage IIIB

Definition
Stage IIIB NSCLC can be a tumor of any size that may involve the bronchus, trachea, esophagus, backbone, or the fluid in the space surrounding the lung and, most importantly, has spread to the lymph nodes near the collarbone on either side and/or the lymph nodes within the lung or mediastinal lymph nodes on the side that is opposite the cancerous lung.

Surgery
Stage IIIB NSCLC has usually invaded surrounding organs, and possibly the lymph nodes outside the chest. Therefore, your pretreatment work-up will focus on whether or not complete surgical removal of the tumor is possible or whether the cancer has already spread to the brain or bone. Whenever possible, your surgeon will try to remove the tumor(s). However, patients with stage IIIB NSCLC do not generally benefit from surgery and are best managed by initial chemotherapy, chemotherapy plus radiotherapy, or radiation therapy alone.

Chemotherapy
Chemotherapy should be used in combination with radiotherapy to treat stage IIIB NSCLC. Numerous clinical trials using a number of new drugs with or without older drugs can help to control stage IIIB NSCLC. Chemotherapy treatments at this stage have been proven effective in controlling and/or slowing the growth of the tumor(s).

People with stage IIIB lung cancer with pleural effusion (leakage of fluid between the lung and chest wall) should receive chemotherapy alone. If no pleural effusion is present, radiation is used in addition to chemotherapy.

Radiation
Radiation therapy is often used in the treatment for stage IIIB NSCLC. The aim is to eliminate the tumor or at least to reduce its size.

Stage IV

Definition
Stage IV NSCLC is the most advanced form of lung cancer because the cancer has spread from the lungs to distant parts of the body such as the liver, brain, or bone. At this stage, chemotherapy, usually a combination of different drugs, is the most commonly recommended form of treatment.

Surgery
Surgery is not usually an option for people diagnosed with stage IV NSCLC unless there is only one metastatic tumor in a distant organ or in the opposite lung. Although surgery at this stage is unlikely to be curative, it can be utilized to relieve symptoms or delay the onset of symptoms.

Chemotherapy
Doctors often recommend palliative (versus curative) chemotherapy for patients with stage IV disease who are otherwise doing well. The main goal of therapy at this stage is often symptom relief, if needed, and increased survival time. Some people with stage IV disease who receive chemotherapy live beyond what is statistically expected. Just as with stage IIIB disease, some people experience complete remission, that is, the disappearance of visible tumors. Other patients can be maintained on a specific treatment for a period of time to keep existing tumors under control.

Radiation
Radiation may be used to relieve symptoms and improve quality of life by reducing the size of the tumor and its effect on surrounding organs.

Photodynamic Therapy (PDT)
PDT may be used for palliation in late-stage lung cancer as a treatment for bronchial obstruction. For example, if a tumor is growing on the main bronchi making it difficult for the patient to breathe, use of PDT could help open the airways by reducing the size of the tumor.

Recurrent Non-Small Cell Lung Cancer

After the initial treatment for lung cancer is completed, it is recommended that you have follow-up tests and exams (physical exam, chest x-ray, chest CT scan). Lung cancer can recur in or near the lungs (local recurrence) or in a distant organ (distant metastasis).

The following treatments may be useful when the tumor has recurred:

Treatment of Local-Regional Recurrence

• Laser and/or other surgical removal
• Brachytherapy (internal radiation)
• Photodynamic therapy (PDT)
• External beam radiation

Treatment of Distant Metastatic Recurrence

• External beam radiation to relieve symptoms
• Bone surgery to prevent or repair fractures
• Surgical removal (if only one tumor in a distant site)

Chemotherapy for Recurrent NSCLC

Chemotherapy may be a reasonable treatment option for recurrent non-small cell lung cancer if you are in relatively good health and can tolerate some of the potential side effects of the treatment. If you choose not to take chemotherapy, supportive care (or treatment that helps relieve symptoms but does not affect the growth of the cancer) may be recommended.

Second-line chemotherapy drugs may be used when tumors continue to grow during or after first-line chemotherapy. At this time, only docetaxel (Taxotere®) is FDA-approved for the treatment of recurrent NSCLC, and clinical trials are investigating whether new treatments compared to a standard treatment may be an appropriate option for patients who do not respond well to first-line chemotherapy treatment. Many patients with recurrent NSCLC are eligible for and often consider clinical trials as a valuable treatment option.

National Cancer Institute (NCI) Recommended Standard Treatment Options for Recurrent NSCLC:

Palliative radiation therapy to relieve symptoms

Chemotherapy alone. For patients who have not received prior chemotherapy, the following regimens are associated with similar survival outcomes:

• Vinorelbine (Navelbine®) + cisplatin (Platinol®)
• Paclitaxel (Taxol®) + cisplatin (Platinol®)
• Gemcitabine (Gemzar®) + cisplatin (Platinol®)
• Paclitaxel (Taxol®) + carboplatin (Paraplatin®)
• Docetaxel (Taxotere®) + cisplatin (Platinol®)
• Vinblastine (Velban®) + mitomycin (Mutamycin®) + cisplatin (Platinol®)*

  *Although listed in the NCI Guidelines, the regimen of cisplatin + vinblastine + mitomycin is rarely used in the United States because other regimens have been proven to be more effective in clinical trials.

Surgical resection of isolated brain metastases (in highly select patients)

Laser therapy or interstitial radiation therapy for endobronchial lesions

Stereotactic radiosurgery (in highly select patients)

This section summarizes the latest information related to the treatment of NSCLC. New treatments are constantly evolving so it is important to keep up on the latest findings from research from your physician, the National Cancer Institute, and through programs such as Frankly Speaking About Lung Cancer.

For More Information:

• National Cancer Institute, 1-800-4CANCER.
• National Comprehensive Cancer Network (NCCN). Lung Cancer: Treatment Guidelines For Patients. 888-909-NCCN (6226).
• The American Cancer Society, 1-800-ACS-2345.