Lung Cancer

Treatment for Lung Cancer

Surgery, radiation therapy, chemotherapy, and targeted therapy are options for treating lung cancer. Surgery and radiation are considered local therapies, and chemotherapy and targeted therapy are considered systemic treatments because the drugs travel throughout the body via the bloodstream. These four types of treatment are most often used in some combination, an approach called combined-modality or multimodality therapy. A specific treatment plan is selected according to several factors, such as the histologic type of lung cancer, the stage of disease, the location of the tumor and the person’s overall lung function and general health. In addition, recent studies have shown that identifying the presence of specific genetic alterations in the tumor tissue is an important factor in selecting an effective treatment approach.

An overview of the types of treatment that may be used for lung cancer is provided in this article. On the pages that follow, you will find more information on treatment options according to specific stages of disease. Each type of treatment is associated with side effects, but advances in treatment have made it possible to control these effects to help you remain comfortable.

Surgery

Surgery is typically the treatment of choice when the cancer is diagnosed at a very early stage. About one in every three or four non-small cell lung cancers is diagnosed at an early stage, but fewer small cell lung cancers are diagnosed early. In addition to an early stage, other requirements for surgery are that the tumor can be removed entirely and that the person’s health status be adequate to tolerate the surgery. Some tumors are considered to be inoperable because of their location near vital structures and some people are not surgical candidates because of poor general health or lung and/or heart function. Ideally, the decision about whether a lung cancer tumor can be surgically removed should be made by a Board-certified thoracic (chest) surgeon who is experienced with lung cancer surgery. When surgery is appropriate, the surgical removal of the tumor is preferred over any other means of destroying the tumor, such as radiofrequency ablation, cryotherapy or stereotactic radiation.

There are four types of surgery, and the type chosen depends on how much of the lung is affected by cancer (Table 1). Media-stinal lymph nodes and other nearby lymph nodes must be removed or sampled during any of these operations to determine whether they have become involved with cancer. The surgical technique for entering the chest cavity to remove the tumor may be a standard thoracotomy, for which a very large incision is made; an operation done through a small incision in the chest, which preserves muscles and/or nerves in the area; or a video-assisted operation (video-assisted thoracotomy-[VAT]), in which several small incisions are made to allow entry of the equipment to remove the lobe (or segment) of the lung and the ribs do not need to be spread (as in the other surgical approaches). VAT is a newer technique and is associated with shorter hospital stays and fewer complications and may thus be preferred, however, this approach cannot be used when the tumor is large or is in a central location. With any of these operations, you will receive general anesthesia so that you are asleep and not able to feel pain during the surgery. In general, people who have surgery stay in the hospital about 4-7 days.

Table 1. Type of Surgery for Lung Cancer

Radiation Therapy

Radiation therapy is the use of high-energy x-rays to kill cancer cells or keep them from growing. In the past, the outcomes after radiation therapy were not as good as the outcomes after surgery, so radiation therapy was used only for people who had inoperable tumors or were not surgical candidates because of other health reasons. Newer radiation techniques are more effective than previous techniques and are being considered as initial therapy for small tumors in people who are poor surgical candidates.

The type of radiation therapy used most often for small cell and non-small cell lung cancer is external-beam radiation therapy, which is delivered from a machine outside of the body. Stereotactic body radiation therapy (SBRT) is an advanced method of delivering radiation. With SBRT, three-dimensional computer imaging is used to deliver high doses of radiation through many small radiation beams highly focused on precise areas. This technique is used more frequently for small tumors in people in poor medical health. Another advanced radiation technique is intensity-modulated radiation therapy (IMRT); with IMRT, the intensity of the radiation delivered to the chest area is varied and targets the tumor more exactly.

Radiation therapy may be used in several different ways: as primary treatment for early stage lung cancer that is inoperable; as adjuvant therapy (after surgery) or neoadjuvant therapy (before surgery), with or without chemotherapy; and as palliative therapy, to relieve symptoms associated with incurable lung cancer. Radiation therapy may also be used to treat lung cancer that has metastasized to the brain.

A radiation oncologist will have oversight of your radiation therapy. Before you begin actual treatment, your radiation oncologist will meticulously plan your radiation therapy to calculate the appropriate dose and determine the optimum treatment schedule. Treatment schedules vary according to the type and stage of lung cancer and the method of delivering radiation. Standard external-beam radiation therapy is delivered in daily doses, 5 days a week, and may take 6-7 weeks to complete. With SBRT, higher doses of radiation are given in just a few days. Each radiation treatment session typically lasts 30 minutes or less and is painless. Radiation therapy for lung cancer will not make you radioactive.

Chemotherapy

Chemotherapy is the use of strong drugs, also known as cytotoxic drugs, to stop the growth of cancer, either by killing cancer cells or by preventing them from dividing and growing. Chemotherapy is sometimes referred to as conventional chemotherapy to distinguish it from targeted therapy, which also involves the use of drugs that travel throughout the body. Unlike chemotherapy, targeted therapy drugs are directed at properties of the cancer cells that are not present on normal cells.

Chemotherapy is the primary treatment for people with all stages of small cell lung cancer unless a person’s body cannot tolerate the drugs because of other medical conditions. Chemotherapy is also an option for all stages of non-small cell lung cancer except for stage I. When used to treat non-small cell lung cancer, chemotherapy may be given after local therapy, such as surgery, to help prevent the cancer from recurring (growing back). This is known as adjuvant chemotherapy. Chemotherapy may also be given to help shrink the tumor to make it easier to treat with surgery or radiation therapy. This treatment is known as neoadjuvant chemotherapy. Chemotherapy may be given concurrently (at the same time) in combination with radiation. This combination of treatments is often referred to as chemoradiation therapy. Lastly, chemotherapy may be used as maintenance therapy for non-small cell lung cancer, which is treatment given after the end of standard chemotherapy to help delay the progression of cancer.

Many chemotherapy drugs are available for the treatment of both small cell and non-small cell lung cancer, and the choice of specific drugs primarily depends on the histologic type of cancer (Table 2). For example, some drugs have been found to be less effective for squamous cell carcinoma than for the other subtypes of non-small cell lung cancer. The choice also depends on how it is being used (as adjuvant treatment, for advanced disease, or with radiation therapy) and on the risk-benefit profiles of the chemotherapy drugs.

For first-line (initial) chemotherapy, the preference is to use a two-drug regimen, referred to as a doublet, with one of the drugs being a platinum drug (cisplatin or carboplatin); studies have found that adding a third chemotherapy drug does not increase survival. If the cancer does not respond to first-line treatment or if cancer progresses, different chemotherapy drugs may be tried. A single drug is frequently used for second-line or third-line therapy. Two drugs have been approved for use as maintenance therapy. The chemotherapy drug pemetrexed (Alimta) is an option for people with a type of cancer other than squamous cell carcinoma, and targeted therapy with erlotinib (Tarceva) is an option for any type of non-small cell lung cancer.

Chemotherapy is usually given intravenously, or through a vein in your arm; some chemotherapy drugs may be given by mouth. You may be able to receive chemotherapy in your doctor’s office or in an outpatient clinic. It typically takes 30-180 minutes for the chemotherapy to be completely infused. Chemotherapy is given in cycles, which refers to treatment on specific days over a period of time (usually 21 or 28 days). Sometimes there are different chemotherapy schedules that can be used, and you can discuss the choice of schedule with your treatment team. Treatment most often consists of four to six cycles, and each cycle is followed by a rest period, to allow your body to recover from the effects of the drug.

Physical exams and imaging studies are repeated after two and four cycles to determine if the treatment is working and to make a decision about when to stop or change treatment if it is no longer effective.

Table 2. Chemotherapy Drugs Used for Small Cell and Non-Small Cell Lung Cancer

*Approved for use in combination with either cisplatin or carboplatin for non-small cell lung cancer.
Pemetrexed is approved only for non-small cell lung cancers other than squamous cell carcinoma.

†Used most often along or with a platinum drug for small cell lung cancer.

Targeted Therapy

Researchers have learned about the cell pathways that can lead to many types of cancers and have also learned how to develop drugs that block those pathways. These drugs are known as targeted drugs (or agents), and treatment with these drugs is known as targeted therapy. Targeted therapy drugs block the signals that proteins and other molecules send along signaling pathways, systems in the body that direct basic cell functions, such as cell growth, cell division (proliferation), and cell death.

Effective targeted therapy depends on two factors: identifying targets that play an important role in the growth and survival of cancer cells and developing agents that can attack those targets. The emerging use of testing for genetic alterations in tumor tissue is helping to advance the use of targeted therapy. Targeted therapy, in combination with chemotherapy, is currently approved for advanced non-small cell lung cancers. As the results of ongoing research are reported, the hope is that the use of targeted therapy can expand to earlier stage disease, which can help extend survival for more people. Targeted therapy has not yet been found to be of benefit for the treatment of small cell lung cancer.

One signaling pathway involved in the development of many different kinds of cancer, including non-small cell lung cancer, is directed by the epidermal growth factor receptor (EGFR) protein, which is made by the EGFR gene. Mutations (alterations) in the EGFR gene activate the EGFR protein, which, in turn, triggers a complex process that leads to increased growth and division of cancer cells and development of metastases. Targeted therapy drugs have been developed to block the activity of EGFR, and these drugs are known as EGFR inhibitors. Two EGFR inhibitors — erlotinib and gefitinib — have been shown to be effective in clinical trials and are approved by the US Food and Drug Administration (FDA) for some types of advanced non-small cell lung cancer (Table 3). It is important to test the tumor tissue for genetic mutations because response to an EGFR inhibitor is more likely if the tumor tests positively for the EGFR mutation and is less likely if the tumor tests positively for the KRAS mutation or the EML4-ALK fusion gene.

Another targeted agent used for non-small cell lung cancer targets a different pathway, a pathway directed by the vascular endothelial growth factor (VEGF). The VEGF pathway is involved in the formation of new blood vessels, and the targeted agent interferes with signals between VEGF and its receptors. As a result, no new blood vessels are formed. Without vessels to bring blood to the tumor, it cannot continue to grow. One VEGF inhibitor, bevacizumab, is approved for use in advanced non-small cell lung cancer (Table 3). VEGF inhibitors are also known as antiangiogenic drugs. Unfortunately, there is no test to determine which people are most likely to benefit from a VEGF inhibitor, and this targeted therapy drug cannot be used for everyone. For example, a VEGF inhibitor is not used for people with squamous cell carcinoma because it may cause excess adverse events and the drug has not been found to be effective for small cell lung cancer.

The newest targeted agent, approved in late August 2011, inhibits the ALK protein (Table 3). This drug, crizotinib (Xalkori) is approved for treatment of adenocarcinomas that test positively for the EML4-ALK fusion gene.

One of the most important problems associated with both chemotherapy and targeted therapy is that cancer cells often become resistant to the drug or drugs, and they becomes less effective over time. Researchers continue to explore ways to overcome resistance.

Table 3. Targeted Therapy Agents Used for Non-Small Cell Lung Cancer

*The use of gefitinib was limited after erlotinib was found to improve survival for the same indications.

Treatment-Related Words You Should Know

Additional Sources of Information

• Lung Cancer Alliance: www.lungcanceralliance.org
    New and Emerging Treatments in Lung Cancer
• National Cancer Institute: www.cancer.gov
    Drugs Approved for Lung Cancer
• National Comprehensive Cancer Network: www.nccn.com
    NCCN Guidelines for Patients: Non-Small Cell Lung Cancer