INTRODUCTION

Stage IV non-small cell lung cancer includes cancers that have spread to areas beyond the chest, like the brain (figure 1). Stage IV cancer also includes people who have a fluid collection around the lung (called a malignant pleural effusion) caused by the cancer.

Stage IV non-small cell lung cancer cannot be cured, but treatment can reduce pain, ease breathing, and extend and improve quality of life.

Treatment of stage I to III non-small cell lung cancer is discussed separately. (See "Patient information: Non-small cell lung cancer treatment; stage I to III cancer".) More detailed information about stage IV non-small cell lung cancer is available by subscription. (See "Overview of the treatment of advanced non-small cell lung cancer".)

CHEMOTHERAPY

The most commonly recommended treatment for stage IV non-small cell lung cancer is chemotherapy. Chemotherapy can slow or stop the growth of tumors, which are often spread throughout the body. However, surgery might be an option if the cancer has spread to a single place outside the lung.

Chemotherapy is a treatment given to slow or stop the growth of cancer cells. It is not given every day but instead is given in cycles. A cycle of chemotherapy (which is typically 21 or 28 days) refers to the time it takes to give the treatment and then allow the body to recover from the side effects of the medicines. Your healthcare provider can describe which chemotherapy drugs will be needed. (See "Initial systemic chemotherapy for advanced non-small cell lung cancer".)

Most treatments involve a combination of two chemotherapy drugs (called regimens). Most of the drugs are given into a vein (intravenous, IV).

Four to six cycles of chemotherapy are usually recommended. There is debate about what treatment, if any, should be given after chemotherapy. Talk to your doctor to decide what treatment is right for you.

Side effects — The most serious side effect of chemotherapy is a temporary drop in your blood count. This can increase your risk of developing an infection. Blood counts typically fall 7 to 14 days after the chemotherapy is given. During this time, you should call your doctor or nurse immediately if you develop chills or have a fever (temperature higher than 100.4ºF or 38ºC).

Other possible side effects of chemotherapy include:

• Temporary hair loss
• Numbness in the fingers and toes (called neuropathy)
• Nausea and vomiting
• Skin rash

Treatment for older people and those who are ill — Some people are not healthy enough to have the chemotherapy regimen described above. This might include people who are older or who have another serious illness. In this case, treatment with one chemotherapy medicine (rather than two or three) or a targeted therapy (see 'Targeted therapy' below) is an option. This type of treatment can prolong survival and improve quality of life. The side effects of one chemotherapy medicine are not as severe as when two are used.

TARGETED THERAPY

Targeted therapy is the name for anticancer treatments that were developed to interfere with how a cancer grows and spreads. These treatments work in a different way than standard chemotherapy. There are several types of targeted therapies for lung cancer. The decision about which targeted therapy, if any, to use depends on your particular cancer. Testing can be done to see if your cancer is likely to respond to targeted therapy.

• Erlotinib and geftinib — Erlotinib (Tarceva®) and gefitinib (Iressa®) are targeted chemotherapy medicines that block a specific molecule (epidermal growth factor receptor, or EGFR). These medicines work best in people whose tumors contain a particular abnormality. There is a test for this abnormality, and if the abnormality is found, targeted therapy might be used instead of standard chemotherapy. (See "Targeted agents in the initial systemic treatment of advanced non-small cell lung cancer".)

The most common side effects of erlotinib and geftinib are skin rash and diarrhea.

• Cetuximab — Cetuximab also targets the epidermal growth factor receptor (EGFR). However, cetuximab is usually used in addition to, rather than instead of, standard chemotherapy medicines. Side effects with cetuximab can include skin rash, diarrhea, and low blood counts.
• Bevacizumab — Some people with non-small cell lung cancer have a protein called vascular endothelial growth factor (VEGF). VEGF is involved in the blood supply within a growing cancer, which helps the tumor to grow and spread.

Bevacizumab (Avastin®) is a targeted medicine that blocks the VEGF and interferes with tumor growth. It also enhances the effect of other chemotherapy drugs. It is usually given into a vein (IV) once every three weeks. If bevacizumab is used in combination with chemotherapy, it is usually continued until the cancer begins to grow or spread into new areas.

Bevacizumab is not suitable for everyone, because it can cause serious or even fatal episodes of heavy bleeding in a small percentage of people. People at highest risk of bleeding include those with brain metastases and those who cough up blood or take warfarin (Coumadin).

MANAGEMENT OF METASTASES IN NON-SMALL CELL LUNG CANCER

The brain, the bones, and the area around the lungs (the pleural space) are common places for cancer to spread in people with non-small cell lung cancer. Cancer that has spread to the brain or bones is called metastatic lung cancer, not brain cancer or bone cancer.

Malignant pleural effusion — A pleural effusion is a collection of fluid in the chest that is located in the pleural space, a pocket between the lung and the tissues of the chest wall (figure 1). This space is normally empty, although it can accumulate fluid in people with advanced lung cancer. The fluid pushes against the lung, compressing it and preventing the lung from fully expanding when breathing. Thus, the most common symptom of a pleural effusion is shortness of breath.

In most people with advanced lung cancer, the pleural effusion is caused by the cancer. This is called a malignant pleural effusion. (See "Management of malignant pleural effusions".)

Treatment of the pleural effusion is usually recommended for people who develop shortness of breath. Shortness of breath often worsens as more fluid accumulates.

Fluid drainage — The simplest way to treat a pleural effusion is to insert a small tube (a catheter) into the space around the lung and allow the fluid to drain out. Afterward, the catheter is removed. This is called a thoracentesis. Thoracentesis can usually be done in the office or hospital room using local anesthesia.

If the fluid reaccumulates quickly, meaning that you need another thoracentesis in less than one month, a more aggressive treatment might be recommended. This includes a catheter that is left in place (a tunneled catheter) or using a substance to block the build-up of fluid (called pleurodesis).

• Tunneled catheter — Some people are treated with a catheter that is left in the pleural space and connected to a container. This is called a tunneled catheter. The patient (or a family member) uses a hand pump to drain the fluid once a day or as needed. The catheter is usually inserted during a day surgery procedure. It is left in place for several weeks or months, as long as the fluid continues to drain.

The advantage of a catheter over other treatments is that it allows the patient and their doctors to manage the fluid collection out of the hospital.

• Pleurodesis — Another option for treating a malignant effusion is called chemical pleurodesis. This involves draining the fluid and then applying a substance (usually talcum powder) to fill the pleural space, preventing the fluid from collecting again. This treatment is usually done in the hospital and requires a three- to five-day stay.

Brain metastases — Symptoms of brain metastases can include:

• Headache (often in the morning)
• Weakness
• Trouble thinking clearly
• Seizures (convulsions)

If your doctor is concerned about brain metastasis, he or she will order a magnetic resonance imaging (MRI) study or CT scan. Treatments for brain metastases include radiation therapy and medicines to reduce brain swelling (steroids).

However, people who have one or a small number of metastases in the brain and have no other sites of metastasis are sometimes offered more aggressive treatment. This might include surgery to remove the brain tumor, followed by radiation therapy of the entire brain.

Stereotactic radiosurgery (also called gamma knife treatment) is an alternative to conventional surgery in selected patients. Stereotactic radiosurgery does not actually require surgery but instead uses high doses of radiation in a small area. This treatment is usually used in combination with radiation therapy to the entire brain to slow the regrowth of the cancer.

The intention of radiation therapy for brain metastases is not to cure the cancer. However, radiation therapy can reduce symptoms (headaches, seizures) and improve quality of life.

Short courses of radiation therapy (RT) might also be recommended to treat shortness of breath caused by a blockage of the airway, difficulty swallowing, or spitting up blood.

Bone metastases — Bone metastases can cause bone pain and fractures. There are several options for treating bone metastases: chemotherapy, radiation therapy, and a medicine called a bisphosphonate.

• Chemotherapy can shrink and slow the growth of bone metastases (see 'Chemotherapy' above).
• Radiation therapy can reduce bone pain caused by metastases. This treatment is a good option for people with severe bone pain caused by metastasis in one or a limited number of areas. The treatment usually begins to relieve pain within one week after treatment. The treatment is given in one or a few doses, similar to having an X-ray.
• A medicine called a bisphosphonate might be used to prevent bone-metastasis-related problems, like fractures and bone loss. If you plan to have this treatment, you should have any important dental work done first. There is a risk of a serious problem in the jaw bone related to dental work done after treatment with the high doses of bisphosphonates used to treat bone metastases.

END OF LIFE CARE

Stage IV lung cancer cannot be cured. Deciding when to stop treating the cancer can be difficult and should involve the patient, family, friends, and the healthcare team.

Ending cancer treatment does not mean ending care. Hospice care is frequently recommended when a person is unlikely to live longer than six months. Hospice care involves treatment of all aspects of a patient's and family's needs, including the physical (eg, pain relief), psychological, social, and spiritual aspects of suffering. This care can be given at home or in a nursing home or hospice facility and usually involves multiple care providers, including a doctor, registered nurse, nursing aide, a chaplain or religious leader, a social worker, and volunteers.

These providers work together to meet the patient's and family's needs and significantly reduce their suffering. For more information about hospice, see www.hospicenet.org (also (see "Hospice: Philosophy of care and appropriate utilization").

CLINICAL TRIALS

Progress in treating lung cancer requires that better treatments be identified through clinical trials, which are conducted all over the world. A clinical trial is a carefully controlled way to study the effectiveness of new treatments or new combinations of known therapies. Ask for more information about clinical trials, or read about clinical trials at:

• www.cancer.gov/clinical_trials/learning/
• www.cancer.gov/clinical_trials/
• http://clinicaltrials.gov/

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed every four months on our Web site (www.uptodate.com/patients).

Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.

Patient level information

Patient information: Non-small cell lung cancer treatment; stage I to III cancer

Professional level information

Adjuvant systemic therapy in resectable non-small cell lung cancer
Bronchioloalveolar carcinoma
Cigarette smoking and other risk factors for lung cancer
Diagnosis and staging of non-small cell lung cancer
Initial systemic chemotherapy for advanced non-small cell lung cancer
Investigational approaches for advanced non-small cell lung cancer
Management of malignant pleural effusions
Management of stage I and stage II non-small cell lung cancer
Management of stage III non-small cell lung cancer
Molecular markers in non-small cell lung cancer
Multiple primary lung cancers
Overview of the initial evaluation, treatment and prognosis of lung cancer
Pancoast's syndrome and superior (pulmonary) sulcus tumors
Pathology of lung malignancies
Role of imaging in the staging of non-small cell lung cancer
Sequential non-cross-resistant therapy for patients responding to initial treatment of advanced non-small cell lung cancer
Small molecule epidermal growth factor receptor inhibitors for advanced non-small cell lung cancer
Overview of the treatment of advanced non-small cell lung cancer
Targeted agents in the initial systemic treatment of advanced non-small cell lung cancer
Hospice: Philosophy of care and appropriate utilization

The following organizations also provide reliable health information.

• National Cancer Institute

      1-800-4-CANCER
      (www.nci.nih.gov)

• American Society of Clinical Oncology

      (www.cancer.net/portal/site/patient)

• National Comprehensive Cancer Network

      (www.nccn.com)

• Global Resource for Advancing Cancer Education (GRACE)

      (www.cancerGRACE.org/lung)

• Lung Cancer Alliance

      (www.lungcanceralliance.org)

[1-3]