Chemotherapy for Stage IV Non-Small Cell Lung Cancer

September 6, 2011

To help doctors give their patients the best possible care, the American Society of Clinical Oncology (ASCO) developed evidence-based recommendations on the treatment of stage IV non-small cell lung cancer. This guide for patients contains several recommendations, one of which was updated in September 2011.

Key Messages:

  • Chemotherapy for stage IV non-small cell lung cancer may lengthen a patient's life and improve his or her quality of life.
  • This patient guide discusses which drugs, and which combination of drugs, are best for patients with stage IV non-small cell lung cancer based on results from clinical trials. These recommendations depend on the patient and the type of treatment he or she has already received.
  • Talk with your doctor about your health and the treatment options that are best for you. Treatment of the symptoms and side effects from the cancer and cancer treatments is also an important part of your care.


Lung cancer begins when normal cells in the lungs change and grow uncontrollably, forming a mass called a tumor. There are two major types of lung cancer: non-small cell lung cancer and small cell lung cancer. Non-small cell lung cancer (NSCLC) is the most common type. NSCLC and small cell lung cancer are treated in different ways. This guide covers chemotherapy treatment options for people with stage IV NSCLC.

Stage is a way to describe a cancer, such as how much it has grown and whether it has spread to other parts of the body. Lung cancer may spread to the lymph nodes, the tiny, bean-shaped organs that help fight infection, and other parts of the body, specifically the brain, bones, liver, and/or adrenal glands. Stage IV NSCLC has spread to more than one part of the lung or other distant parts of the body. Learn more about lung cancer staging or treatment options for other stages of lung cancer.

Chemotherapy for NSCLC

People with stage IV NSCLC usually receive chemotherapy, which is the use of drugs to kill cancer cells. This is the only treatment that will go everywhere in the body and destroy cancer cells wherever they may be located. Chemotherapy has been shown to improve both length of life and quality of life for patients with NSCLC. However, chemotherapy will not get rid of the cancer completely or cure it. The goal of chemotherapy for stage IV NSCLC is to control the disease so that it will stop growing and spreading. Patients must be prepared to take chemotherapy, on and off, for the rest of their lives to maintain control of the disease. Most chemotherapy used for lung cancer is injected into a vein (called intravenous, or IV injection). Other drugs are pills that can be taken by mouth. There are many different drugs, and drug combinations, from which the doctor and patient can choose. The first drug or combination of drugs a patient takes is called “first-line” treatment, which may be followed by “second-line” and “third-line” treatment. People with stage IV NSCLC may also consider a clinical trial or supportive or palliative care (see below).

The side effects of chemotherapy for NSCLC vary widely, depending on the drug or drug combinations and should be discussed with the doctor before starting treatment. Side effects may include fatigue, low blood cell counts, risk of infection, hair loss, rash, mouth sores, nausea and vomiting, loss of appetite, diarrhea, hearing problems, numbness or tingling in the hands and feet, or swelling in the ankles. Learn about managing side effects of cancer treatments.

Most types of chemotherapy kill cancer cells by destroying rapidly growing cells, which is why these drugs also affect blood cells and hair cells. Other types of drugs, called targeted therapies, target the cancer's specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. These drugs include bevacizumab (Avastin), cetuximab (Erbitux), and erlotinib (Tarceva), and gefitinib (Iressa; not available in the United States). This type of treatment blocks the growth and spread of cancer cells while limiting damage to normal cells; however, they may cause side effects, such as high blood pressure or bleeding (bevacizumab), rash (cetuximab, erlotinib, gefitinib), and diarrhea (erlotinib, gefitinib).

No specific treatment or combination of treatments works for every patient. If the first-line treatment causes unpleasant or dangerous side effects, does not appear to be working, or stops working, the doctor may recommend a change in treatment.

Performance Status

When making treatment decisions with patients, doctors evaluate a patient's ability to carry out daily activities using an index (zero [0] through four [4]) called performance status. A performance status rating of 0 or 1 means that a person is able to move around easily, be out of bed for more than half the day, and take care of oneself relatively easily. A person who is strong enough to go about his or her daily activities without assistance, including working outside the home, can typically receive chemotherapy and targeted therapy. A performance status rating of 2 means a person cannot do any work, but can still take care of himself or herself and is out of bed for more than half of the day. A patient's performance status is an important factor in helping the doctor and patient decide on treatment options. For example, doctors may recommend targeted therapy, and rarely chemotherapy, for a person with a performance status of 2. Other illnesses, such as heart disease, emphysema, and diabetes may affect a patient's performance status.

Supportive Care

In addition to treatment to slow or stop the cancer (also called disease-directed treatment), an important part of cancer care is relieving a person's symptoms and side effects. It includes supporting the patient with his or her physical, emotional, and social needs, an approach called palliative or supportive care. People often receive disease-directed therapy and treatment to ease symptoms at the same time. Supportive care is always an option for a person with stage IV NSCLC.


ASCO's recommendations for chemotherapy for stage IV NSCLC depend on the patient's performance status and whether a patient is receiving a first-line, second-line, or third-line treatment. ASCO recommends the following for all patients:

  • Any patient with good performance status (performance status 0, 1, and possibly 2) should be able to receive chemotherapy. Older patients should not be prevented from receiving chemotherapy based on age alone. Performance status and the patient's overall health are more important factors than age in considering chemotherapy as a treatment option.

ASCO recommends the following for patients receiving first-line treatment:

  • The most effective chemotherapy for most patients with performance status 0 and 1 is a combination of two drugs in which one is either carboplatin (Paraplat, Paraplatin) or cisplatin (Platinol). Cisplatin is slightly more effective, but has more side effects than carboplatin, so either is acceptable, depending on the doctor's and the patient's preferences. Types of chemotherapy that may be combined with cisplatin or carboplatin include docetaxel (Taxotere), gemcitabine (Gemzar), irinotecan (Camptosar), paclitaxel (Taxol), pemetrexed (Alimta), and vinorelbine (Navelbine).
  • Patients with a performance status of 2 may receive only one drug because there is not enough evidence to recommend taking more than one drug at a time. When a patient takes only one drug, it is typically not carboplatin or cisplatin, but rather one of the drugs commonly paired with carboplatin or cisplatin.
  • For patients with a performance status of 3 (in bed or a chair more than half the day), chemotherapy has not been shown to improve quality or length of life and may cause harmful side effects that could worsen a patient's quality of life. In this situation, patients should concentrate on supportive care to improve symptoms and take chemotherapy only with special caution.
  • Once a patient starts chemotherapy, treatment should be changed if it causes dangerous or difficult side effects. Chemotherapy should be stopped if the cancer grows, or if after four cycles, the cancer is stable but treatment is not causing the tumor to shrink. Two drug combinations should be given for no more than six cycles (up to five months). For patients with stable disease or cancer that is responding to treatment after four cycles, the doctor may consider immediately starting treatment with another drug, such as pemetrexed (patients with non-squamous cell carcinoma), docetaxel, or erlotinib. Or, the doctor might wait to start second-line chemotherapy until the cancer starts to grow again.
  • Most patients should not receive the drugs gefitinib or erlotinib as part of their first-line treatment.
  • However, some patients may receive either of these drugs and other targeted treatments as part of their first-line chemotherapy.
    • Erlotinib (or gefitinib for patients outside the United States) alone may be recommended for patients with tumors that have a mutation (change) in the epidermal growth factor receptor (EGFR) gene, which can be detected by testing the piece of lung cancer removed during a biopsy (removal of a small amount of tissue for examination under a microscope).
    • For patients receiving cisplatin and vinorelbine, cetuximab may be added.
    • Bevacizumab may be added to carboplatin and paclitaxel, except for patients who have a specific type of NSCLC called squamous cell carcinoma, or who have a history of coughing up blood, or have had a recent heart attack, blood clot, stroke, or bleeding, or brain metastases.

ASCO recommends the following for second-line treatment for patients with stage IV NSCLC:

  • Patients can receive one of the following drugs: docetaxel, erlotinib, gefitinib, or pemetrexed, when the first treatment is no longer effective. There is no evidence that combining treatments is effective or safe for second-line treatment, nor is there enough data to recommend how long a patient should receive a drug.

For patients receiving a third-line treatment, ASCO recommends the following:

  • For patients with a performance status of 0 to 3, erlotinib is recommended, as long as they have not previously received this drug or gefitinib. There is not enough evidence to make a recommendation for or against other types of chemotherapy for third-line treatment.

Lastly, ASCO recognizes that most patients with NSCLC may not have any special molecular tests, such as one to detect an EGFR mutation, performed on their tumor. These molecular tests remain investigational, and selecting treatment based on molecular tests has not been shown to improve a patient's overall length of life. Therefore, ASCO does not recommend using any routine molecular analysis of tumor tissue to guide treatment decisions at this time. For patients with an EGFR mutation, erlotinib or gefitinib may be the best first-line therapy, but may also work well as a second or third-line treatment.

To aid future research, ASCO recommends that doctors obtain a larger tissue sample when performing a biopsy so that the samples can be tested, which may be required for patients to participate in some types of clinical trials.

What This Means for Patients

Chemotherapy for stage IV lung cancer may help lengthen and improve the quality of life for many patients with stage IV NSCLC. ASCO recommends different drug combinations based on a patient's performance status, overall health, and previous treatments. A patient's age should never be used as the only reason for deciding which treatment is best. It's important that patients and their families talk with the doctor about the benefits and risks of chemotherapy to help them choose the care that will help maintain or improve their quality of life. Many of these drugs cause different side effects and discussing the possible side effects of these treatments, both as single drugs and in combinations, and how to effectively manage or prevent any side effects can help patients make informed decisions about their care.

If disease-directed treatment is not successful, treatment may then focus on palliative or supportive care. This diagnosis is stressful, and it may be difficult to discuss. However, it is important to have open and honest conversations with your doctor and health care team to express your feelings, preferences, and concerns. The health care team is there to help, and many team members have special skills, experience, and knowledge to support patients and their families. Learn more about advanced cancer care planning.

Questions to Ask the Doctor

To learn more about your treatment options for stage IV NSCLC, consider asking your doctor the following questions:

  • What type of lung cancer do I have?
  • What is the stage of the cancer? What does this mean?
  • What is my performance status? What does this mean?
  • What are my treatment options?
  • What clinical trials are open to me?
  • Which treatment option do you recommend? Why?
  • What are the benefits of this treatment?
  • How will this treatment affect my daily life? Will I be able to work, exercise, and perform my usual activities?
  • What are the names of the drugs, and how are they given?
  • What are the side effects of each drug?
  • What can be done to lessen these side effects?
  • Will some of the side effects end when the treatment ends? Will some last longer?
  • Can you or your team help me cope with the side effects of cancer if I decide not to receive chemotherapy, or when chemotherapy is no longer effective?
  • How often will I need to visit the doctor to receive treatment, and how long will each visit take?
  • Will I be able to go to and return from this treatment on my own, or should I arrange to have assistance?
  • If I'm worried about managing the costs related to my cancer care, who can help me with these concerns?
  • What support services are available to me? To my family?
  • Are there any other concerns or issues I should address at this time?
Decision Aids

To help patients talk with their doctor about chemotherapy for stage IV lung cancer, ASCO has created several decision aids. These tools provide information on the risks and benefits of chemotherapy, help for thinking through the decision, and other issues for patients to consider. Use one of these decision aids to begin a discussion with your doctor.

First-Line Chemotherapy Decision Aid

Second-Line Chemotherapy Decision Aid

Second-Line or Third-Line Chemotherapy with Erlotinib Decision Aid

Third-Line or Fourth-Line Chemotherapy Decision Aid

Helpful Links

Read the entire clinical practice guideline at

Guide to Lung Cancer

Understanding Chemotherapy