Patient information: Small cell lung cancer treatment (Beyond the Basics)
- Gregory P Kalemkerian, MD
Gregory P Kalemkerian, MD
- Professor of Medicine
- Co-Director, Thoracic Oncology
- University of Michigan Medical Center
SMALL CELL LUNG CANCER OVERVIEW
Lung cancer is categorized into two basic disease types: small cell lung cancer and non-small cell lung cancer based on the appearance of the cancer cells under the microscope and the behavior of the disease. Small cell lung cancer makes up about 15 percent of all lung cancers, with the remainder being non-small cell lung cancer.
Small cell lung cancer occurs almost exclusively in smokers, particularly heavy smokers, and former smokers. It is usually an aggressive cancer that tends to grow and spread quickly. Because of this, surgery is useful for very few patients with small cell lung cancer.
Non-small cell lung cancer is discussed in detail in separate topic reviews. (See "Patient information: Non-small cell lung cancer treatment; stage I to III cancer (Beyond the Basics)" and "Patient information: Non-small cell lung cancer treatment; stage IV cancer (Beyond the Basics)".)
SMALL CELL LUNG CANCER CLASSIFICATION
The "stage" of a cancer refers to a formal classification of the extent of disease within an individual patient. A variety of imaging tests (eg, computed tomography [CT] scans, magnetic resonance imaging [MRI] scans, positron emission tomography [PET] scans, bone scans) can be used to identify cancer in different parts of the body. Sometimes, additional biopsies are needed to confirm the presence or absence of cancer in a particular site. The stage of the cancer is important in determining the most appropriate treatment for an individual patient.
Patients with small cell lung cancer are traditionally classified as having either limited-stage or extensive-stage disease. Many experts have recommended that small cell lung cancer should be classified using the same system that is used for non-small cell lung cancer, with classifications as stage I, II, III, or IV, in order to provide a more detailed assessment of the extent of disease. (See "Patient information: Lung cancer risks, symptoms, and diagnosis (Beyond the Basics)".)
Limited-stage disease — Limited-stage small cell lung cancer is defined as cancer within only one lung and/or in the lymph nodes in the mediastinum (the area in the middle of the chest between the two lungs). Limited-stage disease correlates with stage I, II, or III cancer using the more detailed staging system. About one-third of patients with small cell lung cancer have limited-stage disease at the time they are diagnosed. However, in many cases, the cancer will have already spread outside of the chest, but is not visible on any available imaging tests.
Most people with limited-stage small cell lung cancer are treated with chemotherapy in combination with radiation therapy directed at the disease in the chest. After this initial treatment, patients are frequently treated with radiation therapy to the brain in order to prevent the development of brain metastases and to improve survival. The goal of treatment for limited-stage disease is to cure the patient of the cancer.
In the rare patient with very early-stage disease (stage I) where the only site of cancer is a single tumor within one lung, surgery should be considered. In such situations, surgery is then followed by chemotherapy with or without radiation therapy (figure 1).
Extensive-stage disease — Most patients with small cell lung cancer have extensive-stage disease at the time of initial diagnosis. This means that the cancer has spread either to the other side of the chest or to more distant locations in the body. Common sites of spread include the other lung, liver, adrenal glands, bones, or brain. Patients with extensive-stage small cell lung cancer are generally treated with chemotherapy; surgery is not an option. Extensive-stage disease is not considered to be curable, and the goals of treatment are to relieve symptoms caused by the cancer and to prolong life. People who respond well to chemotherapy are often given radiation therapy to the brain to prevent the development of brain metastases, and may also receive radiation therapy to the chest. Radiation therapy may also be used to treat other areas of the body to relieve symptoms caused by the spread of cancer. (See 'Brain radiation' below.)
Chemotherapy refers to the use of medicines to either kill cancer cells or stop their growth. It is the mainstay of treatment for small cell lung cancer. Chemotherapy works by interfering with the ability of rapidly growing cells (such as cancer cells) to divide or reproduce. Because most of an adult's normal cells are not actively growing, they are not affected much by chemotherapy, with the exception of bone marrow (where the blood cells are produced), hair follicles, and the lining of the gastrointestinal tract (eg, stomach, intestines). Effects of chemotherapy on these and other normal tissues gives rise to side effects seen during treatment. (See 'Side effects' below.)
A number of chemotherapy drugs are active against small cell lung cancer, and many new drugs are being explored in clinical trials. Patients with small cell lung cancer may be treated with a single chemotherapy drug, although it is more common, and usually more effective, to use a combination of two chemotherapy drugs given together. This improves the chance of reducing the size of the tumor (termed a response to therapy) and modestly prolongs patient survival. Chemotherapy is usually administered as an injection into the vein (intravenously), although some drugs can be given by mouth.
Generally speaking, chemotherapy is administered over a one- to three-day period, usually every three weeks, and then restarted again. The waiting period is necessary to allow the effects of the drugs on normal tissues to subside before administering more chemotherapy. The short period of drug administration followed by the waiting period is called one "cycle" of chemotherapy.
Duration of treatment — The optimal duration of initial chemotherapy for patients with small cell lung cancer is determined by how the cancer is responding to treatment, and how the patient's body tolerates the treatment. Typically, four to six cycles of initial chemotherapy are recommended. Additional cycles of chemotherapy (called maintenance chemotherapy) have not been shown to significantly improve survival or quality of life.
Limited-stage disease — The most commonly used combination of chemotherapy drugs for patients with limited-stage small cell lung cancer is cisplatin (Platinol) plus etoposide (VP-16, VePesid). Due to the high rate of side effects associated with cisplatin, a related drug called carboplatin (Paraplatin) is frequently used in its place and appears to be equally effective in treating the disease.
Extensive-stage disease — Patients with extensive-stage small cell lung cancer are often treated with cisplatin or carboplatin in combination with either etoposide or irinotecan (Camptosar). In Japanese patients, irinotecan may be more effective than etoposide, but in Caucasian patients, the two drugs have demonstrated similar benefits with less severe side effects noted in patients receiving etoposide.
Side effects — Chemotherapy affects normal cells as well as cancer cells, resulting in a wide range of potential side effects. While receiving chemotherapy, patients are closely monitored for these side effects.
The most important side effect of chemotherapy is a transient drop in the blood counts due to the effect of chemotherapy on the bone marrow. This typically occurs one to two weeks after a dose of chemotherapy is given. During this time, the patient or a family member should report any fever or chills to the clinician; having low blood counts can increase a person's chances of developing infections, such as pneumonia, which can be life-threatening.
Other possible side effects of chemotherapy include fatigue, hair loss, nausea, vomiting, numbness or pain in the fingers and toes, hearing loss, diarrhea, mouth sores, decreased appetite, changes in taste, and impairment of kidney function.
Radiation therapy is usually recommended during chemotherapy for people with limited-stage small cell lung cancer. Radiation therapy involves the use of high-energy x-rays focused on the specific sites of disease to kill cancer cells. The x-rays are delivered from a machine (called a linear accelerator) that is outside of the patient’s body, and individual treatments are brief (typically 10 to 15 minutes) and not painful.
The damaging effect of radiation is cumulative (additive), and a certain amount of radiation must be delivered before the cancer cells are so damaged that they die. To accomplish this, small radiation doses are administered daily, five days per week, for five to seven weeks. Sometimes, for patients with limited-stage disease, radiation is delivered twice daily, five days per week, for three weeks. Radiation is administered to the areas of the body that are affected by the cancer. Thus, in contrast to chemotherapy, which is a systemic or body-wide treatment, radiation is a local treatment, and side effects are generally limited to the area undergoing radiation.
Chest radiation — Studies of patients with limited-stage small cell lung cancer have shown that radiation to the chest can decrease the chance of the cancer re-growing in the chest (a recurrence) after initial treatment. Furthermore, the use of radiation improves the likelihood of being cured of the cancer.
Chemotherapy and radiation therapy are usually started at the same time (called concurrent therapy). Chest radiation can sometimes be given after chemotherapy has been completed (called sequential therapy), particularly in people who have very large tumors or who are very sick when they are initially diagnosed with the cancer.
When radiation is given at the same time as chemotherapy (concurrent chemoradiotherapy), the side effects of both treatments are usually more pronounced (eg, lowering of the blood counts). However, the benefit of each treatment is greater when they are given concurrently rather than sequentially.
Radiation therapy to the chest is also used in some patients with extensive-stage small cell lung cancer who have had a good response to initial chemotherapy but still have disease present in their lung or lymph nodes.
Side effects related to radiation occur gradually over the weeks of treatment. They include fatigue, mild skin reddening of the chest and back, and difficult or painful swallowing due to inflammation of the inner lining of the esophagus (esophagitis). These esophageal symptoms are closely monitored and can be treated with appropriate pain medications. Long-term side effects can occur many months after radiation has been completed and include inflammation and/or scarring of the normal lung surrounding the cancer (pneumonitis), which can be associated with coughing, shortness of breath, and increased sputum production.
Brain radiation — The brain is a common site of tumor spread (termed metastasis) in people with small cell lung cancer. In patients with both limited-stage and extensive-stage disease who have normal brain scans after initial treatment (chemotherapy or chemotherapy plus radiation), preventive radiation treatment to the brain can substantially reduce the chance of developing brain metastases and prolong survival. This type of radiation therapy is called prophylactic cranial irradiation, or PCI. PCI is often recommended for people if the cancer in the rest of the body has partially or completely responded to the initial course of chemotherapy or chemoradiotherapy.
Using modern techniques, PCI causes a tolerable level of short-term side effects, including redness and itching of the scalp, fatigue, and hair loss, all of which usually improve over the weeks to months after PCI. Long-term side effects are uncommon, but may include neurologic and intellectual difficulties such as short-term memory loss, difficulty concentrating, and instability when walking. Such side effects are more common in elderly people who receive PCI, so the risks and benefits of PCI need to be very carefully considered in people over 70 years old and in those with underlying neurological problems. The likelihood of long-term side effects is lessened when PCI and chemotherapy are given at different times.
In patients who already have spread of small cell lung cancer to the brain or who subsequently develop brain metastases, radiation therapy to the brain is usually recommended to control symptoms and improve quality of life.
THE ROLE OF SURGERY IN SMALL CELL LUNG CANCER
Because small cell lung cancer spreads quickly, surgery to remove the lung tumor generally does not improve the probability or duration of patient survival. However, it may be beneficial in a small number (less than 5 percent) of patients who are diagnosed very early in the course of their disease. In these patients, surgery followed by chemotherapy can result in a five-year survival rate of up to 35 to 40 percent.
Surgery appears to be most helpful for patients with a single tumor confined to one lobe of the lung with no evidence of spread of the cancer to lymph nodes or any other part of the body. Thus, before surgery is considered, a procedure called a mediastinoscopy is usually performed by a thoracic surgeon. In this procedure, a thin tube (scope) is inserted through the skin above the breast bone (sternum) and into the mediastinum (the middle part of the chest between the right and left lungs (figure 2)). Samples of tissue, usually lymph nodes, can then be withdrawn through the tube and examined with a microscope to determine if cancer cells are present. If these lymph nodes do not contain any visible cancer cells, then surgical removal of the lung cancer followed by chemotherapy, with or without radiation therapy, is a reasonable treatment strategy.
EFFECTIVENESS OF SMALL CELL LUNG CANCER TREATMENT
Chemotherapy is of clear benefit in patients with small cell lung cancer, improving both quality of life and duration of survival. Without chemotherapy, the average survival of patients with small cell lung cancer is usually measured in weeks. Although small cell lung cancer is an aggressive disease, it responds well to initial chemotherapy and radiation. The goal of treatment for people with limited-stage small cell lung cancer is cure, which is achieved in 20 to 25 percent of patients. In limited-stage disease, the likelihood of responding to chemotherapy and radiation therapy is high, with significant tumor shrinkage noted in 80 to 100 percent of patients, about half of whom have a complete response (no remaining evidence of the cancer by either physical examination or scans). Unfortunately, most patients will have a recurrence of disease, which is typically more resistant to subsequent therapy.
Extensive-stage small cell lung cancer is not considered to be a curable disease. The goals of therapy are to relieve symptoms, maintain quality of life, and prolong patient survival. Chemotherapy still offers a high rate of response, with 60 to 80 percent of patients having significant tumor shrinkage and 10 to 15 percent achieving a complete response.
Despite these favorable results, small cell lung cancer tends to recur or relapse within one to two years in the majority of patients. If small cell lung cancer recurs or fails to respond to one type of chemotherapy, a different type of chemotherapy may offer some relief from symptoms and a modest improvement in survival.
Smoking cessation — The importance of quitting smoking cannot be overemphasized, particularly for patients with limited-stage disease. Patients who continue to smoke do not do as well as those who quit. One reason is that if they survive their first lung cancer, they have a substantial chance of developing a second lung cancer because of continued smoking. Furthermore, treatment with chemotherapy, radiation therapy, and surgery can cause further lung damage. It is therefore important to have the best lung function possible prior to and after receiving treatment. Thus, if at all possible, patients should stop smoking. (See "Patient information: Quitting smoking (Beyond the Basics)".)
This is also an important opportunity to encourage family and friends to stop smoking. There are inherited genetic factors that increase the likelihood of getting lung cancer, especially if a person with these genetic factors smokes or is around those who do.
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:
Videos addressing common questions about clinical trials are available from the American Society of Clinical Oncology (http://www.cancer.net/pre-act).
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 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 — UpToDate offers two types of patient education materials.
The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.
Patient information: Non-small cell lung cancer treatment; stage I to III cancer (Beyond the Basics)
Patient information: Non-small cell lung cancer treatment; stage IV cancer (Beyond the Basics)
Patient information: Lung cancer risks, symptoms, and diagnosis (Beyond the Basics)
Patient information: Quitting smoking (Beyond the Basics)
Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.
Extensive stage small cell lung cancer: Initial management
Pathobiology and staging of small cell carcinoma of the lung
Prophylactic cranial irradiation for patients with small cell lung cancer
Role of surgery in multimodality therapy for small cell lung cancer
Sequelae and complications of pneumonectomy
Limited stage small cell lung cancer: Initial management
Treatment of refractory and relapsed small cell lung cancer
The following organizations also provide reliable health information.
●The National Library of Medicine
●National Cancer Institute
●American Society of Clinical Oncology
●Global Resource for Advancing Cancer Education (GRACE)
All topics are updated as new information becomes available. Our peer review process typically takes one to six weeks depending on the issue.