Treatment of small cell lung cancer

INTRODUCTION — Small cell lung cancer (SCLC) makes up about 15 to 25 percent of all lung cancers. The majority of lung cancers, 75 to 85 percent, are called non-small cell lung cancers, and they behave differently from SCLCs. (See "Patient information: Treatment of early stage (stage I and II) non-small cell lung cancer" and see "Patient information: Treatment of locally advanced (stage III) non-small cell lung cancer" and see "Patient information: Treatment of advanced unresectable; metastatic; and recurrent non-small cell lung cancer").

SCLC occurs almost exclusively in smokers, particularly heavy smokers, and tends to grow and spread quickly. Because of this, surgery is considered less often in patients with SCLC than with non-small cell lung cancer.

CLASSIFICATION — For the purpose of treatment, SCLC is classified as either limited disease or extensive disease. (See "Patient information: Diagnosis and staging of lung cancer").

Limited disease — In limited disease, the cancer is present within the lung on only one side of the chest and/or in the central lymph nodes. About one-third of patients with SCLC have limited disease at the time they are diagnosed. However, almost all of these patients will already have spread of the cancer outside of the chest in a way that is not yet clinically apparent or visible on radiologic imaging. Patients are generally treated with chemotherapy in combination with radiation therapy. In rare cases, surgery may be considered.

Extensive disease — In patients with extensive disease, the cancer has spread to the other side of the chest, or to more distant locations in the body. Patients generally receive chemotherapy alone, radiation therapy is only sometimes used, and surgery is not an option.

CHEMOTHERAPY — Chemotherapy refers to the use of medicines to stop or slow the growth of cancer cells. It is the mainstay of treatment for SCLC. Chemotherapy works by interfering with the ability of rapidly growing cells (like cancer cells) to divide or reproduce themselves. Because most of an adult's normal cells are not actively growing, they are not affected as much by chemotherapy, with the exception of bone marrow (where the blood cells are produced), the hair, and the lining of the gastrointestinal tract. Effects of chemotherapy on these and other normal tissues gives rise to side effects during treatment (see below).

A number of chemotherapy drugs are active against SCLC, and many new drugs are being explored. A single chemotherapy drug may be used to treat SCLC, although more commonly combination therapy (the combined use of two or more chemotherapy drugs given together) is used. This improves the chance of reducing the size of the tumor (termed a response to therapy), and modestly lengthens survival. Chemotherapy is usually administered as an injection into the vein (intravenously), although some agents can be given by mouth.

The most commonly used drug combination for patients with limited stage SCLC is cisplatin plus etoposide. Patients with extensive stage disease are often treated with cisplatin or carboplatin in combination with either etoposide or irinotecan.

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. The number of cycles is determined by how the cancer is responding to treatment, and how the patient's body is tolerating the treatment. Typically, four to six cycles of chemotherapy are administered to patients with SCLC.

Side effects — As noted above, chemotherapy affects some normal cells as well as the cancer cells, resulting in a range of possible side effects. While receiving chemotherapy, patients must be closely monitored for these side effects and any signs of drug toxicity.

The most important side effect is a transient drop in the blood counts due to the effect of chemotherapy on the bone marrow. This typically occurs in the midpoint of the waiting period. During this time, any fever or chills should immediately be reported to the patient's physician because having low blood counts can lower resistance to infection; in particular, many patients with SCLC are prone to getting pneumonia. Other possible side effects include fatigue, hair loss, numbness in the fingers and toes, hearing loss, diarrhea, and changes in kidney function.

RADIATION THERAPY — Radiation therapy (RT) to the chest is often used along with chemotherapy to treat patients with limited SCLC. Radiation therapy (RT) involves the use of focused, high energy x-rays to destroy cancer cells. The x-rays are delivered from a machine (called a linear accelerator) that is outside of the patient, and individual treatments are brief (typically 10 to 15 minutes) and not painful.

The damaging effect of radiation is cumulative, and a certain dose must be reached 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. Radiation is only administered to the areas of the body that are affected by the tumor. 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 disease have shown that RT can help decrease the chance of the tumor regrowing in the chest (termed a recurrence) following chemotherapy. Furthermore, the use of radiation in this setting may also improve the likelihood of surviving the cancer by approximately five percent [1].

The best way of combining the radiation with chemotherapy is a matter of debate, although in general, chemotherapy and radiation therapy are usually started together (called concurrent therapy). Radiation can sometimes be given after chemotherapy has been completed (called sequential therapy). With concurrent therapy, the side effects of both treatments are usually more pronounced (eg, lowering of the blood counts, difficulty swallowing due to inflammation of the lining of the esophagus [termed esophagitis], and inflammation of the normal lung surrounding the tumor [termed pneumonitis]). However, most experts believe that the degree of benefit is higher when the treatments are given concurrently.

Brain radiation — Because the brain is a common site of tumor spread (termed metastasis) in patients with SCLC, patients with limited disease may also receive radiation therapy to the brain with the hope that it will prevent brain metastasis (called prophylactic cranial irradiation, or PCI). This type of treatment reduces the chance of a patient developing a brain metastasis by one-half, and some studies also suggest a modest improvement in survival, particularly in patients with a complete response to chemotherapy (see below) [2].

In patients who already have spread of SCLC to the brain, RT may be needed to control symptoms.

The toxicity of PCI is an important factor. Side effects during treatment include redness and itching of the scalp, fatigue, and hair loss, all of which are usually self-limited. Longer-term effects are more difficult to quantify, but may include both neurologic and intellectual disabilities (memory loss and difficulty concentrating). The likelihood of these long-term effects are lessened if PCI and chemotherapy are not given at the same time.

THE ROLE OF SURGERY — Because SCLC spreads quickly, surgery to remove the lung tumor generally does not improve the probability or length of survival. However, it may be beneficial in a small number (less than 10 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.

Mediastinoscopy — Surgery appears to be most helpful for patients whose lymph nodes are not yet affected by the disease (show picture 1). Thus, before surgery is considered, a procedure called a mediastinoscopy is usually performed. This is generally performed by a thoracic surgeon after the patient receives general anesthesia. A thin tube is inserted through the chest wall and into the mediastinum, the central portion of the chest that represents the space between the right and left lung. A sample of tissue can then be withdrawn through the tube. The tissue is examined with a microscope to determine if cancer cells are present.

EFFECTIVENESS OF TREATMENT — Chemotherapy is of clear benefit in patients with SCLC. Without chemotherapy, the average survival is measured in weeks. The likelihood of responding to chemotherapy with or without radiation therapy is quite high. Response rates of 80 to 100 percent are seen in patients with limited disease, and approximately one-half of these are complete (no remaining evidence of the cancer by either physical examination or x-ray studies) [3,4]. With extensive stage disease, 60 to 80 percent of patients will respond to chemotherapy, and between 15 and 40 percent will have a complete response.

Despite these favorable results, SCLC tends to recur or relapse within one to two years in the majority of patients, particularly those with extensive stage disease. If the SCLC recurs or fails to respond to one type of chemotherapy regimen, a different type of chemotherapy regimen 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 less well. One reason is that if they survive their first lung cancer, they have a substantial chance of developing a second lung cancer because of smoking. Furthermore, treatment with chemotherapy, radiation therapy, and surgery can cause 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: Smoking cessation").

This is also an important opportunity for family and friends to stop smoking. There are inherited genetic factors that increase the likelihood of getting lung cancer, especially if persons with these genetic factors smoke or are around those who do.

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. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Cancer Institute

(www.cancernet.nci.nih.gov/)
People Living With Cancer: The official patient information

website of the American Society of Clinical Oncology
(www.plwc.org/portal/site/PLWC)
The American Cancer Society

(www.cancer.org)
Lung Cancer Alliance

(www.lungcanceralliance.org)



Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Pignon, JP, Arriagada, R, Ihde, DC, et al. A meta-analysis of thoracic radiotherapy for small-cell lung cancer. N Engl J Med 1992; 327:1618.
2. Auperin, A, Arriagada, R, Pignon, JP, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med 1999; 341:476.
3. Ciombor, KK, Rocha Lima, CM. Management of small cell lung cancer. Curr Treat Options Oncol 2006; 7:59.
4. Jackman, DM, Johnson, BE. Small-cell lung cancer. Lancet 2005; 366:1385.