Small cell lung cancer treatment

Small cell lung cancer treatment

Authors
Anthony Elias, MD
Elizabeth H Baldini, MD, MPH
Section Editor
Arthur T Skarin, MD
Deputy Editor
Michael E Ross, MD

Disclosures

SMALL CELL LUNG CANCER OVERVIEW — Small cell lung cancer 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 small cell lung cancer than with non-small cell lung cancer.

Small cell lung cancer (SCLC) makes up about 15 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 small cell lung cancers.

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” and “Patient information: Non-small cell lung cancer treatment; stage IV cancer”.)

SMALL CELL LUNG CANCER CLASSIFICATION — For the purpose of treatment, a person with small cell lung cancer is classified as having either limited disease or extensive disease. (See “Patient information: Lung cancer risks, symptoms, and diagnosis”.)

Limited lung disease — In people with limited lung 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 small cell lung cancer have limited disease at the time they are diagnosed. However, in almost all cases, the cancer will have spread outside of the chest in a way that is not yet visible with imaging tests. Most people with limited disease are treated with chemotherapy in combination with radiation therapy. In early stage (stage I/II) disease amenable to lobectomy, surgery should be considered, although these cases are rare.

Extensive lung disease — In patients with extensive lung disease, the cancer has spread to the other side of the chest, or to more distant locations in the body. Patients are generally given chemotherapy as the initial treatment; surgery is not an option. People who respond to chemotherapy are often given radiation therapy to the brain to prevent the development of brain metastases. (See ‘Brain radiation’ below.)

SMALL CELL LUNG CANCER CHEMOTHERAPY — Chemotherapy refers to the use of medicines to stop or slow the growth of cancer cells. It is the mainstay of treatment for small cell lung cancer. 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 ‘Side effects’ below).

A number of chemotherapy drugs are active against small cell lung cancer, and many new drugs are being explored. A single chemotherapy drug may be used to treat small cell lung cancer, 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.

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 not well defined. The number of cycles 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 chemotherapy are recommended. Additional cycles of chemotherapy (called maintenance chemotherapy) have not been shown to significantly improve survival or quality of life.

Limited lung disease — The most commonly used drug combination for patients with limited stage small cell lung cancer is cisplatin plus etoposide.

Extensive lung disease — Patients with extensive stage lung disease are often treated with cisplatin or carboplatin in combination with either etoposide or irinotecan.

Side effects — Chemotherapy affects normal cells as well as the cancer cells, resulting in a wide range of side effects. While receiving chemotherapy, patients are closely monitored for these side effects and any signs of toxicity.

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 physician; having low blood counts can increase a person’s chances of developing infections, such as pneumonia.

Other possible side effects of chemotherapy include fatigue, hair loss, nausea, numbness in the fingers and toes, hearing loss, diarrhea, and changes in kidney function.

SMALL CELL LUNG CANCER RADIATION THERAPY — Radiation therapy (RT) is often recommended during chemotherapy for people with limited small cell lung cancer. 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 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 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 lung disease have shown that RT to the chest can help decrease the chance of the tumor regrowing in the chest (a recurrence) after chemotherapy. Furthermore, the use of radiation may improve the likelihood of surviving the cancer by approximately five percent [1].

The best way of combining chest RT with chemotherapy is a matter of debate, although in general, chemotherapy and radiation therapy are usually started at the same time (called concurrent therapy). Chest RT 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 (esophagitis), and inflammation of the normal lung surrounding the tumor (pneumonitis)). However, most experts believe that the benefit of each treatment is greater when they are given concurrently.

Side effects related to radiation occur gradually over the weeks of treatment. They include fatigue, possible mild skin reddening of the chest, and esophageal symptoms characterized by an initial feeling of a “lump in one’s throat” when swallowing and eventually, a sore throat (esophagitis). The esophageal symptoms are closely monitored and treated with appropriate pain medications. Long-term side effects occur many months after radiation has been completed and include scarring of normal lung, which can be seen on follow up chest CT scans and is sometimes associated with shortness of breath.

Brain radiation — The brain is a common site of tumor spread (termed metastasis) in people with small cell lung cancer. Having preventive radiation treatment of the brain after chemotherapy, before evidence of metastases develop, substantially reduces the chances of developing brain metastases and prolongs survival [2,3]. This type of radiation therapy is called prophylactic cranial irradiation, or PCI. PCI is often recommended for people with limited or extensive disease if the tumor has partially or completely responded to the initial course of chemotherapy [3].

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 are usually self-limited. Long-term side effects may include mild neurologic and intellectual difficulties (including short-term memory loss and difficulty concentrating). The likelihood of these long-term 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 and in those who subsequently develop brain metastases, radiation therapy to the brain is often recommended to control symptoms.

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 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. 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 skin of the chest wall and into the mediastinum, the central portion of the chest that represents the space between the right and left lung (figure 1). 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 SMALL CELL LUNG CANCER TREATMENT — Chemotherapy is of clear benefit in patients with small cell lung cancer. 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) [4,5]. 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, small cell lung cancer tends to recur or relapse within one to two years in the majority of patients, particularly those with extensive stage disease. If the small cell lung cancer 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: Quitting smoking”.)

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/clinicaltrials/learning/

www.cancer.gov/clinicaltrials

file://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.

 

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
Patient information: Non-small cell lung cancer treatment; stage IV cancer
Patient information: Lung cancer risks, symptoms, and diagnosis
Patient information: Quitting smoking

Professional Level Information:

First-line chemotherapy for small cell lung cancer
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
Thoracic radiotherapy in the treatment of limited stage small cell lung cancer
Treatment of refractory and relapsed small cell lung cancer

The following organizations also provide reliable health information.

The National Library of Medicine
(www.nlm.nih.gov/medlineplus/lungcancer.html)

National Cancer Institute
(www.cancernet.nci.nih.gov/)

American Society of Clinical Oncology
(www.cancer.net/portal/site/patient)

Global Resource for Advancing Cancer Education (GRACE)
(www.cancerGRACE.org/lung)

Lung Cancer Alliance
(www.lungcanceralliance.org)

REFERENCES
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.
Aupérin 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.
Slotman B, Faivre-Finn C, Kramer G, et al. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med 2007; 357:664.
Ciombor KK, Rocha Lima CM. Management of small cell lung cancer. Curr Treat Options Oncol 2006; 7:59.
Jackman DM, Johnson BE. Small-cell lung cancer. Lancet 2005; 366:1385.
Lee JJ, Bekele BN, Zhou X, et al. Decision analysis for prophylactic cranial irradiation for patients with small-cell lung cancer. J Clin Oncol 2006; 24:3597.