Patients with limited disease small cell lung cancer have cancer that is confined to a single location in the chest that is not detectable outside the lung. Patients with this type of cancer are potentially curable.
A variety of factors ultimately influence a patient’s decision to receive treatment of cancer. The purpose of receiving cancer treatment may be to improve symptoms through local control of the cancer, increase a patient’s chance of cure, or prolong a patient’s survival. The potential benefits of receiving cancer treatment must be carefully balanced with the potential risks of receiving cancer treatment.
The following is a general overview of the treatment of limited small cell lung cancer. Circumstances unique to your situation and prognostic factors of your cancer may ultimately influence how these general treatment principles are applied. The information on this Web site is intended to help educate you about your treatment options and to facilitate a mutual or shared decision-making process with your treating cancer physician.
Most new treatments are developed in clinical trials. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Participation in a clinical trial may offer access to better treatments and advance the existing knowledge about treatment of this cancer. Clinical trials are available for most stages of cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. To ensure that you are receiving the optimal treatment of your cancer, it is important to stay informed and follow the cancer news in order to learn about new treatments and the results of clinical trials.
Before the routine use of chemotherapy, the average patient with limited stage small cell lung cancer was treated with radiation therapy and lived approximately 3 months. Since the cancer usually recurred both within and outside the lungs, fewer than 5% of patients survived over 5 years. Radiation therapy was not an effective form of treatment; however, it was proven to be better than surgical removal. Radiation and surgery are local treatments because they target cancer cells at the site of occurrence. Chemotherapy differs from radiation therapy and surgery because it is a systemic treatment, meaning that it attacks cancer cells everywhere in the body. Small cell lung cancer cells are very responsive to chemotherapy. By the mid to late 1980s, combination chemotherapy treatment with etoposide and Platinol®, often in combination with radiation therapy, appeared to completely eradicate the cancer in 40-60% of patients. Unfortunately, the cancer typically recurred in most patients, but the average patient’s survival improved to 14 months and 20% of patients survived over 5 years.
During the 1980s, the results from several small clinical trials indicated that combining radiation and chemotherapy could further improve a patients chance of survival. As a result, a multi-modality treatment approach using radiation in combination with chemotherapy was adopted. A large clinical trial sponsored by the government of Canada compared radiation therapy administered concurrently with either the 2nd or 6th cycle of chemotherapy. Patients treated with chemo-radiotherapy during the 2nd cycle were almost twice as likely to survive 5 years compared with patients treated during the 6th cycle. Although the practice of delivering radiation therapy early in the chemotherapy sequence has become relatively standard, researchers continue to explore different chemotherapy drugs and methods of delivering radiation therapy. Results from a large clinical trial sponsored by the National Cancer Institute (NCI) in 1996 indicated that 31% of patients with limited disease small cell lung cancer who were treated with concurrent Platinol® and etoposide chemotherapy and radiation now survive longer than 3 years.
Surgery has a very minor role in the treatment of small cell lung cancer because the cancer has typically already spread throughout the body at the time of initial diagnosis. However, some patients have a single small area of cancer at diagnosis. These single small cancer lesions are referred to as a “solitary pulmonary nodules.” Surgical removal of these cancers, followed by treatment with adjuvant chemotherapy with or without radiation, results in 5-year survival rates in excess of 50%.
Approximately 10% of patients with small cell lung cancer will have involvement of the brain at the time of initial diagnosis. Additionally, up to 50% of patients receiving treatment will have the cancer relapse in the brain within 2 years of initial diagnosis. This is because they had micrometastases that were not initially detected by a brain scan. For this reason, the practice of delivering radiation therapy to the brain for the purpose of preventing relapse has been widely utilized. This “prophylactic” use of radiation decreases the risk of relapse, but has not markedly improved the overall survival of patients. Therefore, the practice of administering prophylactic brain radiation has been adopted for patients who achieve an initial substantial response to chemo-radiotherapy of their cancer.
Strategies to Improve Treatment
While some progress has been made in the treatment of limited small cell lung cancer, better treatment strategies are needed, as many patients still experience disease recurrence. The progress that has been made in the treatment of small cell lung cancer has resulted from development of multi-modality treatments and participation in clinical trials. Future progress in the treatment of small cell lung cancer will result from continued participation in appropriate clinical trials. There are several areas of active exploration aimed at improving the treatment of small cell lung cancer.
Supportive Care: Supportive care refers to treatments designed to prevent and control the side effects of cancer and its treatment. Side effects not only cause patients discomfort, but also may prevent the optimal delivery of therapy at its planned dose and schedule. In order to achieve optimal outcomes from treatment and improve quality of life, it is imperative that side effects resulting from cancer and its treatment are appropriately managed. For more information, go to Supportive Care.
New Combination Chemotherapy Regimens: Recently, a combination of Camptosar® and Platinol® chemotherapy demonstrated improved survival in patients with extensive small cell lung cancer when compared with the previous “standard regimen” of Platinol® and etoposide. Clinical trials are ongoing to evaluate Camptosar® combined with Platinol® and other anti-cancer therapies to improve the treatment of limited stage disease. In addition to Camptosar®, other chemotherapy agents, including paclitaxel and Ifex®, have also been combined with etoposide and platinum compounds, producing 3-drug regimens. These 3-drug regimens can be administered safely, produce higher response rates and may improve survival rates compared to previous 2-drug regimens.
High-Dose Chemotherapy: High-doses of chemotherapy are more effective at killing cancer cells than lower doses. However, high-dose chemotherapy (HDC) destroys many other cells in the body, including stem cells. Stem cells are immature blood cells produced in the bone marrow which mature into either red blood cells, which carry oxygen to tissues; white blood cells, which fight infection; and platelets, which aid the blood in clotting. A stem cell transplant (SCT) is a procedure that replaces the stem cells that are destroyed by high-dose chemotherapy and/or radiation therapy with healthy stem cells. There are two main types of stem cell transplants. Autologous stem cell transplants use a patient’s own stem cells, which are collected prior to the high-dose treatment and then re-infused after the treatment. Allogeneic stem cell transplants use stem cells collected from the blood or bone marrow of a related or unrelated donor.
Early attempts at using very high doses of chemotherapy and bone marrow transplant produced high cancer response rates, but the treatment was associated with significant side effects. In the 1990s, several technologic advances have made high-dose chemotherapy safer and easier to deliver. Two studies have indicated that high-dose chemotherapy and autologous stem cell transplant improve progression-free survival and overall survival in patients with limited disease SCLC. In one of these studies, doctors from Harvard University used HDC and autologous SCT to treat patients who had achieved a partial disappearance of cancer after standard chemotherapy treatment. Five years following treatment, 41% of patients survived. Of the patients who achieved a complete or near-complete remission prior to receiving HDC, 53% were alive without evidence of cancer recurrence five years from treatment. The other, more recent, study was conducted in Switzerland and involved 18 patients with limited disease SCLC who received HDC and autologous SCT. Fourteen patients in the study were able to complete the intensive therapy. The total anti-cancer response rate was 95%. Two years following treatment, 55% of patients had no progression of cancer and the overall survival was 65%. The average progression-free survival was 29 months and the average overall survival has not yet been reached.
Recent studies have also indicated that higher initial doses of chemotherapy appear to improve long-term survival rates in patients with limited SCLC. The New England Journal of Medicine recently published long-term follow-up data from one study that compared higher and lower initial doses of chemotherapy. This clinical trial involved 105 patients who received either higher or lower doses of the chemotherapy agents Platinol® or cyclophosphamide. The results of the trial indicated that patients who received higher doses of chemotherapy had improved survival compared to patients who received lower doses. The researchers who conducted this clinical trial recently re-evaluated these patients after an average follow-up period of 11 years to determine if the survival benefits of the higher doses of chemotherapy persisted. Two years following treatment, 42% of the patients who had received higher doses of chemotherapy were still alive, compared to only 20% of the patients who had received the lower doses. Similarly, five years following treatment, 26% of the patients who had received higher doses were alive, compared to only 8% of patients who had received lower doses. Although the survival benefits of the higher dose chemotherapy declined over time, survival was still highest 10 years following therapy in the patients who had received the higher doses of chemotherapy.
The results of these studies suggest that higher initial doses of chemotherapy appears to improve long-term survival rates in patients with limited SCLC. These results emphasize the importance of maintaining dose intensity, indicating that dose reduction due to side effects may hinder achievement of optimal outcomes. To learn more about high-dose chemotherapy and stem cell transplant, go to Stem Cell Transplant.
Biologic Therapy: Following cancer treatment with chemotherapy, patients often achieve a complete remission (disappearance of detectable cancer). Unfortunately, many patients in remission will later experience a relapse of their cancer. This is because not all of the cancer cells were destroyed. Doctors refer to this as a state of “minimal residual disease”. Many doctors believe that applying additional cancer treatments when only a few cancer cells remain represents the best opportunity to prevent the cancer from returning. Biologic agents that work in various ways to stimulate the immune system are being evaluated to prevent or delay relapses. Examples of biologic agents that can be used to treat minimal residual cancer include cytokines, vaccines and monoclonal antibodies. Large multi-institutional and several smaller clinical trials are ongoing to evaluate these new approaches.
Gene Therapy: Currently, there are no gene therapies approved for the treatment of lung cancer. Gene therapy is defined as the transfer of new genetic material into a cell for therapeutic benefit. This can be accomplished by replacing or inactivating a dysfunctional gene or replacing or adding a functional gene into a cell to make it function normally. Gene therapy has been directed towards the control of rapid growth of cancer cells, control of cancer death or efforts to make the immune system kill cancer cells. A few gene therapy studies are being carried out in patients with refractory lung cancer. If successful, these therapies could be applied to patients with earlier stage disease.
Photodynamic Therapy: Currently, photodynamic therapy is in clinical trials for patients with limited SCLC whose cancer is causing an endobronchial obstruction. Photodynamic therapy works through the use of a photosensitizing agent and light. The photosensitizing agent is typically comprised of a porphyrin, which is a naturally occurring substance in the body involved in a variety of biological processes. The photosensitizing agent is injected into a patient’s vein a couple of hours prior to surgery. During this time, the agent selectively collects in rapidly growing cells such as cancer cells. During surgery, the physician applies a certain wavelength of light through a hand held wand directly to the site of the cancer and surrounding tissues. The energy from the light activates the photosensitizing agent, causing the production of a toxin that accumulates in the cancer cells and ultimately destroys them.