Stage II Non-Small Cell Lung Cancer

Overview

A stage II non-small cell lung cancer is located in one lung and may involve lymph nodes on the same side of the chest that do not include lymph nodes in the mediastinum.

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 stage II NSCLC. 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.

For patients diagnosed with a stage II NSCLC, the mainstay of treatment is surgical removal of the cancer. The initial objective of physicians is to determine whether the cancer can be removed surgically and how well surgery will be tolerated. In general, surgical removal of stage II cancers results in over 25-35% of patients being alive without evidence of their cancer recurring within 5 years of treatment. Other factors, such as the size and specific location of the cancer may improve or diminish the chance of cure.

Surgical removal of the cancer may be accomplished by removing the entire lung (pneumonectomy), a lobe of the lung (lobectomy) or even a small segment of the lung (segmentectomy). In general, the less lung that is removed, the greater the preservation of lung function and the lower the risk of major side effects from the procedure. On the other hand, if too little lung is removed, there is an increased chance of a local cancer recurrence. Currently, most physicians recommend a lobectomy. A patient’s general overall condition, age and location of the cancer are other factors that may influence the type of surgery performed and the side effects associated with the surgery. Patients should carefully discuss the risks and benefits of their situation with their surgeon prior to removal of the cancer.

Optimal treatment of patients with stage II lung cancer often requires more than one therapeutic approach. Thus, it may be important for patients to be treated at a medical center that can offer multi-modality treatment involving medical oncologists, radiation oncologists, surgeons and specialists in pulmonary medicine.

Neoadjuvant Therapy

It is important to realize that many patients with stage II disease already have small amounts of cancer outside the chest upon diagnosis that cannot be detected with any of the currently available tests. Undetectable areas of cancer outside the chest are referred to as micrometastases. The presence of micrometastases causes the relapses that follow treatment with surgery alone. An effective treatment is needed to cleanse the body of micrometastases in order to improve the approximate 30% cure rate achieved with surgical removal of the cancer. Efforts are currently underway to find such a therapy.

Neoadjuvant therapy is treatment delivered before surgical removal of the cancer. Neoadjuvant therapy has the potential advantage of immediately delivering treatment, thereby ensuring that therapy is delivered to any cancer cells that may have spread outside the chest. Neoadjuvant therapy may also decrease the size of the primary cancer, thereby allowing more complete surgical removal of the cancer. In May of 1999, doctors from France reported the results of a clinical study directly comparing surgery to neoadjuvant chemotherapy and surgery. Radiation therapy was also used following surgery in patients with large cancers or those involving lymph nodes.

In this clinical study, 11% of patients treated with neoadjuvant chemotherapy had complete disappearance of their cancer confirmed at surgery. Patients treated with neoadjuvant chemotherapy experienced more side effects following surgery than patients treated with surgery alone; however, they survived longer and were less likely to experience cancer recurrence. This clinical study demonstrated a benefit to neoadjuvant (preoperative) chemotherapy and stands in contrast to trials of adjuvant (postoperative) chemotherapy studies, which have not shown improvement in survival when compared to surgery alone. It may be that delaying chemotherapy treatment until after surgery is detrimental. Moreover, as many as one-third of patients in studies evaluating adjuvant chemotherapy are never treated because of side effects from their surgery or cancer.

Combined Neoadjuvant and Adjuvant Chemotherapy

Some doctors have advocated combining both adjuvant and neoadjuvant chemotherapy to reduce the risk of cancer recurrence. Researchers from several medical centers evaluated the use of a new neoadjuvant chemotherapy combination and reported the results in March 2000. They treated 94 patients with stage I to IIIA NSCLC with a chemotherapy combination of paclitaxel and Paraplatin®, followed by surgery to remove the cancer. Those who had complete responses after surgery also received 3 additional cycles of chemotherapy. After the patients received the initial chemotherapy, 56% had a major response and 94% underwent subsequent surgery. Eighty-six percent had complete surgical removal of all visible cancer. After one year, 85% of the patients survived. Longer follow-up and additional studies to directly compare this regimen with surgery alone will be necessary to determine the true effectiveness of combined neoadjuvant and adjuvant chemotherapy treatment.

Over the past several years, other new chemotherapy drugs have been discovered that are more active at destroying lung cancer cells. It may be that these newer chemotherapy drugs administered before surgical removal of stage I NSCLC will further improve patient outcomes or will provide benefit when administered following surgery. Patients with stage I to IIIA NSCLC may wish to talk with their doctor about the risks and benefits of receiving chemotherapy before surgery or of participating in a clinical trial in which new treatments are being studied.

Strategies to Improve Treatment

While some progress has been made in the treatment of stage II NSCLC, many patients still experience disease recurrence and better treatment strategies are needed. The progress that has been made in the treatment of NSCLC has resulted from improved pre-treatment staging of the cancer, development of multi-modality treatments and participation in clinical trials. Future progress in the treatment of NSCLC will result from continued participation in appropriate clinical trials. Currently, there are several areas of active exploration aimed at improving the treatment of stage II NSCLC.

New Neoadjuvant Chemotherapy Regimens: Current clinical trials are focusing on combining chemotherapy drugs known to be active in NSCLC, such as Gemzar®, Taxotere®, paclitaxel, Paraplatin® and Platinol® into treatment regimens in order to further improve survival duration and decrease the side effects of neoadjuvant therapy.

Adjuvant Therapy: Surgery is the cornerstone of treatment for the management of stage II NSCLC for patients who have surgically removable cancers. Adjuvant therapy is the delivery of treatment following surgery. Radiation therapy and chemotherapy administered following surgical removal of the cancer are two types of adjuvant therapy that doctors have used in attempts to further decrease the chance of a local cancer recurrence. Clinical trials evaluating adjuvant chemotherapy are currently ongoing.

Management of Anemia in NSCLC:
Anemia is a term that refers to low levels of circulating red blood cells (RBCs) in the blood. Red blood cells are responsible for delivering oxygen to tissues throughout the entire body. Bone marrow is stimulated to produce RBCs by a chemical substance called erythropoietin, which is secreted by the kidneys. Cancer patients, particularly those receiving chemotherapy, often suffer from anemia. Common symptoms caused by anemia include severe fatigue, shortness of breath, greatly diminished activity levels and a reduced overall feeling of well-being. Severe anemia often necessitates blood transfusions, which have associated risks of infection, intolerance and increased medical costs. In addition, anemia can delay the administration of treatment or cause dose reductions, impeding optimal treatment benefits.

Erythropoietin can be manufactured outside the body and administered to patients. Recombinant human erythropoietin (rHuEPO), a commonly used drug for cancer patients receiving treatment, is comprised of manufactured erythropoietin. It has been shown to reduce the severity of anemia and reduce symptoms of fatigue in patients by stimulating the bone marrow to produce more RBCs. rHuEPO is administered daily or three times a week for the treatment of chemotherapy induced anemia.

Recently, researchers have developed Aranesp®, a new form of erythropoietin that stimulates production of RBCs in the same manner as erythropoietin, and may only need to be administered once every two to three weeks. This allows for less frequent dosing while maintaining benefits of the medication. In essence, patients may be able to avoid several trips to the physician and receive fewer subcutaneous injections.

A recent clinical study evaluating the use of ARANESP involved over 300 patients with lung cancer who were being treated with chemotherapy. Half of the patients received Aranesp® once every three weeks during treatment and the other half received a placebo. Patients receiving Aranesp® had a significantly lower incidence and/or severity of anemia compared to those receiving placebo. Only 21% of patients receiving Aranesp® required a blood transfusion during treatment, compared with 51% of patients receiving placebo. The average number of hospitalization days during treatment was 13.5 for patients receiving Aranesp® and 17.7 for patients receiving placebo. Additionally, patients receiving Aranesp® reported a higher quality of life compared to those receiving placebo.

These results indicate that Aranesp® reduces the severity and incidence of anemia in lung cancer patients receiving chemotherapy, ultimately reducing blood transfusions, allowing optimal treatment schedules and enhancing a patient’s quality of life.

Cryotherapy: Cryotherapy is a new treatment procedure that is still in investigative stages for various cancers. Cryotherapy is a technique that kills cancer cells by freezing them with sub-zero temperatures. During this procedure, hollow steel probes are placed inside and surrounding the cancer. Liquid nitrogen is then circulated through the probes, freezing the cancer cells and creating a ball of ice that surrounds the cancer. Once an adequate ice ball is formed, heated nitrogen is circulated through the probes. This process is then repeated.

Recently, researchers from France conducted a clinical trial evaluating cryotherapy for the treatment of early stage lung cancer. Cryotherapy was performed through a rigid bronchoscope (a lighted tube that is placed into the bronchi). In this trial, 35 patients with early stage lung cancer received cryotherapy, 20% of whom had multiple locations of early stage lung cancer. One year following treatment, 91% of patients had a complete disappearance of cancer. Four years following treatment, only 10 patients experienced a local cancer recurrence. The treatment was well tolerated by these patients. These results are promising for patients with ESBC, as treatment with surgery is often associated with side effects.

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 advanced lung cancer. If successful, this therapy could be applied to patients with earlier stage disease.