Overview

A stage IIIB non-small cell lung cancer (NSCLC) has already spread to more than one location in the chest, but cannot be detected outside the chest cavity with currently available diagnostic tests. Unfortunately, most of these patients have undetectable spread of cancer outside the chest. This undetectable cancer is the cause of relapse or recurrence of cancer in the majority of patients. An effective therapy is needed to help improve the cure rates and research is currently ongoing.

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 IIIB non-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.

Optimal treatment of patients with stage IIIB 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.

Combined Modality Treatment

When NSCLC has spread to more than one area in the chest, the cancer cannot be effectively removed with surgery. Historically, most patients with stage IIIB cancers were treated with radiation or with chemotherapy and less than 10% of patients survived 5 years with either treatment approach. Doctors have more recently learned that combining chemotherapy with radiation therapy may improve a patient's survival. The results of a clinical trial comparing sequential chemotherapy and radiation therapy to radiation therapy alone was reported in the early 1990s and demonstrated that patients treated with the sequential approach were almost three times more likely to be alive 5 years from treatment when compared to patients treated with radiation alone. More recently, clinical studies suggest that the concurrent use of chemotherapy and radiation therapy also improves survival compared to radiation alone. These and other clinical trials have established combined modality therapy utilizing both chemotherapy and radiation therapy as a standard treatment approach for patients with stage IIIB cancers.

The results of a recent clinical study conducted in the United States by the Southwest Oncology Group demonstrate that concurrent chemotherapy and radiation followed by further treatment (consolidation) with chemotherapy may improve survival for patients with stage IIIB NSCLC. The study involved 83 patients with stage IIIB NSCLC who received thoracic radiation therapy and concurrent chemotherapy with Platinol® and etoposide followed by three 21-day cycles of Taxotere®. The average survival duration for all patients was 26 months, with 54% of patients surviving two years and 40% of patients still alive at three years. The authors concluded that the addition of Taxotere® consolidation therapy may improve survival for patients with stage IIIB NSCLC compared to concurrent chemotherapy and radiation.

Neoadjuvant Therapy

The practice of administering therapy before surgery is referred to as neoadjuvant. In theory, neoadjuvant therapy can decrease the size of the cancer making it possible to remove with surgery. The major problem with this approach is that more side effects may occur when radiation therapy and/or chemotherapy are administered before surgery.

Administering chemotherapy and radiation therapy together (concurrently) appears to kill more cancer cells than administering them sequentially. Several clinical trials have now demonstrated that neoadjuvant concurrent chemotherapy and radiation therapy can shrink stage IIIB cancers allowing surgical removal of the remaining cancer. The National Cancer Institute sponsored a large clinical trial to formally evaluate neoadjuvant treatment and demonstrated that 4 of 5 patients with stage IIIB NSCLC could have their cancer surgically removed following neoadjuvant chemo-radiotherapy. Patients treated with this approach experienced an overall survival of 22% 6 years from treatment. Unfortunately, approximately 10% of the patients died from side effects of treatment, mostly resulting from complications of surgery. It appears that neoadjuvant therapy may increase the complications of surgery for certain patients.

Chemotherapy as Primary Treatment

Patients with stage IIIB NSCLC who are unable or unwilling to receive radiation therapy can be treated with chemotherapy alone to alleviate the symptoms of their disease and prolong survival time. Over the past several years, chemotherapy has commonly consisted of a two-drug combination containing a platinum-containing compound (Platinol® or Paraplatin®), combined with a second chemotherapy agent. Two-drug combinations have now prolonged the average survival to approximately 8 months, with over 40-50% of patients being alive more than one year from diagnosis. According to a report recently published in the New England Journal of Medicine, the chemotherapy combination regimen of Gemzar®/Platinol® may offer advantages over other standard two-drug regimens.

Researchers from the Eastern Cooperative Oncology Group (ECOG) performed a clinical trial to evaluate several of the newer combination chemotherapy regimens. They enrolled 1,155 persons with advanced NSCLC to receive treatment with one standard chemotherapy regimen, paclitaxel/Platinol®, and compared this regimen to 3 additional chemotherapy combinations: Gemzar®/Platinol®, Taxotere®/Platinol®, and paclitaxel/Paraplatin®. The average duration of patients’ survival was similar for all four treatment regimens and was between 7 and 8 months. The major difference in comparing these 3 chemotherapy regimens was the time to cancer progression. The Gemzar®/Platinol® combination delayed the progression of cancer the longest and produced the best one-year survival rate.

The side effects of treatment were slightly more in the Gemzar®/Platinol® group, and were least severe in the Paraplatin®/paclitaxel group. The Gemzar®/Platinol® regimen was associated with a higher rate of side effects to the bone marrow and kidneys, but had a relatively lower occurrence of fever and infection. The findings from this clinical trial suggest that Gemzar®/Platinol®, Taxotere®/Platinol®, and paclitaxel/Paraplatin® produce similar survival as Platinol®/paclitaxel and should now be considered standard initial treatment. These two-drug regimens provide patients with a number of viable treatment options and certain patients may be candidates for some drugs but not others.

Targeted Therapy 

A targeted therapy is one that is designed to treat only the cancer cells and minimize damage to normal, healthy cells. Cancer treatments that “target” cancer cells may offer the advantage of reduced treatment-related side effects and improved outcomes. 

Conventional cancer treatments, such as chemotherapy and radiation therapy, cannot distinguish between cancer cells and healthy cells. Consequently, healthy cells are commonly damaged in the process of treating the cancer, which results in side effects. Chemotherapy damages rapidly dividing cells, a hallmark trait of cancer cells. In the process, healthy cells that are also rapidly dividing (such as blood cells and the cells lining the mouth and GI tract) are also damaged. Radiation therapy kills some healthy cells that are in the path of the radiation or near the cancer being treated. Newer radiation therapy techniques can reduce, but not eliminate this damage. Treatment-related damage to healthy cells leads to complications of treatment, or side effects. These side effects may be severe, reducing a patient’s quality of life, compromising their ability to receive their full, prescribed treatment, and sometimes, limiting their chance for an optimal outcome from treatment. 

Avastin® (bevacizumab): Avastin is a type of targeted therapy that slows or stops the growth of blood vessels that deliver blood to the cancer, effectively starving the cancer of the oxygen and nutrients it requires to survive and grow. Avastin, in combination with the chemotherapy drugs paclitaxel and carboplatin, is FDA-approved for the treatment of unresectable (not able to be surgically removed), locally advanced, recurrent or metastatic non-squamous, non-small cell lung cancer. The combination of Avastin with paclitaxel and carboplatin has been shown to improve survival compared to chemotherapy alone.[1] 

Treatment of Elderly Patients

The effectiveness of treating elderly patients (over 70 years) with NSCLC is controversial. Since chemotherapy has not been very effective, it has been suggested that no treatment may be better than the toxic side effects of chemotherapy. Some physicians and patients do not elect to use chemotherapy due to their perceived potential intolerance and/or a considered short life expectancy. It is estimated that only 20% of elderly patients with advanced NSCLC ever receive chemotherapy.

Researchers at the Dana-Farber Cancer Institute recently analyzed treatment and outcome data of over 6,000 elderly patients with stage IV NSCLC who were treated with chemotherapy and the results were comparable to those achieved in younger patients with NSCLC treated with chemotherapy. These findings suggest that chemotherapy for advanced NSCLC was as effective in elderly patients as it was in younger patients and there is no reason to deny therapy based solely on age.

Recently, studies have evaluated the chemotherapy drugs, Gemzar®, Taxotere® and Navelbine® separately in the treatment of elderly patients with NSCLC. When used alone as treatment, Gemzar® and Taxotere® produce an overall response rate of approximately 20%, with an average survival of 8 months and are well tolerated by elderly patients. Navelbine®, when used alone has been demonstrated to improve the quality of life for patients and extends survival by approximately 7 weeks versus those receiving only palliative care.

More recent clinical trials have evaluated combinations of Gemzar® and Taxotere® and Gemzar® and Navelbine® as treatment of elderly patients with advanced NSCLC. The combination of Gemzar® and Taxotere® is reported to have a response rate of 29%. The overall response rate for Gemzar® plus Navelbine® is 22% for patients receiving the combination treatment, compared to 15% for patients receiving Navelbine® alone. One year after treatment, the survival rates were 30% for patients receiving Gemzar® plus Navelbine® and 13% for patients receiving Navelbine® alone. The patients receiving combination therapy reported a delay in negative symptoms caused by the cancer and an improved quality of life over those receiving Navelbine® alone. The results from studies indicate that combinations of Gemzar® and Taxotere® and Navelbine® are a well tolerated treatment option for elderly patients with advanced stage NSCLC, and may improve survival time and quality of life.

Strategies to Improve Treatment

While some progress has been made in the treatment of stage IIIB NSCLC, the majority of 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 IIIB NSCLC.

• Strategies to Improve Chemotherapy
  • Chemotherapy prior to chemoradiation
  • Additional chemotherapy after chemoradiation
• Strategies to Improve Radiation Therapy
  • Conformal radiation therapy
• New Approaches to Targeted Therapy
  • Avastin® with Gemzar® and Platinol®
  • Erbitux® (cetuximab)
  • Tarceva® (erlotinib)
• Managing Side Effects
  • Ethyol® (amifostine)

Strategies to Improve Chemotherapy 

Chemotherapy prior to chemoradiation: A course of chemotherapy delivered prior to chemoradiation—sometimes called “induction” chemotherapy—is still being evaluated in clinical trials. Induction chemotherapy that includes the drug Gemzar has been shown to produce promising outcomes. Patients with inoperable stage IIIA or IIIB NSCLC survived 23 months, on average, when treated with Gemzar-based chemotherapy followed by chemoradiation. Nearly three quarters of the patients experienced at least a partial reduction in their cancer following treatment. Nearly half of the patients survived two years or more after treatment.[2] 

Additional chemotherapy after chemoradiation: Administering additional chemotherapy after chemoradiation may produce better outcomes than induction chemotherapy before chemoradiation. In a clinical trial that directly compared these two techniques showed that patients who were treated with chemoradiation first experienced longer survival—approximately 16 months on average, compared to 13 months for patients treated with chemotherapy followed by chemoradiation. However, side effects from treatment side effects of treatment—including inflammation of the throat—were more common among patients who were treated with chemoradiation first.[3] 

Strategies to Improve Radiation Therapy 

Conformal radiation therapy: By using a special computer and CT scan, radiation therapy can be delivered more precisely to the cancer in the lungs. This technique is called 3-dimensional conformal radiation therapy. Precise delivery of radiation therapy directly to the cancer may spare healthy tissue from the side effects of radiation and can allow for higher doses of radiation to be administered, killing more cancer cells. 

In a clinical trial involving patients with stage III NSCLC, conformal radiation administered with chemotherapy produced anti-cancer responses in 75% of the patients. Nearly one quarter of the patients had a complete disappearance of their cancer and half had a partial disappearance. Half of the patients survived one year or more and one quarter survived two years or more.  On average, patients survived one year.[4]

New Approaches to Targeted Therapy 

New Targeted Therapy/Chemotherapy Combinations: The targeted therapy Avastin® (bevacizumab), in combination with the chemotherapy drugs paclitaxel and carboplatin, is FDA-approved for the treatment of unresectable (not able to be surgically removed), locally advanced, recurrent or metastatic non-squamous, NSCLC. 

To explore the effectiveness of combining Avastin with other combination chemotherapy regimens, researchers in Germany recently conducted a phase III clinical trial to assess the addition of Avastin to chemotherapy with Gemzar® (gemcitabine) and Platinol® (cisplatin).[5] The study enrolled patients with previously untreated advanced or recurrent non-squamous NSCLC. Compared to patients treated with Gemzar and Platinol alone, patients treated with Gemzar and Platinol plus Avastin had improved progression-free survival. 

Erbitux® (cetuximab): Erbitux is a type of targeted therapy that inhibits growth of the cancer cell by binding to a portion of the epidermal growth factor receptor (EGFR), a protein located on the surface of many cancer cells, including NSCLC. A phase III clinical trial of patients with stage IIIB or stage IV NSCLC reported that the addition of Erbitux to platinum-based chemotherapy improved overall survival.[6] 

Tarceva® (erlotinib): Tarceva is another drug that inhibits the growth of cancer cells by binding to EGFR.  Tarceva has been shown to improve survival and quality of life in patients with recurrent NSCLC and is FDA-approved for the treatment of these patients.[7] Research is ongoing to determine if initial treatment with Tarceva may provide benefit. 

Managing Side Effects 

Ethyol® (amifostine): Ethyol is a drug that protects some organs from the side effects of radiation therapy, which can make treatment more tolerable and allow for the maximal dose to be administered.  Ethyol is approved by the Food and Drug Administration for use with Platinol and clinical trials are evaluating the use of Ethyol with other chemotherapy drugs. 

The addition of Ethyol to radiochemotherapy has been shown to reduce side effects in the treatment of patients with advanced NSCLC. A direct comparison of treatment with and without Ethyol showed that patients who received Ethyol experienced significantly less inflammation of the esophagus and lung-related side effects. Ethyol did not compromise the effectiveness of treatment.[8] 

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