Friday, February 15, 2008
Malignant mesothelioma. Medical oncology: standards, new trends, trials--the French experience.
Clinical trials investigating new trends in the treatment of stage I and II malignant mesothelioma have shown both intra-pleural immunotherapy and systemic chemo-immunotherapy to be efficacious. Intra-pleural gamma-interferon (gamma-IFN) therapy was associated with tolerable toxicity and an overall response (ORR) rate of 19%, while treatment with intra-pleural recombinant interleukin-2 (IL-2) was more toxic, but yielded an ORR of 47% in phase I trial and 55% in a phase II study. The association of intravenous cisplatin and subcutaneous alpha-interferon (alpha-IFN) was also associated with an encouraging ORR of 40% and a median survival of 12 months. Treatment with cisplatin, alpha-IFN and mitomycin C was associated with moderate toxicity and an ORR of 21% and a median survival of 12 months. The association of cisplatin, alpha-IFN and IL-2 was, however, extremely toxic and resulted in an ORR of 15%. The majority of patients responding to intra-pleural immunotherapy and systemic chemo-immunotherapy had epithelial type mesothelioma. The most encouraging results obtained from trials investigating systemic chemotherapy were following treatment with cisplatin, 5-fluorouracil, mitomycin C and etoposide, where an ORR of 38% and an overall median survival rate of 16 months were achieved. Toxicity was mainly haematological and tolerable.
Mesothelioma: The Basics
What is mesothelial tissue?
The mesothelium is a protective sac that covers and protects most internal organs in the body. It is composed of two layers, one layer covers the organ and the second layer forms a sac around it. The mesothelium produces a lubricating fluid that is released between these layers, allowing moving organs (such as the lungs) to move easily. The area between the two layers is often called the pleural space. Mesothelial tissue is found lining the abdominal cavity organs, the lungs and the heart. What is mesothelioma?
Mesothelioma occurs when the mesothelial cells grow out of control. These cells also lose the ability to stop producing the lubricating fluid when there is enough. This results in organs being encased with a thick rind of tumor tissue and excess fluid build up, causing symptoms. These cells can grow and invade other organs, or spread to other areas of the body. When the cells spread to other areas of the body, it is called metastasis.
The majority of mesotheliomas are found in the lining of the lung. About ten percent of cases are found in the abdominal cavity lining, and even more rarely, mesothelioma is found in the lining of the heart.
Am I at risk for mesothelioma?
Mesothelioma is a rare cancer, with only 2,300 cases diagnosed in 2000, in the United States. It is eight times more common in men, which is due in most part to work-related exposure to asbestos. Risk also increases with age. The biggest risk factor for developing the disease is exposure to asbestos, accounting for 70 to 80 percent of all cases. Asbestos has been used in many products, including cement, brake linings, roof shingles, flooring products, textiles, and insulation. Particles can be released from these products, particularly during the manufacturing process, and inhaled. Prior to knowing the dangers, asbestos miners and other workers exposed to asbestos worked without wearing any protection. Since the 1970's, the U.S. Occupational Safety and Health Administration (OSHA) sets limits for acceptable levels of asbestos exposure and requires protective equipment in the workplace. Family members of people who worked with asbestos were also exposed to the toxin when it was carried home on clothing and hair, putting them at increased risk for mesothelioma. It takes 20 to 40 years from the time of asbestos exposure until mesothelioma is detected. This exposure was usually over a period of time, but has been reported to be as little as one or two months of exposure. Smoking does not seem to increase the risk of developing the disease.
The incidence of mesothelioma in Western Europe is much higher, with 5,000 new cases in 2000. This is because maximal exposure to asbestos in Europe occurred around 1970, whereas the maximum exposure in the U.S. was from the 1930s to 60s. It is expected that rates in the U.S. should begin to decline, whereas rates in Europe are expected to plateau in 2018 before declining.
How can I prevent mesothelioma?
By decreasing exposure to asbestos, the risk of mesothelioma is decreased. Workers who are exposed to asbestos on the job should wear protective clothing and masks. These workers should change their clothing before leaving the work site to avoid carrying any particles home. OSHA has set standards regulating these procedures. What screening tests are available?
There is no good screening test for mesothelioma. Radiologic studies (x-ray, CT scan) are not sensitive enough to detect tumors before symptoms occur.
What are the signs of mesothelioma?
The symptoms of mesothelioma are caused by a build-up of tumor tissue surrounding the lung and fluid in the pleural space that prevents the lung from expanding fully. This causes pressure on the lung, leading to pain and shortness of breath. As the disease progresses, patients may lose weight and have a dry, hacking cough. In the abdomen, this fluid and tumor tissue causes abdominal swelling, pain and weight loss.
How is mesothelioma diagnosed and staged?
Patients who present with symptoms worrisome for mesothelioma may have a chest x-ray done, indicating a build-up of fluid in the lining of the lung. These patients would then undergo CT scan to further evaluate the cancer. In the case of abdominal mesothelioma, a CT scan obtained to visualize the anatomy in the abdomen.
Patients would then undergo a biopsy to have the diagnosis confirmed. In the lung, a thoracoscope is used to go through the chest wall, between the ribs to obtain a sample of the tissue. A peritoneoscope is used to enter the abdomen to obtain a tissue sample in abdominal mesothelioma.
Staging refers to determining the extent of the disease and this dictates the treatment. Physicians use the TNM system (also called tumor - node - metastasis system). This describes the size of the tumor (T), if the lymph nodes are involved (N), and if it has spread to other areas of the body (M). This is then interpreted to a stage between one and four. Patients with earlier stage tumors tend to live longer and respond better to available treatments.
What are the treatments for mesothelioma?
Treatment is dependent on the stage of the disease, the location of the tumor, the patient's age and state of health at the time. Younger, healthy patients, with early stage disease may be candidates for surgery that removes the mesothelial tissue around the tumor. This surgery is extensive and it is not well understood how much benefit it provides the patient.
Traditional radiation therapy has not shown a benefit, and can cause damage to the healthy lung tissue in the process of treating the cancer. Research is investigating ways of giving radiation directly to the tumor, using implants or UV light therapy. Chemotherapy has often been used to treat patients with mesothelioma, but until recently trials did not find any one medication to be superior to others. These medications have had responses in 10 to 20 percent of patients, but combining more than one medication has not increased these rates. Recently, a new medication called pemetrexed (Alimta) was given in combination with cisplatin with positive results. Patients received either cisplatin alone or cisplatin in combination with pemetrexed. Patients who received the combination of drugs had increased response rates, survived longer, and had fewer side effects. This regimen is now considered standard of care for mesothelioma not treatable with surgery. Researchers are conducting studies that administer the chemotherapy directly into the pleural space. So far, the results of these studies have been disappointing.
Because the current therapies have limited effectiveness, researchers are studying new ways to treat mesothelioma. Some of the treatments being investigated include interleukin 2 (a biologic therapy), lovastatin (a cholesterol-lowering drug), immunotherapy, gene therapy (a method that attempts to correct the abnormal gene that causes the cancer to grow out of control), and Photodynamic Therapy (PDT-a treatment that uses a laser to activate a photosensitizing drug during the surgical removal of the cancer). Patients should talk with their physicians about current clinical trials for mesothelioma.
One problem that patients may encounter is the recurring build-up of fluid in the pleural space. This fluid can be removed with a chest tube (a tube that is put into the chest wall and left in for a period of time to allow drainage) or a procedure called thoracentesis (a small needle is put through the chest wall, into the pleural space, the fluid is drained, and the needle removed). In the abdomen, the procedure to remove fluid is called paracentesis. In this procedure, a needle is inserted through the abdomen into the fluid filled space, and the fluid is drained.
If this is a chronic problem, patients may have a catheter placed in the chest semi-permanently, allowing them to drain the fluid themselves at home as they need to. Removal of the fluid alleviates the difficulty breathing and chest pain caused by the build-up.
Follow-up testing?
The physician will follow the patient with physical examinations, chest x-rays, and CT scans.
References
DeVita, V., Hellman, S., & Rosenberg, S. Cancer: Principles and Practice of Oncology, Seventh Edition (2004). Lippincott, Williams & Wilkins, Philadelphia, Pennsylvania.
Light, R. Pleural Diseases, Fourth Edition (2001). Lippincott, Williams & Wilkins, Philadelphia, Pennsylvania.
Vogelzang, N et al., Phase III Study of Pemetrexed in Combination With Cisplatin Versus Cisplatin Alone in Patients With Malignant Pleural Mesothelioma, Journal of Clinical Oncology, 21: 2636-2644 (2003)
National Cancer Institute. Mesothelioma: Questions & Answers
The Mesothelioma Applied Research Foundation : This nonprofit organization’s website is a great resource for patients, families & healthcare professionals.
The mesothelium is a protective sac that covers and protects most internal organs in the body. It is composed of two layers, one layer covers the organ and the second layer forms a sac around it. The mesothelium produces a lubricating fluid that is released between these layers, allowing moving organs (such as the lungs) to move easily. The area between the two layers is often called the pleural space. Mesothelial tissue is found lining the abdominal cavity organs, the lungs and the heart. What is mesothelioma?
Mesothelioma occurs when the mesothelial cells grow out of control. These cells also lose the ability to stop producing the lubricating fluid when there is enough. This results in organs being encased with a thick rind of tumor tissue and excess fluid build up, causing symptoms. These cells can grow and invade other organs, or spread to other areas of the body. When the cells spread to other areas of the body, it is called metastasis.
The majority of mesotheliomas are found in the lining of the lung. About ten percent of cases are found in the abdominal cavity lining, and even more rarely, mesothelioma is found in the lining of the heart.
Am I at risk for mesothelioma?
Mesothelioma is a rare cancer, with only 2,300 cases diagnosed in 2000, in the United States. It is eight times more common in men, which is due in most part to work-related exposure to asbestos. Risk also increases with age. The biggest risk factor for developing the disease is exposure to asbestos, accounting for 70 to 80 percent of all cases. Asbestos has been used in many products, including cement, brake linings, roof shingles, flooring products, textiles, and insulation. Particles can be released from these products, particularly during the manufacturing process, and inhaled. Prior to knowing the dangers, asbestos miners and other workers exposed to asbestos worked without wearing any protection. Since the 1970's, the U.S. Occupational Safety and Health Administration (OSHA) sets limits for acceptable levels of asbestos exposure and requires protective equipment in the workplace. Family members of people who worked with asbestos were also exposed to the toxin when it was carried home on clothing and hair, putting them at increased risk for mesothelioma. It takes 20 to 40 years from the time of asbestos exposure until mesothelioma is detected. This exposure was usually over a period of time, but has been reported to be as little as one or two months of exposure. Smoking does not seem to increase the risk of developing the disease.
The incidence of mesothelioma in Western Europe is much higher, with 5,000 new cases in 2000. This is because maximal exposure to asbestos in Europe occurred around 1970, whereas the maximum exposure in the U.S. was from the 1930s to 60s. It is expected that rates in the U.S. should begin to decline, whereas rates in Europe are expected to plateau in 2018 before declining.
How can I prevent mesothelioma?
By decreasing exposure to asbestos, the risk of mesothelioma is decreased. Workers who are exposed to asbestos on the job should wear protective clothing and masks. These workers should change their clothing before leaving the work site to avoid carrying any particles home. OSHA has set standards regulating these procedures. What screening tests are available?
There is no good screening test for mesothelioma. Radiologic studies (x-ray, CT scan) are not sensitive enough to detect tumors before symptoms occur.
What are the signs of mesothelioma?
The symptoms of mesothelioma are caused by a build-up of tumor tissue surrounding the lung and fluid in the pleural space that prevents the lung from expanding fully. This causes pressure on the lung, leading to pain and shortness of breath. As the disease progresses, patients may lose weight and have a dry, hacking cough. In the abdomen, this fluid and tumor tissue causes abdominal swelling, pain and weight loss.
How is mesothelioma diagnosed and staged?
Patients who present with symptoms worrisome for mesothelioma may have a chest x-ray done, indicating a build-up of fluid in the lining of the lung. These patients would then undergo CT scan to further evaluate the cancer. In the case of abdominal mesothelioma, a CT scan obtained to visualize the anatomy in the abdomen.
Patients would then undergo a biopsy to have the diagnosis confirmed. In the lung, a thoracoscope is used to go through the chest wall, between the ribs to obtain a sample of the tissue. A peritoneoscope is used to enter the abdomen to obtain a tissue sample in abdominal mesothelioma.
Staging refers to determining the extent of the disease and this dictates the treatment. Physicians use the TNM system (also called tumor - node - metastasis system). This describes the size of the tumor (T), if the lymph nodes are involved (N), and if it has spread to other areas of the body (M). This is then interpreted to a stage between one and four. Patients with earlier stage tumors tend to live longer and respond better to available treatments.
What are the treatments for mesothelioma?
Treatment is dependent on the stage of the disease, the location of the tumor, the patient's age and state of health at the time. Younger, healthy patients, with early stage disease may be candidates for surgery that removes the mesothelial tissue around the tumor. This surgery is extensive and it is not well understood how much benefit it provides the patient.
Traditional radiation therapy has not shown a benefit, and can cause damage to the healthy lung tissue in the process of treating the cancer. Research is investigating ways of giving radiation directly to the tumor, using implants or UV light therapy. Chemotherapy has often been used to treat patients with mesothelioma, but until recently trials did not find any one medication to be superior to others. These medications have had responses in 10 to 20 percent of patients, but combining more than one medication has not increased these rates. Recently, a new medication called pemetrexed (Alimta) was given in combination with cisplatin with positive results. Patients received either cisplatin alone or cisplatin in combination with pemetrexed. Patients who received the combination of drugs had increased response rates, survived longer, and had fewer side effects. This regimen is now considered standard of care for mesothelioma not treatable with surgery. Researchers are conducting studies that administer the chemotherapy directly into the pleural space. So far, the results of these studies have been disappointing.
Because the current therapies have limited effectiveness, researchers are studying new ways to treat mesothelioma. Some of the treatments being investigated include interleukin 2 (a biologic therapy), lovastatin (a cholesterol-lowering drug), immunotherapy, gene therapy (a method that attempts to correct the abnormal gene that causes the cancer to grow out of control), and Photodynamic Therapy (PDT-a treatment that uses a laser to activate a photosensitizing drug during the surgical removal of the cancer). Patients should talk with their physicians about current clinical trials for mesothelioma.
One problem that patients may encounter is the recurring build-up of fluid in the pleural space. This fluid can be removed with a chest tube (a tube that is put into the chest wall and left in for a period of time to allow drainage) or a procedure called thoracentesis (a small needle is put through the chest wall, into the pleural space, the fluid is drained, and the needle removed). In the abdomen, the procedure to remove fluid is called paracentesis. In this procedure, a needle is inserted through the abdomen into the fluid filled space, and the fluid is drained.
If this is a chronic problem, patients may have a catheter placed in the chest semi-permanently, allowing them to drain the fluid themselves at home as they need to. Removal of the fluid alleviates the difficulty breathing and chest pain caused by the build-up.
Follow-up testing?
The physician will follow the patient with physical examinations, chest x-rays, and CT scans.
References
DeVita, V., Hellman, S., & Rosenberg, S. Cancer: Principles and Practice of Oncology, Seventh Edition (2004). Lippincott, Williams & Wilkins, Philadelphia, Pennsylvania.
Light, R. Pleural Diseases, Fourth Edition (2001). Lippincott, Williams & Wilkins, Philadelphia, Pennsylvania.
Vogelzang, N et al., Phase III Study of Pemetrexed in Combination With Cisplatin Versus Cisplatin Alone in Patients With Malignant Pleural Mesothelioma, Journal of Clinical Oncology, 21: 2636-2644 (2003)
National Cancer Institute. Mesothelioma: Questions & Answers
The Mesothelioma Applied Research Foundation : This nonprofit organization’s website is a great resource for patients, families & healthcare professionals.
Subscribe to:
Posts (Atom)