Tuesday, May 17, 2011
Bhima Permana Putra
The prognosis for malignant mesothelioma remains disappointing, although there are some modest improvements in the prognosis of new chemotherapy and multimodality treatment. Treatment of malignant mesothelioma in early stages have a better prognosis, but treatment is very rare. Clinical behavior of malignancy is affected by several factors including mesothelial surface of the pleural cavity which continued to favor local metastasis via exfoliated cells, invasion to underlying tissue and other organs in the pleural cavity, and the extremely long latency period between asbestos exposure and the development of the disease. Histological subtype and patient age and health status also help predict prognosis.
1. Operation
Operations, by itself, has proved disappointing. In one large series, median survival with surgery (including extrapleural pneumonectomy) is only 11.7 months. However, research shows varying success when used in combination with radiation and chemotherapy (Duke, 2008). (For more information about multimodality therapy with surgery, see below). A pleurectomy / decortication is the most common operations, in which layers of the chest is removed. Less common is extrapleural pneumonectomy (EPP), in which the lungs, lining the inside of the chest, hemi-diaphragm and the pericardium removed.
2. Radiation
For patients with local disease, and which can tolerate radical surgery, radiation is often given post-operatively as a treatment konsolidatif. The hemi whole-breast treated with radiation therapy, often given concurrently with chemotherapy. The approach using surgery followed by radiation with chemotherapy has been pioneered by a team of breast oncology at Brigham & Women's Hospital in Boston. Delivering radiation and chemotherapy after radical surgery has led to extended life expectancy in selected patient populations with some patients survive more than 5 years. As part of the curative approach to mesothelioma, radiotherapy is also commonly applied to the chest drain sites of insertion, to prevent tumor growth along the chest wall.
Although mesothelioma is generally resistant to curative treatment by radiotherapy alone, palliative treatment regimens are sometimes used to relieve symptoms arising from tumor growth, such as obstruction of major blood vessels. Radiation therapy when given alone with curative intent was never proven to improve survival from mesothelioma. The radiation dose required to treat mesothelioma that has not surgery would be very toxic.
3. Chemotherapy
Chemotherapy is the only treatment for mesothelioma that has been proven to increase survival in randomized and controlled trials. The study, published in 2003 by Vogelzang and colleagues compared cisplatin combination chemotherapy alone with cisplatin and pemetrexed brand name of ALIMTA), chemotherapy (in patients not receiving chemotherapy for malignant pleural mesothelioma who are not candidates earlier and more aggressive curative "surgery". This experiment is the first reported survival benefit from chemotherapy in malignant pleural mesothelioma, showed statistically significant improvement in average survival of 10 months in patients treated with cisplatin alone to 13.3 months in the group of patients treated with cisplatin in combination with pemetrexed and who also received supplementation with folate and vitamin B 12. Vitamin supplements given to patients who are most at trial and pemetrexed-related side effects were significantly less in patients who received pemetrexed when they also received 500mcg of folate daily oral and intramuscular Vitamin B 12 1000mcg every 9 weeks compared with patients receiving pemetrexed without vitamin supplementation. The objective response rate increased from 20% in the cisplatin group to 46% in the combination of pemetrexed. Some side effects such as nausea and vomiting, stomatitis, and diarrhea are more common pemetrexed in combination group but only affects a minority of patients and the overall combination of pemetrexed and cisplatin was well tolerated when patients were receiving vitamin supplements, a good quality of life and lung function tests improved in the combination group pemetrexed. In February 2004, the United States Food and Drug Administration approved pemetrexed for the treatment of malignant pleural mesothelioma. However, there are still unanswered questions about the optimal use of chemotherapy, including when to start treatment, and the optimal number of cycles to give.
Cisplatin in combination with raltitrexed has demonstrated an improvement in survival similar to that reported for pemetrexed in combination with cisplatin, but raltitrexed is no longer available commercially for this indication. For patients unable to tolerate pemetrexed, cisplatin in combination with gemcitabine or vinorelbine is an alternative, or vinorelbine alone, although survival benefit has not been shown for these drugs. For patients who can not be used cisplatin, carboplatin can be replaced but a non-random data have shown lower response rates and high levels of haematological toxicity for carboplatin-based combinations, even with survival rates similar to patients receiving cisplatin.
In January 2009, the United States Food and Drug Administration approved use of conventional therapies such as surgery in combination with radiation and or chemotherapy in stage I or II Mesothelioma after the study was conducted through a national study by Duke University concluded that increased almost 50 points at the level of remission.
4.Imunoterapi
Treatment regimens involving immunotherapy have produced variable results. For example, intrapleural inoculation of Bacillus Calmette-Guérin (BCG) in an effort to enhance the immune response, was found to be of no benefit to the patient (while it may be beneficial for patients with bladder cancer). Mesothelioma cells proved susceptible in vitro lysis by LAK cells following activation by interleukin-2 (IL-2), but patients undergoing this particular therapy experienced major side effects. Indeed, this trial was stopped considering the very high levels of IL-2 toxicity and the severity of side effects such as fever and cachexia. Nonetheless, other trials involving interferon alpha have proved more encouraging with 20% of patients experienced a decrease greater than 50% in tumor mass combined with minimal side effects.
5. Heated Intraoperative intraperitoneal chemotherapy
A procedure known as heated intraoperative intraperitoneal chemotherapy was developed by Paul Sugarbaker at the Washington Cancer Institute. The surgeon held up as much as possible the tumor followed by immediate administration of chemotherapy agent, heated to between 40 and 48 ° C, in the stomach. This fluid diperfusi for 60 to 120 minutes and then drained.
This technique allows administration of high concentrations of selected drugs into the surface of the abdomen and pelvis. Heating the chemotherapy treatment increases the penetration of drugs into the network. Also, heating itself destroy malignant cells over normal cells.
This technique is also used in patients with malignant pleural mesothelioma.
6. Multimodality Therapy
All the standard approach to treating solid tumors, radiation, chemotherapy, and surgery-have been investigated in patients with malignant pleural mesothelioma. Despite surgery, by itself, is not very effective, surgery combined with adjuvant chemotherapy and radiation (trimodality therapy) has resulted in a significant extension of survival (3-14 years) among patients with favorable prognostic factors. Other large series of multimodality treatment, but examination showed only modest improvement in survival (median survival of 14.5 months and only 29.6% surviving 2 years). Substantially reducing the tumor by cytoreductive surgery is the key to prolong survival. Two operations have been developed: extrapleural pneumonectomy and pleurectomy / decortication. Indications for this operation unique. Surgical options depend on the size of tumor patients. This is an important consideration because the volume of tumor was identified as a prognostic factor in mesothelioma. Pleurectomy / decortication spare the underlying lung and is performed in patients with early-stage disease when it is intended to remove all visible tumor gross (macroscopic complete resection), not just palliative. Extrapleural Pneumonectomy is a wider operation involving resection of the parietal and visceral pleurae, underlying lung, ipsilateral diaphragm, and ipsilateral pericardium. This operation is indicated for a subset of patients with more advanced tumors, which can tolerate a pneumonectomy.
1. Operation
Operations, by itself, has proved disappointing. In one large series, median survival with surgery (including extrapleural pneumonectomy) is only 11.7 months. However, research shows varying success when used in combination with radiation and chemotherapy (Duke, 2008). (For more information about multimodality therapy with surgery, see below). A pleurectomy / decortication is the most common operations, in which layers of the chest is removed. Less common is extrapleural pneumonectomy (EPP), in which the lungs, lining the inside of the chest, hemi-diaphragm and the pericardium removed.
2. Radiation
For patients with local disease, and which can tolerate radical surgery, radiation is often given post-operatively as a treatment konsolidatif. The hemi whole-breast treated with radiation therapy, often given concurrently with chemotherapy. The approach using surgery followed by radiation with chemotherapy has been pioneered by a team of breast oncology at Brigham & Women's Hospital in Boston. Delivering radiation and chemotherapy after radical surgery has led to extended life expectancy in selected patient populations with some patients survive more than 5 years. As part of the curative approach to mesothelioma, radiotherapy is also commonly applied to the chest drain sites of insertion, to prevent tumor growth along the chest wall.
Although mesothelioma is generally resistant to curative treatment by radiotherapy alone, palliative treatment regimens are sometimes used to relieve symptoms arising from tumor growth, such as obstruction of major blood vessels. Radiation therapy when given alone with curative intent was never proven to improve survival from mesothelioma. The radiation dose required to treat mesothelioma that has not surgery would be very toxic.
3. Chemotherapy
Chemotherapy is the only treatment for mesothelioma that has been proven to increase survival in randomized and controlled trials. The study, published in 2003 by Vogelzang and colleagues compared cisplatin combination chemotherapy alone with cisplatin and pemetrexed brand name of ALIMTA), chemotherapy (in patients not receiving chemotherapy for malignant pleural mesothelioma who are not candidates earlier and more aggressive curative "surgery". This experiment is the first reported survival benefit from chemotherapy in malignant pleural mesothelioma, showed statistically significant improvement in average survival of 10 months in patients treated with cisplatin alone to 13.3 months in the group of patients treated with cisplatin in combination with pemetrexed and who also received supplementation with folate and vitamin B 12. Vitamin supplements given to patients who are most at trial and pemetrexed-related side effects were significantly less in patients who received pemetrexed when they also received 500mcg of folate daily oral and intramuscular Vitamin B 12 1000mcg every 9 weeks compared with patients receiving pemetrexed without vitamin supplementation. The objective response rate increased from 20% in the cisplatin group to 46% in the combination of pemetrexed. Some side effects such as nausea and vomiting, stomatitis, and diarrhea are more common pemetrexed in combination group but only affects a minority of patients and the overall combination of pemetrexed and cisplatin was well tolerated when patients were receiving vitamin supplements, a good quality of life and lung function tests improved in the combination group pemetrexed. In February 2004, the United States Food and Drug Administration approved pemetrexed for the treatment of malignant pleural mesothelioma. However, there are still unanswered questions about the optimal use of chemotherapy, including when to start treatment, and the optimal number of cycles to give.
Cisplatin in combination with raltitrexed has demonstrated an improvement in survival similar to that reported for pemetrexed in combination with cisplatin, but raltitrexed is no longer available commercially for this indication. For patients unable to tolerate pemetrexed, cisplatin in combination with gemcitabine or vinorelbine is an alternative, or vinorelbine alone, although survival benefit has not been shown for these drugs. For patients who can not be used cisplatin, carboplatin can be replaced but a non-random data have shown lower response rates and high levels of haematological toxicity for carboplatin-based combinations, even with survival rates similar to patients receiving cisplatin.
In January 2009, the United States Food and Drug Administration approved use of conventional therapies such as surgery in combination with radiation and or chemotherapy in stage I or II Mesothelioma after the study was conducted through a national study by Duke University concluded that increased almost 50 points at the level of remission.
4.Imunoterapi
Treatment regimens involving immunotherapy have produced variable results. For example, intrapleural inoculation of Bacillus Calmette-Guérin (BCG) in an effort to enhance the immune response, was found to be of no benefit to the patient (while it may be beneficial for patients with bladder cancer). Mesothelioma cells proved susceptible in vitro lysis by LAK cells following activation by interleukin-2 (IL-2), but patients undergoing this particular therapy experienced major side effects. Indeed, this trial was stopped considering the very high levels of IL-2 toxicity and the severity of side effects such as fever and cachexia. Nonetheless, other trials involving interferon alpha have proved more encouraging with 20% of patients experienced a decrease greater than 50% in tumor mass combined with minimal side effects.
5. Heated Intraoperative intraperitoneal chemotherapy
A procedure known as heated intraoperative intraperitoneal chemotherapy was developed by Paul Sugarbaker at the Washington Cancer Institute. The surgeon held up as much as possible the tumor followed by immediate administration of chemotherapy agent, heated to between 40 and 48 ° C, in the stomach. This fluid diperfusi for 60 to 120 minutes and then drained.
This technique allows administration of high concentrations of selected drugs into the surface of the abdomen and pelvis. Heating the chemotherapy treatment increases the penetration of drugs into the network. Also, heating itself destroy malignant cells over normal cells.
This technique is also used in patients with malignant pleural mesothelioma.
6. Multimodality Therapy
All the standard approach to treating solid tumors, radiation, chemotherapy, and surgery-have been investigated in patients with malignant pleural mesothelioma. Despite surgery, by itself, is not very effective, surgery combined with adjuvant chemotherapy and radiation (trimodality therapy) has resulted in a significant extension of survival (3-14 years) among patients with favorable prognostic factors. Other large series of multimodality treatment, but examination showed only modest improvement in survival (median survival of 14.5 months and only 29.6% surviving 2 years). Substantially reducing the tumor by cytoreductive surgery is the key to prolong survival. Two operations have been developed: extrapleural pneumonectomy and pleurectomy / decortication. Indications for this operation unique. Surgical options depend on the size of tumor patients. This is an important consideration because the volume of tumor was identified as a prognostic factor in mesothelioma. Pleurectomy / decortication spare the underlying lung and is performed in patients with early-stage disease when it is intended to remove all visible tumor gross (macroscopic complete resection), not just palliative. Extrapleural Pneumonectomy is a wider operation involving resection of the parietal and visceral pleurae, underlying lung, ipsilateral diaphragm, and ipsilateral pericardium. This operation is indicated for a subset of patients with more advanced tumors, which can tolerate a pneumonectomy.
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