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The current state of medical science and research cannot explain how and why mesothelioma develops. Whether one asbestos fiber or many are the cause of mesothelioma remains unexplained. What makes one person develop the disease while another does not is likewise a mystery.
There is as yet no known cure for malignant mesothelioma. The prognosis depends on various factors, including the size and stage of the tumor, the extent of the tumor, the cell type, and whether or not the tumor responds to treatment. The individual mesothelioma victimâs age and state of underlying health, as well as their state of mind and motivation to survive the disease likewise may play a role in a favorable prognosis.
Although there is no standard treatment protocol for mesothelioma, numerous treatment options are available for those diagnosed with the disease. Early diagnosis typically results in a greater range of available treatment options. Treatments include:
- traditional chemotherapy
- radiation therapy
- surgery
- experimental therapies and drugs
- complementary medicine and therapies
- lifestyle modifications
A. Traditional Chemotherapy
In traditional chemotherapy, special anti-cancer (cytotoxic) medicines and chemicals are administered, with the goal of killing the malignant cells. Chemotherapy is frequently one facet of a regimen including radical surgery, radiation therapy and/or immunotherapy. Chemotherapy may also be used in situations where the cancer has spread to the extent that surgery is no longer a viable option.
Many drugs have been tried; however all have met with only limited success against malignant mesothelioma. The response rate to single agent chemotherapy is typically less than 20%; use of drug combinations yields little difference in result. There is therefore no standard of systemic chemotherapy for the treatment of mesothelioma.
The chemotherapeutic agents can be administered either systemically (in the blood stream) or intrapleurally (in the pleural cavity itself.) These cytotoxic drugs are very potent. Because they cannot differentiate healthy cells from cancerous ones, they often have many severe side effects.
B. Radiation Therapy (Radiotherapy)
Radiation therapy involves the localized use of high-dose radiation (like x-rays) on malignant tumors. Typically, radiation therapy not used on its own, but rather, in conjunction with other therapies such as surgical resection and chemotherapy. In many instances, the potential benefit that may be gained from radiation is outweighed by The Cause of side effects, including radiation pneumonitis, myelitis, hepatitis and myocarditis, which may significantly diminish the patientâs quality of life. Radiation can also be used for palliative (pain-relieving) purposes--to reduce the tumorâs size, thereby helping to relieve symptoms like pain and shortness of breath.
Factors that can limit the application of radiation as a treatment method include the volume of the tumor and how near it is to vital organs.
Compared to other types of lung cancer in terms of how it responds to radiation, mesothelioma is not as sensitive to radiation as small cell carcinoma of the lung, but may be more responsive to radiation treatment than non-small cell lung cancer.
While there have been anecdotal reports of long term patient survival following high-dose external beam irradiation and intrapleural administration of radioactive isotopes, there have been no studies that replicate these results.
C. Surgery
1. Exploratory surgery
Exploratory surgery of the chest (thoracoscopy or thoracotomy), can be a valuable tool in early diagnosis of mesothelioma. If the disease is detected early, the patient has more treatment options to consider, including the potential for aggressive surgery.
During an exploratory procedure, doctors may also drain built-up fluid from pleural effusions. Drainage may help to alleviate shortness of breath, but is regarded as essentially a palliative measure. Drainage may not be effective, however, where the patient has a bulky tumor in the pleural space or where a thick visceral pleural peel of tumor confines the lung.
2. Surgical treatments
a. Extra-pleural pneumonectomy (EPP)
EPP is regarded as radical surgery. It is a major surgical procedure, involving removal of the pleura, diaphragm, pericardium, portions of the phrenic nerve, and the whole lung affected by the tumor.
To increase the rate of survival, EPP must be followed by adjuvant therapy (chemotherapy and/or radiation), and it carries a significant risk (greater than 15%) of death during or shortly after surgery. Its application is therefore typically confined to a minority of patients who are in Stage I of the disease and who are otherwise medically fit to undergo major surgery.
Typically, EPP is not offered to patients over age 55 or whose disease process has progressed beyond Stage I, due to the generally increased risk of surgery when dealing with an older patient, coupled with the specific risks inherent to EPP.
Given the radical nature of EPP, significant preoperative testing and evaluation are needed. Patients who undergo this procedure should expect to first submit to an MRI of the chest, pulmonary function tests, and echocardiography.
The median survival time following EPP is 16 months, but among patients with epithelial subtype mesothelioma ( a type of mesothelioma affecting part of the lining of the respiratory system), survival time increased to 24 months; those who had epithelial mesothelioma and no involvement of the lymph nodes at the time of surgery demonstrated a significant survival rate of 45% five years post-surgery.
b. Pleurectomy/decortication
Pleurectomy/decortication involves the removal of the pleura÷essentially, surgically stripping the pleura and pericardium from the apex of the lung to the diaphragm--but without removing the entire lung. This procedure offers the best option for locally controlling pleural fluid. The Cause of death is much less than with EPP (under 3%). Pleurectomy is regarded as more effective than talc pleurodesis in reducing the recurrence of pleural effusion associated with mesothelioma.
Pleurecotomy is best used in patients who are managing their disease generally and have good expansion in their lungs, but who have experienced rapid and symptomatic fluid buildup. Pleurectomy may also be a more suitable treatment method for mesothelioma sufferers in later stages of the disease than the more radical and risky EPP, as well as for older mesothelioma sufferers.
Like most of the treatment methods offered for mesothelioma, pleurectomy alone has not been definitively shown to prolong survival. Combined with radiation, however, researchers found a median survival rate of more than 22 months and a 2-year survival rate of 41% in a group of 27 patients primarily suffering from mesothelioma of the epithelial subtype.
Surgery can remove the bulk of the tumor and provide symptomatic relief÷but it is not a viable option if the tumor is near vital organs. Both EPP and pleurectomy/decortication are complex surgeries, not performed frequently by most surgeons, and require referral to centers dedicated to such treatment. Many of these centers also specialize in other forms of mesothelioma treatment, alone or in combination (multi-modal therapy.)
Which type of surgery is recommended depends on many factors, including the stage of the tumor. Notably, in at least one study, researchers found that the size of the tumor prior to surgery was a good predictor of surgical outcome and overall survival. Patients who went into surgery (both types of surgery were considered in the study) with a preoperative tumor volume of less than 100 cubic centimeters had a median survival rate of 22 months÷compared to patients entering surgery with tumors having tumors of more than 100 cc. Their median survival rate was 11 months÷half the time of those who entered surgery with smaller tumors.
Mesothelioma sufferers should evaluate all options carefully, since no one procedure has been comprehensively shown to have distinct advantages over another. Further, surgery has not been shown to offer significant advantages over non-surgical options.
D. New/experimental medications and treatments
1. Experimental drugs
a. Onconase
Onconase, made by pharmaceutical company Alfacell, has shown a survival benefit to sufferers of malignant mesothelioma in a study, the results of which were released in March 1999. The study showed a 34.3% one-year survival rate and 21.1% two-year survival rate to patients with inoperable malignant mesothelioma. Another study of Onconase is expected to compare its results with those of doxorubicin, a standard chemotherapy drug.
Onconase is an enzyme derived from purified frog eggs. The enzyme degrades RNA, which is used by cells to produce protein and energy.
The successful study discussed above monitored 105 mesothelioma patients, all of whom received weekly infusions of Onconase until their cancers failed to respond to the drug. Of these patients, 39% demonstrated either reduction of tumor size or stabilization of the disease, as measured by CT scan. Of this 39%, the mean survival time was over 17 months; 61% of that group survived for a year, and 31.7% survived two years. Even among those with the negative prognostic indicator of abdominal involvement, there was a mean survival rate of 12 months, a 1-year survival rate of 48% and a 2-year survival rate of 35.6%.
One unexplained, but potentially positive finding of the study is that patients with abdominal involvement÷typically a sign that the disease is worsening÷actually had a better outcome than those without abdominal involvement in the disease process.
Patients in this study generally tolerated the drug well, with only five dropping out of the study due to side effects. Typically experienced side effects were kidney problems, swelling of the extremities and rashes.
A 1996 study of Onconaseâs effects on mesothelioma yielded similar results. In that study, 20 patients with malignant mesothelioma were treated with the drug. Three patients demonstrated partial responses÷that is, they showed a greater than 50% reduction in the size of their tumors. Ten patients showed stabilization of the progress of their mesothelioma÷which had been progressing prior to use of Onconase.
b. Lovastatin
Lovastatin, a drug that is typically tolerated well by users, and that has been widely used in the treatment of high cholesterol, has shown positive results in inhibiting mesothelial cell growth. This drug has not yet been subjected to clinical trials, however.
c. Endostatin and angiostatin
Another promising treatment regimen involves endostatin and angiostatin, substances that inhibit the growth of the blood vessels that feed cancerous tumors. Cancers like mesothelioma (as well as breast cancer, melanoma, and kidney cancer) typically need many blood vessels to grow. Use of endostatin and angiostatin inhibits the growth of the blood vessels that feed the tumor, thereby slowing or inhibiting the disease process.
2. Immunotherapy
Immunotherapy is based on the theory that the bodyâs own immune defenses can be mobilized to fight against cancerous cells. Several experimental treatments seek to enhance the immune systemâs ability to combat malignant mesothelioma. These include gene therapy and the use of cytokine proteins such as interferons and interleukin-2. These treatments are being tested both alone and in combination with other treatments such as chemotherapy.
a. Gene therapy
Gene therapy changes the genetic machinery of the cancer cells. The cells are initially infected with "suicide genes," delivered to them by adenoviruses (viruses that cause colds and herpes). The viruses used for gene therapy are disabled and packed with an enzyme, which turns into a poison and cripples the cellâs genetic machinery÷thereby stopping the rapid division of the cancer cells and thus inhibiting rapid growth of the mesothelial tumor. This therapy, which has been successfully used for sufferers of both mesothelioma and brain cancer, may require surgery as well as careful monitoring.
Notably, gene therapy may be better suited to mesothelioma patients than other cancer sufferers. For example, mesothelioma patients are able to tolerate higher doses of the adenoviruses than brain cancer sufferers, and this therapy has not adversely affected the small number of mesothelioma sufferers upon whom it has been implemented. There is no evidence, however, that this therapy reduced the size of mesothelial tumors. Rather, its effect appears to be retardation of tumor growth.
Gene therapy allows for treatment that specifically targets only the tumor. In fact, researchers are studying a vaccine that could be injected directly into the tumor. The specificity of gene therapy in identifying and destroying cancer cells may make it a more attractive option than conventional chemotherapy÷which can indiscriminately kill healthy cells along with cancerous ones.
b. Cytokines ö Interferons and Interleukins
Cytokines are small proteins that are similar to hormones. They have specific effects on the behavior of other cells. Interleuken-2 (IL2), which was initially identified in 1976 and has been used in treatment of AIDS, is one such protein. IL2 stimulates the growth of T-cells. T-cells are a type of immune system cell, sometimes referred to as "killer cells" because they search out and destroy malignant or virally infected cells. Using IL2 as a treatment for pleural mesothelioma is still in the experimental stages, but researchers hope that injecting IL2 intrapleurally will prove to promote a significant anti-tumor response.
To date, however, IL2 and interferon-gamma (IFN-gamma), a similar substance, have produced limited results and substantial adverse effects. IFN-gamma did produce good results when used in a study of 89 patients with early stage mesothelioma. Over 46 months of treatment, there was an overall response rate of 20%. Nine percent of those had complete responses, and an additional ten percent experienced at least a 50% reduction in the size of their tumors. In this study, patients who entered during Stage I of their disease fared the best, reporting a response rate of 45%.
Another immunotherapy agent, IFN-alpha-2a, was found have some limited efficacy÷one complete response and three partial responses÷in a group of 25 patients who received the agent subcutaneously. IFN-alpha-2a did not produce significant side effects in that study.
Finally, significant regression of mesothelioma has been reported from direct injection of the immunotherapy agent GM-CSF into the tumor on a regular basis.
3. Photodynamic therapy
Photodynamic therapy uses light to kill cancerous cells. The patient receives a photosensitizing drug-- which targets cancer cells and renders them vulnerable to light of specific wavelengths. After the drug has sensitized the cancerous cells, fiberoptic cables are placed in the body (usually through open-chest surgery). The fiberoptic cables direct light of a precisely adjusted frequency onto the tumor. This causes the photosensitizing drug to produce a toxic oxygen molecule, which kills the cancer cell.
Patients who undergo this type of therapy often do so following surgery and chemotherapy.
Although this treatment is still in a very experimental stage for the treatment of mesothelioma, it has shown promising results in the treatment of other cancers.
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