Treatment Options
Chemotherapy & Radiation
How chemotherapy works
Chemotherapy, the use of powerful, frequently toxic medications to attack a tumor, works because tumor cells are growing more rapidly than any other cells in the body. Because of their rapid growth they absorb substances in the bloodstream, more rapidly than other tissues, and they are more vulnerable to chemicals that interfere with or kill rapidly growing cells. The medications used in chemotherapy disrupt cell reproduction by a variety of methods.
Chemotherapy is most often delivered into the bloodstream either by injection, or through an IV line, dissolved in a saline solution. These methods of delivery, called systemic administration, means that the medication travels everywhere the circulatory system goes, and all tissues are exposed to the toxic chemicals. In most treatment for mesothelioma, chemotherapy is administered in a series of closely-spaced treatments, with periods of recuperation in between the series.
Because of their toxicity, it is essential that the chemotherapeutic agents clear the body as rapidly as possible, to reduce the impact on healthy tissues. Because the kidneys play a central role collecting and excreting toxic chemicals, treatment planning for chemotherapy involves a careful assessment of kidney function. Healthy kidneys are a requirement if chemotherapy is to be used.
Healthy organs such as the brain, the kidneys, the heart, which are not involved in the cancer, are exposed to the toxic medications, and may suffer tissue damage. Antidotes to the chemotherapy are often administered to protect the rest of the body from its effects. The fastest growing normal cells in the body, red and white blood cells and sperm cells, also absorb the medication at higher rates, and are vulnerable to damage. Side effects from chemotherapy are a consequence of other tissues' absorption of the medication.
System-wide absorption of chemotherapy medications and severe side effects has long been a concern of physicians and researchers. More recently, oncologists have developed targeted chemotherapy, methods for delivering the toxic medications only to the area of the body where the tumor is. Researchers are developing methods to target medications only to certain cell types.
Localized administration targets the specific area of the body where the tumor is. When the chemotherapy drugs are delivered directly to the tumor, higher doses can be used. Heated chemoperfusion, in which chemotherapy chemicals heated to between 40 and 48°C (104-118°F) are perfused directly into the chest cavity or abdomen in the operating room after the tumor has been debulked is an example of localized administration. Another approach used with pleural mesothelioma is to create a shunt, a specialized tube, through which chemotherapy drugs can be injected into the chest cavity. These methods allow much higher doses of chemicals to be used because most of the drug is directed only at the tumor, and very little of it enters the bloodstream.
A very promising area of research is the synthesis of chemical agents with molecular structures that attach only to specific types of cells. A drug would be crafted that would attach only to a specific type of cancer cell. Such a drug could circulate through the rest of the body without harming other tissues, because it would attach only to the receptor sites of the cancer cells. This kind of highly targeted drug is not yet in general use, but clinical trials are testing such drugs' safety and effectiveness.
Risks and side effects of chemotherapy
Because the chemical agents used in chemotherapy are toxic, healthy organs and systems are affected. One of the most vulnerable areas is the bone marrow, where white cells are produced.
Many patients experience low white and red cell counts, and reduced platelets. Immune suppression, brought about by the reduced white cell count is a very frequent side effect of chemotherapy. There are drugs which can increase the production of red cells, platelets, and of white cells. During the time when the immune system is compromised, the patient is more vulnerable to disease and infection. Vaccines for flu and pneumonia should be up to date before chemotherapy starts, and exposure to infection minimized.
Nausea and vomiting, fatigue, and changes in taste and smell are frequent side effects of chemotherapy. Medications are available which can reduce the impact of these symptoms. Patients considering chemotherapy should talk with their doctors about possible side effects and the plan for managing them.
New Treatment Approaches
New drugs
Conventional chemotherapy drugs have not proven effective against advanced mesothelioma. Now, several new approaches to cancer treatment are being studied. These include anti-angiogenesis drugs (which kill cancers by preventing the growth of blood vessels that supply the tumor with nourishment) such as Bevacizumab (Avastin) and anti-growth factor drugs (which interfere with substances some cancer cells produce to stimulate their own growth) such as Erlotinib (Tarceva).
Ranpirnase (Onconase) is an enzyme that breaks down RNA. Preliminary studies show thiat it has helped some patients with mesothelioma to live longer; larger trials are under way. Another new drug being tested in mesothelioma clinical trials is suberoylanilide hydroxamic acid [SAHA], also called Vorinostat, which may reduce growth of mesothelioma cells by inhibiting an enzyme that controls certain proteins called histones, which regulate DNA.
Multimodality therapy
Treatments that use various combinations of surgery, radiation therapy, and chemotherapy, called multimodality therapy, are increasingly the standard for treatment of mesothelioma.
Gene TherapyA new approach being tested for mesothelioma on mesothelioma is gene therapy, in which specially modified viruses is injected into the pleural space, where it infects the mesothelioma cells. When this infection occurs, the virus injects a gene into the mesothelioma for interferon-beta, an immune system hormone (cytokine) that may help activate immune system cells to attack the cancer.
Radiation
For both pleural and peritoneal mesotheliomas, radiation is frequently used at the site of a surgical incision to prevent malignant seeding. Radiation has also been used in the chest cavity after an extrapleural pneumonectomy, to reduce the recurrence of tumor growth.
Like chemotherapy, radiation damages healthy tissue as well as cancerous tissue. The field of interventional radiation machines is evolving rapidly; there are now machines which utilize the imaging precision of computerized tomography to enable the radiologist to target a tumor and a very small area around it. As this precision targeting improves, radiation may be used more widely as an adjuvant therapy.
