New drug may be added to the fight against mesothelioma
The medical journal Cancer, Chemotherapy and Pharmacology has published a report of Japanese researchers testing new drug, S-1, for possible use against pleural mesothelioma. Although it is a rare cancer, mesothelioma has no cure and is estimated to cause fifteen to twenty thousand deaths each year around the world.
Mesothelioma is caused by toxic chemical asbestos, which continues to be used around the world in building and construction. Many countries, including the US have all but discontinued asbestos use and enforce strict regulations pertaining to its use and removal.
With a typical latency period ranging from twenty to fifty years, mesothelioma cases will continue to rise until asbestos use has been totally discontinued for decades. The World Health Organization estimates an approaching ninety-thousand mesothelioma cases annually if asbestos use patterns are not drastically changed. With no known mesothelioma cure, new treatments are welcomed by mesothelioma victims and their families.
S-1 is an anti-tumor drug used on gastric cancer in Japan, Korea, China and other Asian countries. Although is it currently not available for use in the US, S-1 has been recommended for approval to treat gastric cancer in Europe. Developed by Taiho Pharmaceutical Company, S-1 is known by its brand name Teysuno.
Current mesothelioma treatments consist of surgery, chemotherapy, radiation therapy and palliative treatments for patients choosing to focus on quality of life rather than cancer-direct treatments. Mesothelioma is often diagnosed quite late in its development; life expectancy following diagnosis is short, ranging from six months to five years. Mesothelioma is characterized by irregularly patterned tumors throughout the lung lining and lining of other abdominal cavities. Pleural mesothelioma is specifically the cancer in lung lining, while peritoneal mesothelioma refers to the same cancer affecting linings of other abdominal cavities. Although both are rare cancers, pleural mesothelioma is the more common of the two.
S-1 was developed to prevent cancer tumor growth as well as to support another anti-cancer medication, 5-FU. In the study of S-1, lab mice received mesothelioma cells in their chest cavities, which were allowed to develop for quite some time before test treatments. This wait was to simulate the typical late stage at which human mesothelioma patients began treatments. It was reported that the mice responded well to S-1, which reduced their cancer growth and prolonged their survival times.
Researchers of the study concluded that S-1 is promising as a possible good drug to use against pleural mesothelioma.
Mesothelioma patient beats the odds
Each year about three thousand Americans suffer from mesothelioma, a rare and aggressive cancer that has no known curative treatments. Mesothelioma develops in the mesothelium, the lining of the lungs and abdominal cavities. It is caused almost solely by exposure to the toxic fibers of asbestos. After asbestos exposure, mesothelioma can take decades to develop into recognizable signs and symptoms, usually being diagnosed between middle and old age. Once diagnosed, patients’ life expectancy averages eighteen months.
Today, there is one woman who is not telling this short and painful story. Karen Grant was diagnosed with mesothelioma at age 29. Years younger than the usual mesothelioma patient, Grant was beating odds from the beginning of her case. For treatment, Grant turned to Dr. David J. Sugarbaker of the Mesothelioma Program at Brigham and Women’s Hospital in Boston. Dr. Sugarbaker was chief of the hospitals Division of Thoracic Surgery as well as a Wilson Professor of Oncologic Surgery at Harvard Medical School.
Grant underwent many of the most recent trends in mesothelioma treatment. Two extrapleural pneumonectomies were performed on her lungs to rid the organs of cancerous tumors and infected tissues. These operations were followed by laser surgery to kill remaining cancer cells that could not be removed during the extrapleural pneumonectomies.
After all surgeries were completed, Dr. Sugarbaker and his staff administered chemotherapy baths to both of Grants lungs. The drug was heated to a temperature proven more potent on cancer cells and then used to bath the infected areas. This was followed by additional rehabilitative therapies.
Five years later, Grant is now in her mid-thirties with no signs of cancer. Dr. Sugarbaker’s great success may be in part due to Grant’s age—her entire ordeal from diagnosis through treatment was completed at an age at least twenty years younger than most mesothelioma patients. However, Dr. Pasi Janne of the Dana-Farber Institute has called Dr. Sugarbaker’s treatment “a milestone” in the path toward finding a cure for mesothelioma.
Dr. Sugarbaker and his staff continue to research treatments for mesothelioma, knowing this one great success stands against thousands of mesothelioma deaths. Grant’s recovery could be the inspiration needed for the medical community diligently closing the gap between new research and the growing patient population.
Mesothelioma drug raltitrexed proves promising
Raltitrexed is being hailed as a beneficial drug when administered in combination with cisplatin for the treatment of mesothelioma. Created by AstraZeneca, raltitrexed is an antimetabolite, a chemical that stops the growth and division of cells. Fast cell growth and division characterizes many cancers, including malignant mesothelioma.
Mesothelioma is an aggressive cancer of the lung lining caused by asbestos fibers. Although it is a comparatively rare cancer, thousands of Americans suffer from it each year. As asbestos continues to be used around the world, the number of mesothelioma cases is expected to rise. Prognoses include a painful and short survival time, often not
exceeding eighteen months.
Mesothelioma patients in clinical trials respond well to raltitrexed when used in conjunction with cisplatin, the typical chemotherapy treatment in mesothelioma patients. While cisplatin works to bind itself to the cells and DNA of cancer tumors causing the cells to self-destruct, raltitrexed limits its work to halting the growth and division of cells. Although the death of cells is the desired outcome in the cancer tumor, patients continue to suffer a loss of quality of life as their healthy body tissue endures the same attack as the cancer. Raltitrexed’s limit to growth and division is a welcome one for mesothelioma patients.
Clinical studies have shown a 23.6% response rate in patients being treated with both cisplatin and raltitrexed, compared to a 13.6% response rate in those only on cisplatin. In addition, the extended life times have increased in patients using both drugs to 11.4 months verses 8.8 months in patients on cisplatin alone. The length of time without cancerous progression has also grown from 4 months to 5.3 months with use of both drugs.
These improvements are a direct defense against the failing quality of life in mesothelioma patients. Not only is the patient’s body fighting the chemotherapy administered against the cancer, but also many other negative side effects characterized by a cancer patient’s illness. Neotropenia and anemia are just two of the harsh effects of chemotherapy widely experienced in those undergoing treatment. Both effect the blood cell count causing susceptibility to infections, fatigue and general weakness.
Raltitrexed has been licensed for use in the Czech Republic, Hungary, and Portugal. With many benefits proven in clinical tests, raltitrexed could make a significant difference in the quality of life for patients in the US and abroad.
Gene therapy research proves promising
Researchers in Baltimore have made a significant discovery concerning the behavior of mesothelioma in varying patients. Their findings may help them to predict patient responses to the disease, and possibly even control those responses in order to improve survival in those with malignant peritoneal mesothelioma.
Peritoneal mesothelioma refers to the formation of cancerous tumors in the mesothelial tissues of the abdominal cavity. Like other forms of mesothelioma, the disease is caused almost exclusively by asbestos fibers and is terminal in the overwhelming majority of cases. Unlike better known forms of the disease such as pleural mesothelioma, or mesothelioma of the lung lining, the mechanism which introduces the asbestos fibers to the area of the tumor is unknown. Some evidence suggests that peritoneal mesothelioma may result from the accidental ingestion of asbestos fibers, whereas pleural mesothelioma results from inhalation of the dangerous materials.
Patients suffering from peritoneal mesothelioma react to the disease in very different ways, a fact which lead researchers to further investigation. According to the Maryland researchers, “There is marked variability in its clinical behavior. Some patients die rapidly, and others survive for many years.”
The researchers believe that the differences in individual responses to the disease may lie in the expression of certain genes which affect the chemical “signals” transmitted to cells. In some patients, these signaling pathways cause cancerous tumors to grow and spread more rapidly, while in other patients the tumors appear to grow far slower. The researchers analyzed forty-one tissue samples from mesothelioma patients, and found that the “signaling chemicals” responsible for RNA production and protein synthesis differed between samples.
In one group the over-expression of certain pathways known as PI3K and the mammalian target of mTOR caused the presence of specific genes associated with a peritoneal mesothelioma survival of around 24 months. In patients where the same pathways and the genes which they are linked to were not present, survival rates were more than twice that time at some 69.5 months. When synthetic means were introduced to inhibit the expression of the PI3K and mTOR pathways, they found that the division and growth of cancerous cells was significantly impeded.
The scientists believed that further research into the significance of specific gene expression in peritoneal malignant mesothelioma patients was warranted. They asserted that the experiments already conducted highlight the importance of analyzing gene expression and further understanding the mechanisms that link these expressions with differing survival rates.
The study concluded: “Targeting the PI3K and mTOR signaling pathways may have significant therapeutic value in patients with MPM.”
Southwest Oncology Group testing new chemotherapy treatment
Southwest Oncology Group, one of the largest clinical trial cooperative groups in the United States, is conducting a new trial whose aim is to further understand a specific chemotherapy regimen used to fight malignant pleural mesothelioma.
Mesothelioma is a cancer of the mesothelium, a soft tissue found around the lungs, abdomen and heart which encases organ systems and promotes their smooth function. Pleural mesothelioma refers to the cancer when it attacks the lining of the lungs, or the pleural mesothelium.
Mesothelioma is a terminal disease, and is caused almost exclusively by exposure to asbestos fibers. When asbestos fibers are accidentally inhaled or ingested, they travel through the victim’s body until they become lodged in the mesothelial tissues. Asbestos fibers trapped in the mesothelium cause a scarring reaction which can spur the growth of malignant tumors.
Cancers in the body spread through cell division, and often require the development of new blood vessels to supply the malformed tumor tissues and continue growth. Chemotherapy aims to inhibit certain enzyme actions that are required for these cells to divide, thus slowing or stopping the growth of the tumor.
Mesothelioma is commonly treated with a specific chemotherapy treatment made up of both pemetrexed and cisplatin. While this treatment has demonstrated enough efficacy to become a commonly accepted mesothelioma treatment route, in many cases its effects are disappointing or even negligible. The Southwest Oncology Group is currently testing the effect of adding a third chemotherapy treatment to the regimen, cediranib maleate. The new treatment made up of all three chemotherapy drugs is being tested in patients who have not been treated previously for malignant mesothelioma with either surgery, chemotherapy, radiotherapy, hormonal therapy or any other form of treatment.
Cediranib maleate, which is also referred to as either AZD2171 or Recentin, is expected to stunt or stop the growth of new blood vessels which supply tumor growth with the nutrients necessary to grow and develop. This phase of the clinical trials, referred to as Phase I/II, is intended to study the side effects of the new treatment as well as discern the most effective dosage of the new additive.
Southwest Oncology Group is funded largely by the National Cancer Institute, and enrolls more than 6,000 cancer patients and healthy volunteers each year to study new drugs and treatment methods. Patients interested in participating in clinical trials of experimental drugs can contact the group for more details.
