Compound that may halt mesothelioma
Asbestos in older homes is causing a new wave of lung disease among renovators. Credit: Thinkstock
Research into a treatment for asbestosis and mesothelioma is showing promising results, and has real potential to short-circuit the progression of the disease, says a Sydney microbiologist.
Associate Professor Tony George and his co-researchers have discovered a compound they hope will be developed into a puffer-administered medication to treat the growing number of Australians diagnosed with incurable asbestos-related lung disease.
The team has found that the compound stopped the development of mesothelioma tumours in 60-80 per cent of asbestos-exposed mice in 30-week laboratory trials.
In earlier experiments on human lung cell cultures it was effective in preventing a cascade of events typically triggered by the presence of asbestos fibres, such as a rise in harmful oxygen radical levels.
At a genetic level, the compound short-circuits the pathways to cell death
typically caused by asbestos fibres, says Dr George, of the ithree institute at the University of Technology, Sydney (UTS).
"We think the compound could be used through a puffer or a nebuliser, just like those used with asthma, where it could either prevent the fibres taking hold in people exposed to asbestos, or improve the condition for people suffering now," he says.
Mesothelioma is an aggressive, incurable cancer in the lung lining, caused by exposure to asbestos fibres. It can take 20 to 50 years after exposure to appear.
Asbestos fibres lodged in the lung can't be removed and typically cause inflammation of the pleural lung lining. Over time, tumours develop in the deeper mesothelioma layer.
After two years of cellular-level laboratory work, the team conducted trials with the compound on mice bred for susceptibility to mesothelioma.
The trials showed that the immune-suppression typical in asbestos exposure was overcome by the compound, allowing the body's defence system to start to act against the asbestos fibres.
The compound seemed also to have a preventive effect.
Dr George and his team have applied for a patent on the compound.
They are working with SPARK Sydney mentors with hopes that a pharmaceutical company will turn a product around in the next five years.
SPARK Sydney director Professor Michael Wallach says the program emulates a successful Stanford Medical School model and aims to get research benefits to patients more effectively.
"We selected Dr George's project because it satisfies an important, unmet need and we think in two years, with our support and mentoring, he should be able to get to a proof of concept that will be taken up by a pharmaceutical company."
Molecular biology research can take decades to move from discovery to cure.
However, mesothelioma patients don't have decades – most have only months, says Theodora Ahilas, who has become intricately familiar with the disease and its impacts after 24 years as an asbestos compensation lawyer.
"People who are diagnosed with these diseases need to have something that gives them hope. They need to know that there is some treatment which will give them a longer life expectancy and some quality of life."
The average lifespan after diagnosis is about nine months; even the most rigorous chemotherapy is able to extend average life expectancy by only three months. Dr George says there is potential for the new compound to complement chemotherapy.
Australia has the world's second highest rate of mesothelioma.
Safe Work Australia figures show about 700 people in Australia die from mesothelioma or asbestosis annually. Mesothelioma rates have climbed since the 1960s, initially from those exposed in mining and manufacturing. A new wave of mesothelioma cases is now becoming evident among home renovators, both men and women.
Ahilas says people may be exposed to asbestos in home renovations today and go on to develop mesothelioma in 30 years' time, making it critical that better treatments are developed.
"There's a difference between being diagnosed with a disease which robs you of your life in three to six months and a disease which gives you five to 10 years."
Explore further: Idiopathic pulmonary fibrosis cases linked with asbestos exposure
Stage 4 Cancer – MesotheliomaStage 4 is the final, most advanced stage of mesothelioma. Traditional surgery is usually not an option, and most treatments aim to ease symptoms and reduce pain.
- Overview
- Cancerous cells found throughout the body
- Aggressive tumor growth
- Advanced symptoms
- Treatment
- Chemotherapy slows tumor growth
- Radiation reduces tumors
- Removal of fluid buildup
- Pain medication and oxygen therapy
By stage 4 mesothelioma, the cancer has metastasized, or spread beyond the point of origin to other parts of the body. It is the most advanced stage and the most difficult to treat because the few traditional treatment options available cannot remove all the tumors.
Your outlook depends largely on the extent of tumor growth and how well you respond to treatments. At this end-stage cancer, many patients are too weak to withstand aggressive surgeries.
While stage 4 mesothelioma — commonly expressed with Roman numerals as stage IV — is considered terminal, continued advancements in palliative treatments can help you live longer and have a better quality of life. Some stage 4 patients continue to defy the odds, living years after their initial mesothelioma prognosis.
Fast Fact: The three systems commonly used to define stages of pleural mesothelioma (Bringham, TNM and Butchart) categorize stage 4 on similar characteristics and behaviors. Butchart and TNM note that the cancer has metastasized to distant organs, while Brigham designates that surgery is not a viable option.
Symptoms of Stage 4 Mesothelioma
Symptoms of stage 4 mesothelioma are quite severe
because tumors have spread beyond the lungs. Common symptoms of late-stage mesothelioma include:
- Fever
- Night sweats
- Chest pain
- Shortness of breath
- Tightness of chest
- Fluid buildup in chest or abdomen
- Abdominal pain
- Fatigue
- Weight loss
- Anorexia
- Malaise
Learn more about symptoms Stage 4 Mesothelioma Treatment Options
In most cases, stage 4 mesothelioma, also known as end-stage mesothelioma, cannot be successfully cured. Traditional surgery is typically not an option, but palliative treatments, such as chemotherapy and radiation therapy, slow tumor growth and reduce tumor size.
Surgery
While the spread of tumors is usually too vast at stage 4 for doctors to remove all growths, some patients can benefit from less extensive surgical procedures. Surgeons can attempt to remove as much tumor mass as possible. They can also target only problematic tumors so patients breathe more comfortably and experience less pain.
Less invasive procedures, such as a thoracentesis, paracentesis and pericardiocentesis remove fluid buildup near the main tumor, relieving pain and breathing difficulties.
Learn more about mesothelioma surgeries Chemotherapy
Chemotherapy is one of the most common treatment options for stage 4 mesothelioma. Chemotherapy drugs slow tumor growth and may shrink tumors in some cases, helping to alleviate symptoms and extend survival. Wayne State University researchers in 2016 found chemotherapy more than doubles life expectancy for malignant mesothelioma patients, including those in stage 4. Combining chemotherapy with surgery extended survival even longer.
The most commonly prescribed chemotherapy regimen for pleural mesothelioma is cisplatin or carboplatin combined with Alimta (pemetrexed).
Learn more about chemotherapy Radiation Therapy
Doctors don't always treat stage 4 mesothelioma with radiation therapy, but they may recommend the procedure depending on your tumor growth and overall health. Radiation therapy at this stage might be able to reduce the size of tumors, which can lessen chest pressure, decrease pain and improve breathing.
Learn more about radiation therapy Clinical Trials
Certain people in stage 4 may qualify for mesothelioma clinical trials. Some clinical trials investigate the value of various treatment combinations for late-stage mesothelioma.
A 2016 study published in The Annals of Thoracic Surgery showed a correlation between the use of light energy or photodynamic therapy and late-stage mesothelioma survival. A subset of patients with pleura mesothelioma achieved a median overall survival of 7.3 years compared to the usual one-year prognosis.
Learn more about clinical trials Supportive Care
Supportive care helps to relieve symptoms and improve quality of life. At stage 4, doctors may recommend pain medication, oxygen therapy and respiratory therapies to control pain and improve lung function.
Numerous long-term mesothelioma survivors have incorporated complementary and alternative medicine therapies into their treatment plan. Certain complementary therapies are known to improve survival, ease symptoms, reduce treatment side effects and enhance quality of life. These treatments include herbal medicine and holistic therapies, mind-body therapies (yoga, qigong and tai chi) and nutritional therapy.
Learn more about alternative therapies
You have to look way outside the box to find good information on alternative treatment. There’s not a lot of stuff out there in the mainstream medical community, and that’s discouraging. But when you learn about it, and how integrative medicine works, it will blow you away.”— Beth Mixon, diagnosed with peritoneal mesothelioma in 2000
Find a Top Mesothelioma Doctor
We can help you or a loved one connect with the nation's top mesothelioma doctors and treatment centers.
Late Stages by Mesothelioma Type
Stage 4 typically refers to pleural mesothelioma, the most common type of the asbestos-related cancer.
There is no official stage 4 for peritoneal mesothelioma, which accounts for roughly 20 percent of all cases.
However, it is generally accepted that peritoneal patients with extensive tumor spreading are classified as stage 4.
By this point, the cancerous tissue is more extensive and tumors have spread outside of the peritoneal lining — the protective lining of the abdomen where the cancer initially develops.
Like pleural mesothelioma, surgery is likely not an option at this phase. This includes heated intraperitoneal chemotherapy (HIPEC), a promising peritoneal treatment that combines surgery and heated chemotherapy.
“A stage 4 mesothelioma diagnosis doesn’t mean there is no hope or options. It’s important to connect with a medical oncologist that is experienced with mesothelioma to understand your treatment options. Remember, you are the decision maker. Your specialist is there to give you guidance. ” — Karen Selby, RN
Stage 4 Prognosis & Life Expectancy
At stage 4 the cancer is likely to continue to spread, which can lead to respiratory failure or heart failure if tumors spread to the heart.
The median survival rate for stage 4 mesothelioma is 12 months. A positive response to treatment can extend survival, and patients with good prognostic factors often live longer than average. Prognostic factors associated with better survival include having the epithelial cell type, being in good overall health, younger in age, female and having no signs of blood disorders.
Mesothelioma is considered a heterogeneous cancer, meaning no two cases are the same. For this reason, survival statistics cannot predict how long someone with mesothelioma will live. Some people have particularly slow-developing mesothelioma, and some respond surprisingly well to treatment.
What’s Next After a Stage 4 Mesothelioma Diagnosis?
Although stage 4 is the most advanced of the mesothelioma stages, some patients, especially those in good overall health, live far beyond their prognosis. Through a variety of treatments, groundbreaking clinical trials and healthy life choices, you can beat the odds and become a survivor. Consider the following:
- Get a second opinion from a mesothelioma specialist.
- Find financial assistance available to offset potential financial burden.
- Enroll in a clinical trial. Consult with your doctor to determine if you are eligible.
- Try alternative and complementary treatment options.
- Exercise and maintain a healthy diet to improve mood and quality of life.
- Join a support group to connect with others coping with mesothelioma.
- Make time for hobbies and activities that bring you joy.
- Read stories about other mesothelioma survivors.
A stage 4 mesothelioma diagnosis can be devastating, but it doesn’t mean it’s a death sentence. A positive outlook will do wonders when combined with a variety of treatments.
Additional Resources
Five Prime Announces Updated Data In Mesothelioma Patients From Ongoing Phase 1b Trial Of FP-1039 At ESMO 2017 Congress
Objective response rate of 48% and six-month disease control rate of 81% in patients at or below the maximum tolerated dose level; progression free survival of 7.4 months
Progression-free survival correlated positively with increasing expression levels of tumoral FGF2
SOUTH SAN FRANCISCO, Calif., Sept. 10, 2017 (GLOBE NEWSWIRE) -- Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing innovative immuno-oncology protein therapeutics, announced that updated data from the ongoing Phase 1b trial of FP-1039/GSK3052230 (hereafter FP-1039) in mesothelioma patients were reported today in an oral presentation at the European Society for Medical Oncology (ESMO) 2017 Congress in Madrid, Spain. The presentation titled "Multicenter, Nonrandomized, Open-Label Phase 1b Study of FP-1039/GSK3052230 with Chemotherapy: Results in Malignant Pleural Mesothelioma (MPM)" by Dr. Jose Trigo et al., is available at http://www.fiveprime.com/news-media/publications-presentations. "We are encouraged by the results of FP-1039 in the front-line treatment of malignant pleural mesothelioma, a rare aggressive cancer with a poor prognosis," said Helen Collins, M.D., Senior Vice President and Chief Medical Officer of Five Prime. "The majority of patients across all dose levels experienced tumor reduction. While this is single-arm data, we believe the findings compare favorably to historical data for chemotherapy alone. In addition to the safety and efficacy results, duration of progression-free survival correlated positively with increasing expression levels of tumoral FGF2." The mesothelioma arm of the open-label Phase 1b trial evaluated weekly infusions of FP-1039, an FGF ligand trap, in combination with first-line pemetrexed and cisplatin chemotherapy in patients with untreated, unresectable MPM. Following the dose escalation portion of the trial, 15 mg/kg weekly was identified as the maximum tolerated dose (MTD) for FP-1039 and established as the dose for expansion in patients with MPM. The primary study endpoints are safety and overall response rate (ORR), disease control rate (DCR) at 6 months, progression free survival (PFS) and exploratory translational objectives. The poster includes data from MPM patients who had received FP-1039 as of the March 17, 2017 cut-off