Keytruda, Lung Cancer, and Mesothelioma

Keytruda - Clinical Trials

Keytruda (also known as pembrolizumab) is a new cancer-fighting drug that is making a big splash. Introduced by the pharmaceutical company Merck, Keytruda belongs to a class of drugs known as monoclonal antibodies. Unlike traditional chemotherapy drugs Monoclonal antibodies are specialized proteins that are part of the body’s own immune system.

So how does it work? Researchers have known for awhile that some cancers contain a specific protein called PD-L1 that helps to protect them from attack. Keytruda blocks this protein, allowing the immune system to attack and destroy the cancer cells.

Keytruda Shows Promise in Clinical Studies

In the summer of 2014, Merck launched a new study called KEYNOTE-024 whose goal was to see if Keytruda could do a better job of fighting cancer cells than some of the more traditional medications that are currently used. The study followed 305 patients with metastatic non-small cell lung cancer (NSCLC) who were previously untreated and whose tumors expressed high levels of the PD-L1 protein. Some of the patients received the standard chemotherapy treatment, which was usually a combination of carboplatin, cisplatin, pacilatexel and pemetrexed, while the rest were given Keytruda.

About 11 months later, researchers followed up with all the patients and discovered the following results:

  • Keytruda reduced the risk of cancer progression or death by 50% compared to the standard chemotherapy treatment.
  • The median (progression-free) survival for Keytruda was 10.3 months compared to 6 months with standard chemotherapy.
  • Even at six months into the trial, 62.1% of patients treated with Keytruda were alive and had no disease progression compared to 50.3% of those receiving standard chemotherapy.

By all measures, the results of this study were extremely impressive. Stefan Zimmermann of Lausanne’s University Hospital told reporters at a conference where the results were presented, “Remember this day. It’s a new day for lung cancer treatment.”

What Keytruda Means for Mesothelioma Research

Lung cancer is the biggest cause of cancer deaths globally, so it’s a logical starting point for many researchers to begin with when trying new drugs for cancer treatment. But the work doesn’t stop there. With the success of Keytruda in this trial, it is expected that research will expand to include its use in other types of cancer like mesothelioma.

In fact, clinical trials involving the use of Keytruda in patients with Mesothelioma are already underway. One trial in particular, called KEYNOTE-028, is looking at patients with malignant pleural mesothelioma – a cancer of the lining of the lungs that is caused by exposure to asbestos – to see if these patients have better outcomes with Keytruda than with standard treatments alone.

Keytruda is especially important because it is a drug that mesothelioma patients who have exhausted all other treatment could potentially turn to as a last resort. Although the trial is still in its beginning phase, early results are promising.

Dr. Roger M. Perlmutter, the president of Merck Research Laboratories said of the initial Keytruda trial, “These studies may represent a turning point in worldwide efforts to control lung cancer.” Only time will tell if these words prove to be prophetic, and it is hoped that with the Food and Drug Administration’s recent approval of Keytruda for the treatment of metastatic NSCLC that the same may soon happen for mesothelioma.

Mesothelioma Growth Slowed by Breast Cancer Drug

A drug most often associated with the treatment and prevention of breast cancer may offer a new way to treat pleural mesothelioma, too.

A new study conducted by Ireland’s Royal College of Surgeons and published in the medical journal Anticancer Research focuses on tamoxifen as a novel mesothelioma therapy.

How Tamoxifen Works

Tamoxifen helps fight breast cancer and protect high-risk women from getting it by blocking cancer cells from using the estrogen they need to grow.

Given that some types of mesothelioma tumors also appear to rely on estrogen to fuel their growth, the Irish scientists theorized that a drug like tamoxifen, which modulates estrogen receptors, could be used to enhance mesothelioma therapy.

Testing Tamoxifen on Mesothelioma Cells

The researchers tested tamoxifen in four different mesothelioma cells lines in the laboratory. Their goal was twofold – to determine whether tamoxifen could slow the growth of pleural mesothelioma and to see if it could improve the action of mesothelioma chemotherapy.

The four cell lines were treated with a combination of tamoxifen and the platinum-based drug cisplatin, one of the primary components of chemotherapy for mesothelioma patients. The news was encouraging for mesothelioma patients.

“Tamoxifen inhibited the growth of malignant pleural mesothelioma cells and also modulated their sensitivity to cisplatin,” writes study author Cormac Jennings, PhD, a molecular medicine specialist with Beaumont Hospital in Dublin.

A Surprise for Mesothelioma Researchers

Although the news was good, the study also produced some surprises. Even though tamoxifen appeared to work against pleural mesothelioma, it was not in the way the researchers had expected.

Instead of acting on the estrogen receptors in these ER-positive mesothelioma cell lines, tamoxifen repressed the expression of cyclins, proteins associated with cell division. The result was an interruption of the normal cell cycle for these mesothelioma cells and an increase in apoptosis, the natural process of programmed cell death.

“The ER-independent actions of tamoxifen on malignant pleural mesothelioma cell proliferation and cell cycle progression may have clinical benefits for a subset of patients with MPM,” concludes Dr. Jennings.

Tamoxifen has been used to treat breast cancer for more than 40 years. It is available in a generic form and is relatively inexpensive. It has not yet been studied in the treatment of mesothelioma patients.

Focus on Mesothelioma Education During Lung Cancer Awareness Month

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In the U.S., November is best known for the start of the holiday season with Thanksgiving on Nov. 24. However, families who have a loved one battling mesothelioma or lung cancer will not be celebrating – they will be focusing their efforts on understanding and fighting the cancers. This year, help them out by making November a month to educate others about mesothelioma and lung cancer by taking part in Lung Cancer Awareness Month.

The month, which emphasizes education and awareness of all things about lung cancer and other cancers affecting the respiratory system, such as mesothelioma, is getting a boost in visibility this year with participation by the International Association for the Study of Lung Cancer (IASLC). The IASLC is “leading a joint effort among a consortium of non-profit lung cancer patient advocacy organizations and individuals, to produce a coordinated, harmonized public awareness campaign for Lung Cancer Awareness Month (LCAM),” according to its website.

The consortium launched a new website, http://lcam.org/, and wants to fill it with stories and pictures from survivors and families affected by lung cancers. The group’s tagline, “Hope Lives – More Research. More Survivors.”, highlights the group’s dedication to improving survival for those affected by cancers of the lung.

Pleural mesothelioma is caused by inhalation or ingestion of airborne asbestos fibers. The fibers then become lodged in the lining of the chest, where, over the years, they begin to irritate the tissue leading to cancer. The disease has a very long latency period and is often not discovered until decades after exposure. The treatment protocol for mesothelioma is similar to that of lung cancer.

Lung Cancer and Mesothelioma Facts

  • Lung cancer accounts for about 27 percent of all cancer deaths, and is the leading cause of cancer death among both men and women.
  • 158,080 Americans are expected to die from the disease in 2016.
  • Each year, more people die of lung cancer than of colon, breast, and prostate cancers combined.
  • One in 15 Americans will be diagnosed with lung cancer in their lifetimes.
  • Mesothelioma is a terminal, asbestos-related cancer that affects the linings of the lungs, abdomen, heart, or testicles.
  • Many of the firefighters, police officers, and rescue workers from Ground Zero on September 11, 2001, may be at increased risk of contracting mesothelioma in the future.
  • Mesothelioma is diagnosed in close to 3,000 Americans each year, and approximately one-third of those diagnosed are military veterans.
  • There is no cure for mesothelioma.

“It is important that IASLC members help communicate the vast threat lung cancer poses around the world,” according to the IASLC. But, it is also important for the public to realize there is hope.

“We need the public and the media to understand that new research, diagnosis and treatment breakthroughs in the last 10 years have brought new hope to patients and their families.”

The Lung Cancer Alliance, with a mission of saving lives and advancing research by empowering those living with and at risk for lung cancer, says “Make the most noise ever for Lung Cancer Awareness Month” by adding your voice to the national movement. The Alliance is focusing its efforts on its campaign “Shine a Light on Lung Cancer” and encourages the public to do the same.

DOD Continues to Allocate Millions to Mesothelioma Research

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The U.S. House of Representatives recently passed the fiscal year 2017 Defense Appropriations bill and kept mesothelioma-eligible funding for 2017. Mesothelioma was first funded through the bill in 2011 and has been on the list every year since then.

The funding is available as part of the DOD’s Peer Reviewed Cancer Research Program (PRCRP). The DOD Appropriations Bill, 2017, which was submitted on May 19, allocates $30 million for distribution among eligible cancers through the PRCRP. In addition to mesothelioma, other cancers sharing in these research funds include: bladder cancer, brain cancer, colorectal cancer, listeria vaccine for cancer, liver cancer, lymphoma, melanoma and other skin cancers, pancreatic cancer, stomach cancer, and cancer in children, adolescents, and young adults.

An additional $12 million is set aside specifically for the lung cancer research program. The bill provides a total of $282 million for cancer research.

The Defense Appropriations bill funds critical national security needs, including military operations and readiness programs, as well as health and quality-of-life programs for U.S. troops and their military families. The PRCRP grants are offered with a goal to improve quality of life by decreasing the impact of cancer on service members, their families, and the American public. The entire bill provides $517.1 billion in funding.

“This bill fulfills the Congress’s most important responsibility – providing for the common defense. And it does so responsibly – funding those military needs that must be addressed now, planning and preparing for the future, and respecting the taxpayer by making commonsense budgeting decisions,” Chairman Hal Rogers said in the June 16th press release announcing the House’s passage of the bill.

The DOD is responsible for funding and promoting research on diseases related to military service. Veterans account for nearly 30 percent of all cases of mesothelioma, a cancer of the lining of the lung or abdomen, caused by exposure to asbestos. Former military troops have a higher risk of contracting asbestos-related diseases because of the wide use of asbestos in thousands of buildings and Navy ships from World War II until the 1970s.

“The Committee commends the Department of Defense for ensuring that projects funded through the various peer-reviewed cancer research programs maintain a focus on issues of significance to military populations and the warfighter,” noted the Committee members in the bill report. “This includes promoting collaborative research proposals between Department of Defense researchers and non-military research institutions. These collaborations leverage the knowledge, infrastructure, and access to clinical populations that the partners bring to the research effort.”

Close to 3,000 Americans are diagnosed with mesothelioma each year. There is no cure for the cancer.

Mesothelioma, Asbestos Lung Cancer, Asbestosis And Other Asbestos Disease

There are five main asbestos diseases including asbestos cancer quit blogging. Develop following exposure to asbestos material. These are malignant asbestos mesothelioma cancer, asbestos lung cancer, asbestosis, asbestos pleural thickening and asbestos pleural plaques, however, doctors that not regularly diagnose asbestos disease can misdiagnose (or be slow to give a diagnosis) what the condition is. This can lead to sufferers of asbestos disease wrongly concluding they do not have a right to make an asbestos compensation claim. It is therefore necessary for ladies with lung disease who are exposed to asbestos fibers to immediately contact a guru asbestos lawyer or asbestos attorney for advice and assistance in obtaining the best diagnosis if you find any uncertainty.

There are five main asbestos diseases including asbestos cancers that can develop following exposure to asbestos fibers These are malignant asbestos mesothelioma cancer, asbestos lung cancer, asbestosis, asbestos pleural thickening and asbestos pleural plaques, however,

Doctors that do not regularly diagnose asbestos disease can misdiagnose (or be slow to give a diagnosis). Exactly what the condition is because:

A history of asbestos exposure may not be volunteered to the doctor with an early stage as it might have occurred 30, 40, 50 or more years prior to seeing a doctor and may have been overlooked. A striking feature of asbestos disease is the long latency period between exposure and onset of symptoms, the fibers lying dormant for many people years before causing asbestos disease or symptoms in which medical advice is sought for.

Some asbestos diseases require exposure to only very few asbestos fibers to cause illness, especially mesothelioma end up being be do in order to just one fiber being inhaled into the lungs! This adds for the above mentioned difficulty of no, or only poor, recollection of exposure to asbestos fibers and accurate diagnosis.

As chest physicians become more aware of asbestos disease, due to its increasing incidence, and the need to ask patients at an early stage if they’ve ever been around asbestos fibers, these difficulties become much less of an issue, however, in accessory for early history taking these further difficulties regularly arise.

The radiological evidence (shown on x-ray films) can often misunderstood. Signify often final result an incorrect diagnosis being made in asbestos disease cases of pleural plaques and pleural thickening. Is definitely usually as a result of inexperience and also the fact that radiological evidence asbestos pleural plaque is similar, to the inexperienced eye, to asbestos pleural thickening and the other way around.

This extremely important in the context of asbestos UK disease litigation as asbestos pleural plaques is currently not thought to be a +injury+ from the UK courts for which compensation could be awarded! System in spite of most of the that pleural plaques sufferers were routinely awarded compensation for 2 decades prior in order to some Court of Appeal ruling in 06.

Accurate diagnosis in cases of asbestos pleural thickening can be a challenge due on the fact that apart with the potential for it to be radiologically confused with pleural plaques, it furthermore be mistaken for other non-asbestos related injuries or illnesses. For example, during the careful history taking in cases of suspected pleural thickening, it’s very important to ask the patient if offer ever the fractured rib or ribs. The healing process in the place of fractured rib can avoid radiological evidence that occurs on x-rays as pleural thickening. Other prior lung complications and scenarios can also leave behind such explanation.

Difficulties also arise attempting to attain an accurate diagnosis in the event of asbestosis. Asbestosis could be the scarring of lung tissue caused by asbestos fibers in the lungs. The particular issue here generally that scarring of lung tissue can be caused by other factors or foreign bodies entering the lungs and not only asbestos materials. Lung scarring or fibrosis appears identical shoes you wear on x-ray films involving what has caused it. Salvaging therefore crucial, perhaps more so than with any other asbestos disease, to ensure an early and very detailed status for significant exposure to asbestos fibers is taken and recorded as lung fibrosis can easily be diagnosed as asbestosis if the has suffered significant and high exposure to asbestos fibers in you will discover.

10 Options for the treatment of mesothelioma

                                               Photo Credit mesothelioma
As with any cancer, treatment for mesothelioma, it depends on the location of cancer, the progression of the disease, age and health status of the patient.
It is specialized in the disease, which will decide on the treatment line oncologist. The disease is difficult to treat and in most cases the prognosis is poor. Treatment options include:
1. If the diagnosis is made in the early stages, surgery may be recommended to remove all cancerous tissues. This means thoracoscopy, vats or video-assisted thoracic surgery, mediastinoscopy (used for staging), or laparoscopy. Often, doctors will advise palliative procedures like chest tube and pleurodesis, thoracoscopy and pleurodesis, pleurectomy pleuroperitoneal derivation or that treat the symptoms of mesothelioma rather than the disease.
2. Radiation is prescribed aggressively for mesothelioma patients and is often given in combination with surgery or to control symptoms, palliative. Research on using radiation therapy using implants or UV light therapy is in progress as traditional radiation therapy damages surrounding healthy tissue.
3. Chemotherapy is an option and around 12-20% of patients respond to drugs. Cancer drugs destroy cancer cells and prevent their spread. In mesothelioma, chemotherapy is not considered curative. The aim is to prevent the spread of the disease; reduce the tumor size before surgery, known as neoadjuvant therapy; destroy the tumor remains in the body after surgery; and to relieve pain and other discomforts, palliative chemotherapy. Experts recommend prescribing Alimta with cisplatin. These drugs have shown positive results, and it is now standard care for Mesothelioma not treatable with surgery.
4. Biological therapy using interleukin-2.
5. Immunotherapy where the body’s immune system is stimulated to fight the disease. Biological response modifiers, BRM, are used in treatment. These functions improve the immune system; regulate metabolic reactions promoting the growth of cancers; disrupting cell division of cancer; block or reverse processes that lead to the formation of cancers; and prevent the spread of cancer.
6. Gene therapy, where attempts are made to correct the gene sequence that causes cancer. It is of two kinds, replacement gene therapy and knockout gene therapy.
7. Administration of lovastatin a cholesterol-lowering drug.
8. photodynamic treatment where a photosensitive drug is activated using a laser. The process is done during the surgical removal of the cancerous tissues.
9. Draining of fluid in the chest or abdominal cavity followed by the introduction of drugs into the cavity to prevent fluid accumulation is performed for patients with uncontrolled accumulation of intense discomfort liquid derived from it.
10. The combination therapy or trimodal therapy meaning surgery accompanied by radiation and chemotherapy.
Often, complementary medicines are also used. Called to be holistic this kind of treatment focuses on the physical, mental, emotional and spiritual well-being of the patient.
In the case of mesothelioma, one can choose intractable new treatments clinical trials are underway in several laboratories and research centers. The best advice in the line of treatment would be recommended by the oncologist or physician.

New Lung Cancer Study May Improve Mesothelioma Therapy

Female researcher in a lab

New insight into the gene responsible for the most aggressive subtype of non-small cell lung cancer (NSCLC) could bring hope for mesotheliomapatients.

Researchers from UT Southwestern Medical Center identified a new way to target lung cancerthrough the Kirsten rat sarcoma viral oncogene homolog, also known as the KRAS gene.

Tumors that carry a mutation in this gene account for about 30 percent of lung cancer cases, which are usually aggressive with a poor prognosis.

Prior to the study, scientists had difficulty targeting the gene.

The KRAS gene produces proteins called K-Ras, which influence cell division. Mutations in K-Ras can result in normal cells dividing uncontrollably and turning cancerous.

This is an example of an epidermal growth factor receptor (EGFR).

EGFR is involved with the pathogenesis of malignant pleural mesothelioma (MPM), the most common form of mesothelioma.

While the study focused on lung cancer, new breakthroughs targeting mutated genes and cancer cells are beneficial to future treatments of mesothelioma, which is equally as aggressive as NSCLC.

Significance of Mutation Analysis in Mesothelioma Treatments

Asbestos exposure activates EGFR; however, because it is produced by a variety of cancers, it cannot be used to diagnose mesothelioma.

Advances with anti-EGFR drugs and targeted treatments can be significant in future treatments of pleural mesothelioma patients. Molecular profiling is essential for some pleural mesothelioma patients who may respond to anti-EGFR therapies.

The British Journal of Cancer in 2013 published a study that investigated the presence and frequency of EGFR gene mutations in pleural mesothelioma patients.

Researchers found EGFR downstream pathways are not rare in malignant pleural mesothelioma patients, and although none found in the study “seemed to be prognostically significant, they may support a more specific selection of patients for future trials.”

Findings Show Fatty Acids Play Key Role in Lung Cancer

UT Southwestern researchers determined enzymatic activity from the Fatty-Acid-Coenzyme A Ligase Long-Chain 3, or ACSL3 gene, is essential for the mutated KRAS genes to survive. Suppressing the ACSL3 gene causes these lung cancer cells to die.

Dr. Mahesh S. Padanad, first author and part of the UT Southwestern team, wrote in the study that “there is an urgent need for discovery of additional targets that inhibit lipid metabolism in cancer cells that could lead to targeted therapies: the discovery of the importance of ACSL3 in lung cancer meets this unmet need.”

To understand the biological significance of ACSL3 in lung cancer, researchers studied several complementary approaches, including cell lines, mice and human patient tumor samples.

Scientific journal Cell Reports published the study in August. The American Cancer Society Research Scholar grant, Cancer Prevention and Research Institute of Texas (CPRIT), UT Southwestern Friends of the Comprehensive Cancer Center and other research grants supported the study.

Clinical Trial Shows Success in KRAS Treatment

A recent collaboration at 67 medical centers and clinics in 12 countries reported some success in treatment of KRAS-mutant cancers using a compound of standard chemotherapy agent Docetaxel in combination with Selumetinib.

“A combination of chemotherapy and Selumetinib is significantly better than chemotherapy alone for this group of patients – better in terms of tumor response to therapy and in terms of survival times prior to advance of the disease,” Dr. Pasi A. Janne, a practicing oncologist and researcher at the Lowe Center for Thoracic Oncology, told Asebstos.com. “It suggests that for the first time we may have an effective treatment for KRAS-mutant lung cancer, which is the largest single subtype of the disease.”

The clinical trial found Selumetinib, manufactured by AstraZeneca, plus docetaxel has promising effectiveness but with a “higher number of adverse events than with docetaxel alone.”

Researchers said the findings warrant further clinical investigation.