Source: Yahoo News

Researchers from the MD Anderson Cancer Center at the University of Texas at Houston recently announced the results of study they conducted that showed that damage to particular cells that line the mouth is often indicative of damage to similar cells in the lungs and is potentially predictive of the development of tobacco-induced lung cancer, as well as other forms of cancer that tobacco is involved in. The research team enrolled 125 long-time smokers in their study and they looked at two genes that have previously been implicated in the development of cancer: p16 and FHIT. Long before any cancer actually develops, the genes that cause its later emergence have already sustained significant damage to their proper function, so the development of tests that can investigate and diagnose present gene damage are potentially very helpful in monitoring overall health and determining the likelihood of cancer development in at-risk populations.

In the present study, the research team investigated the status of p16 and FHIT in both the mouth and lungs of their sample population. They found that p16 was shut down in the lungs of 23 percent of the sample and in the mouth in 19 percent. FHIT was shut down in the lungs in 17 percent of the sample and in the mouth in 15 percent. Overall, the researchers found that in 95 percent of people whose genes were affected, the genes were affected in both the mouth and the lungs.

These are important findings because the researchers hope these results will lead to the development of easier screening tests, such as a simple mouth swab, for lung cancer and other cancers, such as mesothelioma. The development of more effective screening tests could save many lives, as most cases of lung cancer or pleural mesothelioma are only diagnosed when the diseases are in their later stages and are more difficult to treat effectively.

Labels: LungCancer, mesothelioma

Pemetrexed Plus Cisplatin Neoadjuvant Therapy Followed By Surgery and Radiation in Mesothelioma

Phase II trial of Neoadjuvant Chemotherapy with Pemetrexed plus Cisplatin followed by Surgery and Radiotherapy in patients with Malignant Pleural Mesothelioma stage I-III. The event-free survival is the primary endpoint for this study. This is a multicenter study and 53 Patients will be enrolled by June 2008...

Date First Received: September 12, 2005

Last Updated: February 11, 2008

Verified by: Eli Lilly and Company, February 2008

Clinical Trial Phase: Phase 2 | Start Date: June 2005

Overall Status: Recruiting

Estimated Enrollment: 53

Brief Summary

Official Title: “Phase II Trial of Neoadjuvant ALIMTA Plus Cisplatin Followed by Surgery and Radiation in the Treatment of Pleural Mesothelioma”

Condition Keyword(s):

• Mesothelioma

Intervention(s):

• Drug: pemetrexed
• Drug: cisplatin

Phase II trial of Neoadjuvant Chemotherapy with Pemetrexed plus Cisplatin followed by Surgery and Radiotherapy in patients with Malignant Pleural Mesothelioma stage I-III.

The event-free survival is the primary endpoint for this study. This is a multicenter study and 53 Patients will be enrolled by June 2008.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Outcome Measures for this Clinical Trial

Primary:

• Event-free survival baseline to objective progression, start of new therapy or death from any cause

Secondary:

• 1- and 2- year disease free survival baseline to post surgery
• To determine complete pathological response rate surgical complete response post chemotherapy, surgery and radiation
• Pharmacology toxicity every cycle
• Time to objective tumor response baseline to response of tumor
• Time to progressive disease baseline to measured progressive disease
• Overall survival baseline to date of death from any cause

Criteria for Participation in this Clinical Trial

Inclusion Criteria

• Histological proven diagnosis of stages I to III mesothelioma of the pleura.
• Adequate organ function including the following: adequate bone marrow reserve, hepatic, renal, pulmonary and cardiac functions.
• No prior systemic chemotherapy
• No previous surgical resection of mesothelioma, with the exception of previous chemical pleurodesis.
• No previous radiation therapy.

Exclusion Criteria

• Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
• Serious concomitant systemic disorders
• Second active primary malignancy
• Inability to interrupt aspirin or other nonsteroidal anti-inflammatory agents for a 5-day period
• Inability or unwillingness to take folic acid, vitamin B12 supplementation, or dexamethasone

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Eli Lilly and Company

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Mestre/Venezia 30170 Italy

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Milano 20141 Italy

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Padova 35100 Italy

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Rome 00128 Italy

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Napoli 80131 Italy

Overall Clinical Trial Officials and Contacts

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Study Chair Eli Lilly and Company

Overall Contact: They may be multiple sites in this clinical trial 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559

Additional Information

Information obtained from ClinicalTrials.gov on April 15, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00192010

Study ID Number: 8848

ClinicalTrials.gov Identifier: NCT00192010

Health Authority: Italy: Ministry of Health

Lilly Clinical Trial Registry

Clinical Trials Authorship and Review

Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: asbestos, cancer, ClinicalTrial, LungCancer, mesothelioma

Source: The Oncologist

Advances in imaging technologies have had a lasting impact on medical science. Better imaging techniques let doctors diagnose disease in a much more efficient manner and higher resolution scans can often be the difference between life and death. These advances are important to cancer research, especially to research in lung cancer and mesothelioma, as the ability to accurately diagnose these cancers at an early stage can dramatically improve a patient’s prognosis. An active area of research involving these two cancers involves the study of the diagnostic value of the various computed tomography (CT) modalities. Researchers from Italy have recently released the results of a study they conducted that looked at the efficacy of low-dose computed tomography (LDCT) scans for the diagnosis of lung cancer and pleural mesothelioma. The following is a summary of their findings.

Introduction to the Study

The researchers enrolled 1045 patients with a history of asbestos exposure into their study. Their aim was to evaluate the use of low-dose computed tomography (LDCT) scans for the early diagnosis of lung cancer and pleural mesothelioma. Because the link between asbestos exposure and these malignancies is well established, they expected to find a certain subset of related illnesses in some of these patients. The patients enrolled had to meet the following criteria: 40-70 years of age, no prior cancers or other severe conditions, no initial suspicion of lung cancer and no other CT scans during the previous two years.

All of the patients underwent both LDCT and chest x-ray (CXR) and the major analysis the researchers undertook was to look at how LDCT compared to CXR for the diagnosis of a thoracic malignancy.

Their results were revealing.

In nearly every way it could be, LDCT was more effective at diagnosis of lung cancer than CXR was. The researchers report detecting noncalcified nodules (early phases of lung cancer) with LDCT 19 times more frequently than with CXR. LDCT also identified 10 more full-on malignant events than CXR did.

As regards pleural mesothelioma, none of the study population at the time had developed mesothelioma, but because of its extreme latency period, this does not necessarily discount its use for the diagnosis of mesothelioma. LDCT did, however, detect a much higher percentage of pleural abnormalities than did CXR.

Conclusion

The results of this study certainly point to LDCT’s greater diagnostic efficacy for the various forms of lung cancer. The jury is still out, however, on the use of this imaging modality for the diagnosis of pleural mesothelioma, but its greater accuracy in diagnosing other pleural abnormalities is certainly a positive sign.

Labels: LungCancer, mesothelioma

Source: Utility of WT-1, p63, MOC31, Mesothelin, and Cytokeratin (K903 and CK5/6) Immunostains in Differentiating Adenocarcinoma, Squamous Cell Carcinoma, and
(Diagn Cytopathol. 2008 Jan;36(1):20-5)

The first step in a diagnosis of cancer is the definitive conclusion of the presence of malignant tissue. However, this tissue may not identify the particular form of cancer at work, so further analysis is often necessary. One of the techniques used for this latter diagnosis is immunostaining, where a tissue sample is treated with a reactive dye that becomes activated when it binds to a marker indicative of a certain form of cancer. The binding process then “stains” the tissue—providing a visual indication of the marker’s presence and, therefore, a determination of the type of cancer at hand.

One of the most difficult differentials to make is between malignant mesothelioma and poorly differentiated forms of adenocarcinoma of the lung and squamous cell carcinoma of the lung. Morphology analysis of the fluid from an effusion is not able to differentiate between these cancers, so scientists are searching for protein markers that can differentiate between them. Researchers from the University of Michigan School of Medicine have recently released a study that identifies possible markers.

Introduction to the Study

The search for biomarkers for mesothelioma and other cancers is an especially active form of research. The need for accurate differential diagnoses has driven researchers to experiment with a number of substances as possible markers, such as calretinin, CEA, BerEP4, CD15 and cytokeratins, but many of these do not have the high specificity required for such important decision-making. Some recent studies have recently identified a few more substances as possible makers—WE-1, p63, MOC31 and mesothelin—and it is these agents that the authors of the present study looked at. They also looked at the ability of cytokeratin staining to differentiate between the cancers.

The authors studied 43 samples of malignant effusions. 10 were adenocarcinoma (ADC), 15 were squamous cell carcinoma (SCC) and 18 were malignant mesothelioma, mainly pleural mesothelioma. Immunostaining for each of the four markers identified above (WE-1, p63, MOC31 and mesothelin) was performed on each sample.

WT-1

The authors found that WT-1 was perfect for determining a malignant mesothelioma diagnosis, as it stained in 100% of the mesothelioma cases and none of the ADC or SCC cases. Calretinin had previously been identified as the best positive marker for differentiating mesothelioma, but the authors recommended further study and greater use of WT-1 because of their excellent results.

P63

Antibody-staining against P63 showed significant staining for SCC, a lower threshold for ADC and none for mesothelioma. The authors support using a combination of P63-negative status and WT-1-positive status to differentiate mesothelioma from both SCC and ADC.

MOC31

The authors conclude that MOC31 wasn’t an effective marker by itself. It stained for ADC 100% of the time, 67% of the time for SCC and 35% for mesothelioma, so it could not differentiate between the malignancies enough on its own. However, when used in a panel with other antibody staining, the authors felt it could be used to differentiate between ADC/SCC and mesothelioma.

Mesothelin

Mesothelin is a marker that is under active investigation, but there are conflicting results returned from different studies regarding its efficacy. Some studies have come back with a 100% success rating for determining a mesothelioma diagnosis, but the authors of this study expressed disappointment at the results they obtained when staining for it. Their figures returned the following results: 100% ADC and 60% SCC, but only a figure of 47% for mesothelioma. The authors do not recommend mesothelin because of these results.

Cytokeratin Staining

The results for K903 and CK5/6 showed that ADC and SCC can be differentiated using cytokeratin staining, but it is only recommended if mesothelioma has been conclusively ruled out before the investigation.

Conclusion

The identification of new markers in cancer diagnosis is an important advancement on our knowledge. Early identification allows the patient to receive earlier treatment, which can be greatly beneficial. With a malignancy such as malignant mesothelioma, which has generally resisted long term treatment, early diagnosis is essential to maximizing patient response.

Labels: LungCancer, mesothelioma

Source: Australasian Radiology

One of the most difficult aspects of treating cancer is the distinct number of forms it can take. While most cancers follow particular biological patterns, the literature is full of examples that do not follow these general trends. For example, in patients who present with a number of different tumors, metastasis is most often suspected as it is very rare for a single person to have multiple primary tumors at one time. Another relative rarity is for one form of cancer to mimic an entirely different form. Imaging tests and morphology analysis can usually identify the type of cancer present in any one patient, but in some cases, these techniques may not return the proper diagnosis, so immunohistochemical (IHC) analysis may be necessary to properly identify the cancer at hand.

In a recent case study from Japan, doctors describe a man whose presentation violated both of the principles just described. The patient was diagnosed with pseudomesotheliomatous adenocarcinoma of the lung, which is a rare lung cancer that morphologically mimics pleural mesothelioma, as well as squamous cell carcinoma of the esophagus and adenocarcinoma of the stomach.

Case Study

The patient presented as a 78 year-old man with shortness of breath and right chest pain. He was a smoker without known asbestos exposure and while his previous medical history was generally insignificant, his presentation was quite remarkable. A CT scan revealed diffuse pleural thickening in the right thorax and PET showed significant pleural involvement. A biopsy of the pleural mass was performed by video-assisted thoracoscopic surgery (VATS). Pictures from VATS also showed pleural thickening with diffuse spread. All signs pointed to malignant mesothelioma. However, IHC analysis of the biopsy sample revealed adenocarcinoma of the lung, not mesothelioma. The final diagnosis given was pseudomesotheliomatous adenocarcinoma of the lung. This rare form of lung cancer has a similar growth pattern to diffuse malignant mesothelioma and typically shares its poor prognosis as well, with a median survival figure of eight months from diagnosis.

Along with the tests that revealed the pseudomesotheliomatous adenocarcinoma, the patient also underwent an upper gastrointestinal endoscopy, which is a procedure that allows a doctor to view and biopsy the interior lining of the esophagus, the stomach, and the duodenum (the first part of the small intestine). The procedure revealed tumors in the esophagus and the antrum, which is the cavity in the stomach where food collects prior to its passage into the small intestine. Biopsy of each tumor revealed they were separate, primary sites: the esophageal tumor was a squamous cell carcinoma, while the stomach tumor was an adenocarcinoma. Analysis of the stomach tumor and the pleural malignancy showed they, too, were separate primary sites, so metastasis was not involved in any manner with the patient’s presentation.

As there are no treatment guidelines for this combination of cancers, the doctors treated the man in a palliative manner. He died six months after diagnosis, due primarily to heavy tumor growth in the pleural areas.

Conclusion

This patient’s presentation was remarkable for having multiple primary cancers, as well as for one of them being pseudomesotheliomatous adenocarcinoma. When multiple tumors are present, metastasis is nearly always at work. The authors report on a previous study of 5456 autopsy cases that described 285 cases of double primary cancer (5.2%) and only 58 cases of triple primary cancer (1.1%). Immunohistochemical analysis clearly showed three primary cancers in this man, placing him within the 1.1% figure from the previous study. It should be no real surprise then that the authors also state this is the first case in the literature of pseudomesotheliomatous adenocarcinoma concurrent with esophageal cancer and stomach cancer. Pseudomesotheliomatous adenocarcinoma is itself a rare cancer. Morphologically it resembles pleural mesothelioma and its diffuse nature is unlike the majority of other forms of lung cancer, so it’s easy to mistake the one for the other. Immunohistochemical analysis is an effective means of differentiating the two cancers, as each presents with specific markers that IHC can identify. The authors recommend IHC in the diagnosis of any pleural malignancy because of its ability to accurately diagnose the particular cancer involved.

Labels: LungCancer, mesothelioma

Source: Occupational and Environmental Medicine

Asbestos exposure is a constant concern for workers in shipyards. There is evidence to suggest that these workers are much more likely to come down with an asbestos-related disease than other professions. A study looking at the health patterns of a group of 4702 workers of a Coast Guard shipyard was recently completed and the results did show a greater mortality figure that is most likely caused by asbestos. The study examined workers employed from January 1, 1950 through December 31, 1964 and followed them through December 31, 2001. The findings showed an excess mortality rate for a variety of causes, most notably respiratory cancers, lung cancer, mesothelioma and emphysema. While length of employment wasn’t a factor for most of the other problems, mesothelioma incidence showed a definite increase if the person had worked at the shipyard for longer than 10 years. The study concluded that the greater morality rate was most likely due to asbestos exposure.

Labels: asbestos, LungCancer, mesothelioma

Source: Eli Lilly

Eli Lilly has submitted an application with the European Medicines Agency (EMEA) for the approval of Alimta^®, in combination with cisplatin, as a first-line treatment for advanced non-small cell lung cancer (NSCLC). The EMEA has previously approved Alimta as a single agent, second-line therapy for advanced NSCLC.

The submission is based on the results of a recently-completed study that compared Alimta plus cisplatin to Gemzar^® plus cisplatin and showed that the Alimta treatment regimen had similar efficacy to the Gemzar-based one, but had a better toxicity profile and greater convenience for the patient.

Gemzar is a leading first-line treatment for NSCLC.

Aside from its previously-approved use for NSCLC, Alimta has also been approved, when used with cisplatin, for the treatment of malignant pleural mesothelioma.

Labels: LungCancer, mesothelioma

Source: Wall Street Journal

In a supplement published in the medical journal Chest, the American College of Chest Physicians offered the first comprehensive analysis on the use of alternative and complementary medicine in the treatment of lung cancer. The researchers examined over 100 published studies regarding alternative or complementary medicine in an attempt to quantify the benefits and to identify the problems regarding these modalities. Federal studies have shown that more than half of all Americans have used some type of alternative therapy in their lives and that number increases when cancer is involved. Historically, most doctors have not had the knowledge of these treatments to discuss them with their patients, so the publication of these guidelines represents a genuine advancement in the knowledge of cancer treatment.

The report showed that herbal supplements are, at best, generally not very effective and, at worst, possibly a real problem as some of them will interfere with chemotherapy, radiation or other standard cancer treatments. A notable exception to this warning is the use of vitamin B12 and folic-acid supplements for people being treated with the chemotherapy drug pemetrexed, which is marketed as Alimta^® and is the standard chemo drug for people with malignant mesothelioma. The report indicates that the published research on supplements isn't especially deep, so it does not say that all supplements should be stopped—it merely indicates that supplements need to be evaluated for potential side effects and interactions with other agents.

The report treats acupuncture and other "mind-body" modalities more favorably than supplements and recommends many of them for particular conditions. Acupuncture is recommended for pain relief and to control the nausea and vomiting that is associated with chemotherapy. However, patients who are prone to excessive bleeding should be cautious about the use of acupuncture and should only be treated by a professional with experience in treating cancer patients. Meditation is recommended to reduce stress, while yoga and other relaxation techniques may help improve sleep. Massage is recommended for general pain and anxiety, as is hypnosis, but like acupuncture, those with a tendency to bleed should avoid deep-tissue massage.

The publication of these new guidelines for alternative and complementary medicine is an important advancement in our knowledge of cancer treatment. It is hoped that patients will be well-served with this new knowledge.

Labels: cancer, LungCancer, mesothelioma

Source: World Health Organization

The World Health Organization is calling on governments to enact meaningful reform to workplace safety laws and to increase the measures used to protect workers from work-related injury or death. At least 200,000 people die every year from work-caused cancers and millions more are regularly exposed to carcinogenic agents that can dramatically shorten their life expectancy. Mesothelioma, lung cancer and leukemia are just three examples of work-related cancers that can be prevented with the passage and enforcement of meaningful reform.

Specific WHO recommendations include:

• Stop the use of asbestos;
• Introduce benzene-free organic solvents and technologies that convert the carcinogenic chromium into a non-carcinogenic form;
• Ban tobacco use at the workplace; and
• Provide protective clothes for people working in the sun.

The majority of workplace-related deaths currently occur in the developed world, but developing nations represent a new horizon of workplace health epidemics. The WHO's policy recommendations are made to governments in both the developed and the developing world in order to protect workers everywhere.

Labels: asbestos, LungCancer, mesothelioma

Source: News-Medical.Net

Researches from the Ireland Cancer Center have discovered a mutation in the epidermal growth factor protein (EGFR) that causes resistance in lung cancer cells to targeting agents, such as Tarceva, that attempt to halt the spread of cancer cells by disrupting the receptor responsible for tumor growth. Tarceva has been successfully deployed in clinical settings, with approximately 10 percent of patients achieving complete remission, but if the cancer returned, it was no longer successful in blocking tumor growth. The researchers discovered that a mutation altered the shape of the protein's drug-binding pocket so Tarceva no longer "fit" the pocket and, therefore, was not able to properly bind to the site to suppress tumor growth. The researches have developed compounds to avoid this resistance through an innovative use of different combinations of medicines. It is thought that the next generation of Tarceva-like drugs, some of which are already in development and starting clinical trials, will overcome these problems and prove even more effective for cancer treatment.

The research term, led by Balazs Halmos, MD, a lung cancer specialist and Assistant Professor of Medicine at Case Western Reserve University School of Medicine, received an award for its research at the recent American Association for Cancer Research meeting.

Labels: LungCancer

Source: Rosetta Genomics

The NYU Medical Center, one of the world's premier academic medical institutions, has partnered with Rosetta Genomics, a leader in the development of microRNA-based diagnostics and therapeutics, to jointly-develop early detection diagnostic tools for lung cancer and mesothelioma. Dr. Harvey Pass, Professor and Chief of the Division of Thoracic Surgery and Thoracic Oncology at NYU Medical Center, describes a test "... that will be able to detect cancer at an ealy stage using a simple blood draw...." The test will use a proprietary protocol developed by Rosetta Genomics to extract microRNAs, which are a recently-discovered form of RNAi that act as protein regulators and have shown promise as biomarkers for a variety of cancers.

Labels: LungCancer, mesothelioma

Source: Billings Gazette

Libby, Montana is the location of what the EPA calls "the worst case of community-wide exposure to a toxic substance in U.S. history." One of Libby's major revenue sources was its vermiculite mine, but in 1990 it was discovered that the mine was contaminated with asbestos and that this contamination had exposed thousands of people to the many dangers of asbestos exposure, such as lung cancer and mesothelioma. There have now been over 192 deaths and 345 other cases of people made ill because of exposure to the asbestos-contaminated mine.

The primary responsibility for care and screening for these victims has been The Center for Asbestos Related Disease, a 2003 spin-off from the hospital in Libby. While the Center's main goal has been the care and screening of more than 1500 patients, the Center is also dedicated to researching new treatments and diagnostic techniques. The Center works in conjunction with other organizations, such as the Mesothelioma Applied Research Foundation, on a variety of research projects. One of its current projects is studying the actual asbestos-subtype found in Libby, as it differs in significant ways from the most common form of asbestos, chrysotile. Unlike chrysotile, whose fibers are serpentine-shaped and flexible, the type of asbestos found in Libby has hard, needlike fibers.

In 2001 the federal Agency for Toxic Substances Disease Registry completed a study which found that fully 19 percent of the population in and around Libby had physical signs of health-related abnormalities consistent with asbestos exposure.

Labels: asbestos, LungCancer, mesothelioma

Source: ScrippsNews

The Utah Department of Health has concluded that people who lived within two miles of two old vermiculite plants with heavy asbestos contamination in Salt Lake City have a fifty percent greater chance of developing lung cancer than people who live in other parts of the state. While the data didn't conclusively establish a causative relationship between the asbestos contamination and the lung cancer incidents, the high correlation rate has prompted the state to become more concerned about the potential health risks posed by these old plants. Two years ago the state, along with federal agencies, spent more than $7 million in a Superfund cleanup of the two plants.

Utah's Department of Environmental Quality, in partnership with the EPA, is now launching a search for people who have worked at the plant or lived in the surrounding neighborhoods.

The vermiculite plants received their stock from Libby, Montana, whose vermiculite mining industry was destroyed when large-scale asbestos contamination was discovered in its vermiculite ore mine in 1990. There have been more than 200 asbestos-related casualties from the mine itself, and many others have been sickened by the asbestos exposure. The EPA declared Libby, Montana to be the "worst-case of community-wide exposure to a toxic substance in U.S. History."
(http://en.wikipedia.org/wiki/Libby,_Montana)

Labels: asbestos, LungCancer, mesothelioma