Source: The Journal of Thoracic and Cardiovascular Surgery

Extrapleural pneumonectomy (EPP) and pleurectomy/decortication (PD) are the two major surgical options for the treatment of pleural mesothelioma. An EPP is usually described as the complete resection of the pleura, the pericardium, the diaphragm and the entire lung on the affected side. With pleurectomy/decortication the lung is spared, but both the parietal and visceral pleurae are removed, as are the pericardium and the diaphragm if necessary. Both procedures are considered radical surgery, with EPP the more invasive of the two.

There is considerable controversy and debate in the mesothelioma community regarding which of the procedures is the most effective and what the conditions are that should govern the choice of the one over the other. Some previous studies have shown that patients who undergo PD are less likely to experience serious consequences and may have a longer post-surgery median survival, but the conclusions of these previous studies have often been questioned due to small sample size or an inability to directly compare the patient cohorts who completed the procedures.

In an attempt to settle this controversy, doctors from some of the country’s premier mesothelioma treatment centers have recently released the results of a study on the efficacy of EPP vs. PD in a large cohort of patients. The results of the individual treatments were analyzed on a number of different levels and the resulting analysis is the most complete yet offered about the relationship between EPP and PD and the conditions under which each procedure should be used.

Overview of the Study

The authors of the study undertook a retrospective analysis of 663 total patients who underwent an EPP (n=385) or a PD (n=278) between 1990 and 2006 at one of the following cancer centers: Memorial Sloan-Kettering Cancer Center, The National Cancer Institute or the Karmanos Cancer Institute. In looking at the historical records of these patients, their analysis compared not only the overall efficacy of the procedures themselves, but also the effect the various sub-groups had within the two major cohorts: histology, tumor staging, performance status, age, gender, etc., etc.

A number of important differences separate the present study from previous ones that also involved these procedures. In many of the prior studies, the surgical method was written-in to the study design itself and the actual procedure was only a part of the subsequent analysis. The procedures themselves were rarely compared directly and when they were other study factors would often limit the scope of the conclusions that could be drawn from the results. Another major difference between this study and previous ones was that the end points of earlier studies often looked only at time to progression, instead of overall survival, as the present study does. It is for these reasons, as well as others—such as the large sample size—that the authors describe this study as the largest, most comprehensive study yet completed on the use of extrapleural pneumonectomy versus pleurectomy/decortication.

As we said above, this study looked at 663 mesothelioma patients who underwent either EPP or PD during a sixteen-year period. Most patients were older males who presented with Stage II or Stage III disease characterized by the epitheloid histological subtype. However, there were important differences between the two groups. The patient cohort who underwent PD were on average older than the EPP group and more often presented with early stage disease, while the EPP group were more likely to receive some form of multimodal treatment and more often presented with epitheloid mesothelioma than did the PD group. The EPP group was also more likely to demonstrate more adverse post-surgical events than the PD was likely to.

When taken as an entire group, median survival was determined to be 14 months. However, this figure is truly an average and masks some very interesting findings. The over-all five year survival figure for the entire group was 12%. For patients who presented with Stage I disease, median survival rose dramatically to 38 months, while patients with stage II disease demonstrated a median survival of 19 months. Patients who were Stage III at time of presentation had a median survival of 11 months, while those with Stage IV disease averaged 7 months from diagnosis.

Other analyses that showed a significant impact on survivability were epithelial histological subtype, female gender and multi-modal therapy: all of which increased survival times.

A univariate analysis that compared PD to EPP showed that patients who underwent PD were associated with a significantly better median survival than did patients with EPP. However: this conclusion disappears when the analysis takes on a multi-variate methodology by considering the characteristics of the patient’s total presentation. When controlling for tumor stage, no significant differences were found between the PD group and the EPP group. The same is found when tumor stage is replaced by histology or gender. The differences that do exist between these cases are not significant enough to conclude that one procedure is somehow “better” or “more appropriate” than the other one is if presentation-specific elements are not accounted for. In fact, the authors specifically note the importance of taking the patient’s total presentation into account when deciding between the procedures.

In a discussion included at the end of article between the study’s lead author and peer reviewers of the study, Dr. Raja M. Flores, the lead author, and Dr. David Sugarbaker, Chief of the Division of Thoracic Surgery at Brigham and Women’s in Boston, discuss the importance of achieving macroscopic complete resection (MCR), i.e. removal of all visible tumor, to maximize the treatment’s efficacy. The choice of procedure will be made at the time of the thoracotomy, which is the procedure to open the chest cavity for surgery, and should be guided by the extent of tumor present. If the disease is caught in the early stages, P/D might suffice for MCR, but for advanced disease with significant spread and tumor bulk, an EPP is often the only procedure that could potentially achieve MCR, so that is the procedure that should be used.

Dr. Flores specifically states the two procedures are not interchangeable and they should not be seen that way.

Conclusion

The question of EPP vs. PD has long been a controversial debate among mesothelioma physicians. The authors of this study state that decisions on which procedure to use have more often been the result of surgeon bias rather than the application of sound science and one of their goals for the study was to help inform physicians on this question. In this, they have succeeded in providing valuable evidence regarding the efficacy and applicability of both extrapleural pneumonectomy and pleurectomy/decortication for the treatment of pleural mesothelioma. Neither procedure leads to statistically significant differences in overall survival, but each procedure is given a clear domain for use: PD for early stage disease and EPP for later stage disease or disease with a heavy tumor burden.

Even as they call for more studies comparing these two procedures, the authors have succeeded in making an important contribution to the controversy surrounding EPP vs. PD. However, neither procedure represents a truly curative approach to mesothelioma and the authors also call for more study and development of non-surgical treatments, as well as for more effective adjuvant therapy.

Labels: mesothelioma

Source: Cytopia Limited

Cytopia Limited, a privately-held biotechnology firm from Australia, has recently announced that its anti-cancer drug CYT997 has begun a Phase II clinical trial for the treatment of relapsed or refractory multiple myeloma. Cytopia also announced that along with an upcoming Phase II clinical trial for the treatment of glioblastoma multiforme, they are presently conducting a feasibility analysis for a Phase II study of the compound for mesothelioma patients who have failed Alimta therapy—the only FDA-approved therapy for the treatment of pleural mesothelioma.

CYT997 is part of a new class of anti-cancer drugs known as vascular disrupting agents (VDAs), which target and attempt to disrupt the relationship between tumors and blood vessels. CYT997 is a VDA that possesses multiple mechanisms of action. The first mechanism of action involves shutting down the blood vessels that deliver nutrients and oxygen to the tumor, while the second mechanism directs and engages in general cytotoxic activities.

The compound that CYT997 is based on was discovered by researchers from Cytopia in 2003 and in 2005 the FDA accepted Cytopia’s application to begin a Phase I trial. The success of Phase I trials has led Cytopia to begin the Phase II trials introduced in this article.

Labels: mesothelioma

Source: BBC News

Reseachers from the Harvard Medical School have recently identifed the enzyme, known as pyruvate kinase, that allows cancer cells to consume the large amounts of glucose that are necessary for their growth and continued propagation. Pyruvate kinase comes in two distinct forms, but only one of the forms—the PKM2 form—enables the consumption of glucose at the rate necessary to sustain tumor growth. When reserachers learned how to knock out PKM2 production and force the enzyme into its other form, they discovered they could stop the growth of the cancerous cells. When they tested this therapy in mice, they found that tumorgenesis was significantly inhibited.

Reserachers have known that tumors consume large amounts of glucose since the pioneering work of Otto Warburn, a Nobel Prize-winning chemist, discovered this over seventy years ago, but until this discovery they have not been able to develop therapies based on the knowledge. PET Scans, one of the major imaging modalities used in cancer diagnostics, are used to identify body-wide tumor growth by using radioactive tracers to examine areas of accelarated glucose consumption. PET has been a hugely successful diagnostic technology and is one of the prime examples of how science has previously incorporated the knowledge of glucose consumption into medicine.

With this discovery, doctors are now hopeful that new treatments can be developed that will literally starve the cancer of glucose and, therefore, stop tumor growth altogther. While the researchers note that all the forms of cancer they looked at during their review exhibitd this enzyme, whatever treatments are created with it will almost certainly have to take into consideration the particular metabolic activity of the individual cancers. More research is certainly needed to confirm these findings, but it appears that the discovery of pyruvate kinase represents a real advancement in our knowledge of the bio-chemical processes that underlie cancerous growth.

Labels: cancer, mesothelioma

Source: Lung Cancer
(Roe OD, et al., Mesothelin-related predictive and prognostic factors in malignant mesothelioma: A nested case-control study, Lung Cancer (2008), doi:10.1016/j.lungcan.2007.12.025)

The search to discover and develop effective markers for mesothelioma is one of the most active areas of mesothelioma research. Doctors and scientists are engaged in a number of programs whose ultimate goal is the creation of simple and reliable tests that can indicate a patient’s disease status at any point in time. There are three major avenues this research is being carried out on: the development of markers for mesothelioma diagnosis, which would allow definitive diagnoses earlier in the disease’s staging, using less-invasive techniques; the development of markers for prognosis tracking and disease progression, which would allow treating physicians to evaluate the efficacy of a patient’s treatment and to make adjustments to it by analyzing the relationship between therapy and marker levels; and, finally, the creation of markers for screening purposes, where likely candidates for mesothelioma development, such as people with a history of asbestos exposure and their families, could under-go a simple test to indicate any underlying change in status possibly indicative of cancer development—much in the same way that people over 50 are recommended colonoscopies for screening of possible colon cancer or the development of precancerous lesions.

In the search for these markers, a number of possible targets have been proposed, but one of the most often studied is mesothelin, a membrane-bound glycoprotein of the mesothelium that previous studies have shown is significantly over-expressed in people with malignant mesothelioma, especially pleural mesothelioma and peritoneal mesothelioma, as well as certain other cancers. Mesothelin is considered to play an important role in cell adhesion, as well as in inter-cell signaling and recognition. Another avenue of marker research in the mesothelin family involves soluble mesothelin-related protein (SMRP), which can be found in serum and in the fluid from pleural effusions, as opposed to mesothelin which is bound to the cell’s surface.

An international team of researchers, including scientists and doctors from Norway, Australia and France, have recently released the results of a study that analyzed the efficacy of these mesothelin-related markers for use in the screening of mesothelioma, as well as their use for mesothelioma diagnosis, prognosis development and progression testing.

Overview of the Study

Previous studies on mesothelin expression and SMRP levels have both shown high sensitivity and specificity regarding mesothelioma diagnosis. One of the studies noted by the present authors suggested that SMRP could also be a screening marker, as that study found elevated SMRP levels one–five years prior to a mesothelioma diagnosis in a subset of asbestos-exposed indviduals.

Along with SMRP, other serum markers that have been proposed as markers for mesothelioma include CYFRA 21-1 (Cytokeratin Fragment 19) and CA125 (Cancer Antigen 125)—both of which have shown elevated levels in previous studies of the disease. The authors specifically noted that some previous studies had implicated CA125 in peritoneal metastasis. They included these markers in their analysis as well, both to compare with SMRP expression and to analyze these levels on their own.

To make their analysis, the authors identified forty-seven archival cases of confirmed mesothelioma where tumor samples and pre-clinical serum were still available for each of the patients. 29 of these cases were identified as pleural mesothelioma, seven as peritoneal mesothelioma and there was a single diagnosis of mesothelioma of the tunica vaginalis, an exceedingly rare form of the disease. Histologically, the cases of pleural mesothelioma were split between 33 cases of epitheloid mesothelioma and 6 cases of bi-phasic mesothelioma. All of the peritoneal cases presented as epitheloid mesothelioma, while the tunica vaginalis case presented as bi-phasic mesothelioma. The levels of SMRP, CYFRA 21-1 and CA125 were then compared to a control group of 121 healthy adults. Mesothelin expression was examined only in the cases of confirmed mesothelioma.

The results of the pre-clinical serum marker tests showed no significant differences between the control group and the mesothelioma group in terms of mean marker levels, which led the authors to conclude that these markers should not be used as part of a screening process. They also noted that much more research needs to be completed in this area before a definitive conclusion can be delivered.

In 36 of the 47 mesothelioma cases (77%), mesothelin was expressed in more than 50% of the identified tumor cells. Three cases did not show any mesothelin expression, five showed expression in less than 25% of malignant cells and three showed expression between 26% and 50%. When mesothelin expression was identified in the bi-phasic cases, it was only in the epitheloid component, as the sarcomatous component in the mixed subtype always returned an expression value of zero. The authors did not find any correlation between mesothelin expression in tumors and SMRP levels in their pre-clinical serum samples.

The authors also divided the mesothelioma cases into two groups: those with mesothelin expression greater than 50% in tumor cells and those with less. Patients in the higher mesothelin expression group had a longer median survival figure at twelve months than did those in the less than 50% subgroup, which showed a median figure of only six months. When they compared mean survival between the pleural mesothelioma group and the peritoneal mesothelioma group, they found that the pleural group’s overall mean survival was eleven months, while the peritoneal group’s mean figure was forty-five months—a substantial difference indicative of the peritoneal disease’s typically enhanced prognosis. Further analysis showed that the peritoneal group highly expressed mesothelin in all its cases, while the pleural group did so in less (75%). Within the epithelial pleural subgroup, they correlated high mesothelin expression with a better prognosis as well.

These findings have led the authors to propose that mesothelin expression is not a marker of disease progression, but is in fact a marker of disease differentiation, so patients presenting with high mesothelin expression may reflect a disease subtype with a better prognosis due to less aggressive malignant behavior.

Conclusion

The authors conclude their paper stating that the serum markers they analyzed—SMRP, CA125 and CYFRA 21-1—were not recommended for use as screening markers. Further investigation into each marker, especially the relationship between mesothelioma, peritoneal metastasis/progression and CA125, is warranted by their expression by the disease, but their use as screening markers should be avoided. They also state that their hypotheses on mesothelin expression call for further research to confirm this behavior, as well as to explain its biological component.

Labels: mesothelioma

Source: CancerCell.org

One of the most exciting areas of current mesothelioma research is the growing body of knowledge that has been discovered about the disease’s molecular and genetic foundations. Even though much of this research is still quite preliminary, doctors and scientists are successfully—albeit, slowly—adding to our understanding of the precise mutations responsible for the development of mesothelioma. A systematic understanding of the relationship between these various mutations has, however, not yet been developed. One of the important precursor steps in creating a cohesive model of human mesothelioma genesis is the development of a mouse model that properly accounts for the disease’s genesis and progression. Not withstanding the significant genetic and biological differences between mice and humans, the fact remains that many of the greatest successes in human medicine have been guided by results obtained from murine testing.

Researchers from the Netherlands have recently published an article that describes their development of a conditional mouse model for mesothelioma carcinogenicity. Their results were obtained through testing of mice bred with specific mutations. Through their analysis of the correlations between individual gene mutations and malignant behavior, they’ve drawn specific conclusions regarding the manner in which individual mutations are responsible for the development, behavior and progression of mesothelioma.

What follows is a summary of their findings.

Overview of the Study

As we have previously covered in these news updates, mesothelioma is one of the most difficult of all forms of cancer to treat effectively. In its most common form, pleural mesothelioma, it typically presents only in the disease’s later stages and almost universally with a poor prognosis. Peritoneal mesothelioma, the second most-common form of the disease, typically presents with a less aggressive behavior pattern and a longer-term median survival range, but neither form responds well to conventional cancer treatments. Because of this, the development of new treatment modalities takes on greater and greater importance. Gene therapy represents one of these promising new strategies, but the lack of specific models regarding the disease’s growth pattern has limited the creation of effective medicine with it. Now that the Dutch researchers have published their findings, many members of the mesothelioma research community will be looking at their results with great interest to see what they reveal about possible treatment targets.

Individual studies have separately reported on a number of genetic mutations that have been implicated in mesothelioma genesis. Mutations and subsequent dysfunction of the tumor suppressor genes INK4A and P14ARF have been previously been reported on, as have loss and mutation of NF2 and TRP53. The authors note that Ink4a/ARF and TRP53 play well-known roles in cell-cycle regulation, while reduced NF2 expression “lowers cell adhesion and induces Schwann cell proliferation, whereas enhanced expression of NF2 leads to growth arrest.” A number of other genes have also been proposed as conducive to mesothelioma development, but the genes mentioned above have received the most attention.

To develop their model, the researchers bred a number of mice families with mesothelial-specific mutations to the Nf2, p53 and Ink4a pathways so they could chart the effects that each of these mutations, both singularly and in combination with the other mutations, had on the development of mesothelioma in these mice. Their findings were indicative of the importance these genes play in mesothelioma carcinogenicity.

One of the first things the researchers studied was the role these mutations had on tumor growth in the first place. They reported that the mice developed a number of individual tumors, but mesothelioma was the single most common development. The most common origin sites for it were the visceral pleuras of the lung and heart, while the most common metastatic developments included the parietal pleura, the diaphragm and the thoracic chest well.

When they looked at the individual relationships between gene mutation and malignant events, they discovered that individual losses of NF2, p53 or Ink4 were all clearly indicative of mesothelioma genesis, but that the loss of all three often led to the development of the most aggressive behavior patterns in their sample. The average latency period (the time between the mice’s first exposure to asbestos and their development of mesothelioma) for mice presenting with NF2;p53 loss was 135 days and for mice with NF2;Ink4a/Arf loss it was 220 days, while the latency period in mice who exhibited loss of NF2;p53;Ink4A was only 80 days. All of the most aggressive epitheloid and sarcomatoid mesotheliomas,i.e., those that were invasive of both the visceral and the parietal pleura, were found in this same NF2;p53;Ink4A group, while mice in the NF2/p53 or NF2;Ink4a/Arf groups did not exhibit the same aggressive behavior. Because of this, the researchers conclude that the loss of Ink4a (especially Ink4a alone-not Ink4a/Arf) leads to the most aggressive malignancies.

The relationship of NF2 and p53 loss to mesothelioma development was also covered extensively in the paper, where the authors conclusively state the importance of these mutations to disease development and progression. The authors propose that exposure to asbestos directly leads to a number of damaging genetic events (“genotoxic effects”), such as loss of both NF2 and Ink4a/Arf, which they see as the origin of asbestos’ carcinogenicity. If their hypothesis is correct, this could be the beginnings of our understanding of the precise physical relationship between asbestos exposure and mesothelioma development.

With NF2 playing such an important role in the development of the disease, the authors wonder if therapies utilizing NF2 re-expression would be effective for the treatment of mesothelioma. They note that recent research on NF2 re-expression has demonstrated some experimental efficacy for inhibiting cell proliferation and impairing the spread and invasive potential of certain types of cells.

The authors discuss a number of other novel findings in the genesis of mesothelioma. We have only covered a small number of their findings in this summary, so we recommend interested readers to read the full article to learn more about this newly developed mouse model.

Conclusion

The development of this mouse model should spur further research into the genetic mutations that underlie mesothelioma development. A greater understanding of the interrelationship between these mutations is sure to shed significant light on the cellular behavior of the disease, which will—hopefully—lead to the development of more targeted and effective therapies.

Labels: mesothelioma

Source: Duluth News Tribune

Minnesota’s Iron Range is an area where taconite and other forms of iron ore have been mined for generations. Epidemiological research over the previous few years has shown that miners in this area have developed mesothelioma at a much higher rate than the national average and many questions have been raised as to why this is. Taconite is a form of low-grade iron ore, but it is not an asbestos mineral, which is the only conclusively shown cause of pleural mesothelioma, as well as the other forms of the disease. A number of studies on standard taconite have confirmed that it does have an asbestos-like form, but that it is conclusively not an asbestos-mineral and, therefore, should not present with the same risks of exposure as does asbestos. However: the rate of mesothelioma in the Iron Range has generated new questions about taconite exposure and now the University of Minnesota is seeking funding for a number of studies on this question.

Officials from The University appeared before the Minnesota House to request $4.9 for the studies, which are expected to take of five years. $4.1 million will be devoted to the actual completion of the studies and $800,000 will be devoted to air quality testing in the area.

University health officials said that some of the questions the study seeks to answer will include: What was the actual cause of death of the approximately 70,000 miners employed in the state’s taconite mines between the 1950s to the 1980s. Is there a link between health conditions and the time spent in the miners? What—if anything—was the difference in harmful material exposures between the 58 miners who died of mesothelioma and those who didn’t develop the cancer?

All who are involved and aware of the situation support the commencement of the studies. The funding is sure to be received, but the manner in which it is approved will likely be the major negotiation. The findings are already early awaited by many people, but are most eagerly awaited by the miners and their families, as what can be understood about the exposures of the previous generations is likely to protect the lives and well-being of the younger miners who are just entering the industry today.

Labels: mesothelioma

Source: Industrial Health 2007, 45, 787-792

As awareness of the hazards of asbestos exposure became more common during the last few decades, many developed nations implemented statutory protocols strictly regulating the manner in which asbestos could be commercially used. Some of these nations even moved past regulation and enacted outright bans on the use of asbestos-family minerals. However, this pattern has not been duplicated among developing nations, where the use of asbestos has often continued unabated. Safety procedures that are necessary to protect the health of the work force have not been implemented in many of these nation’s factories and without active regulatory enforcement there is rarely any monitoring of air quality levels. The result is that workers continue to operate in unsafe environments where they are regularly exposed to extremely high levels of a known carcinogen, conclusively shown to cause all forms of mesothelioma, especially the two most common forms of the disease: pleural mesothelioma and peritoneal mesothelioma, as well as lung cancer and asbestosis.

In order to understand the exposure risks in these kinds of factories, Iranian researchers collected air samples from a brake lining manufacturing plant in Iran and compared their findings to the permissible exposure limit (PEL) regarding asbestos exposure developed and currently utilized by the Occupational Safety and Health Administration (OSHA).

Overview of the Study

The authors state that Iran has 26 brake lining manufacturing plans in current operation and the total workforce employed in those plants is approximately 3,000 people. They selected one of these plants to study overall air quality levels and to analyze the exposure risks of specific manufacturing processes. In selecting the lining manufacturing plant, the authors described some of the tasks performed, which included the grinding, beveling and drilling of materials, as well as a number of other procedures. Many of these tasks are dry processes, where the materials at hand release large amounts of dust into the air.

In measuring overall airborne dust samples, the authors found an average of particle concentration of 9.6 mg/m³, with the highest levels found in workers employed in the beveling process: 16.32 mg/m³. While the average figure is just below the threshold limit of 10 mg/m³ per day for total dust set by the American Conference of Governmental Industrial Hygienists, the bevellers, as well as those responsible for polish (11.40 mg/m³) and reassembly (11.54 mg/m³) found the particle density in their air exceeding ACGIH’s limits. OSHA’s threshold limit for this test is 15 mg/m³ , so the bevellers exceeded that limit as well.

To analyze the asbestos density in the plant’s breathable air, the authors used phase contrast optical microscopy (PCM), which is the standard technique for asbestos testing. The results returned showed an average fiber concentration of .78 f/cc, with the highest recorded level at 1.85 f/cc. With OSHA’s PEL (permissible exposure limit) for asbestos density set at only 0.1 fibers/cc, the average concentration level was 7.8 times greater than OSHA’s recommendation.

The authors completed their study in the summer, when ventilation was at its most effective, as the plant’s windows were all open because of the summer heat. The authors speculate that dust and asbestos levels during winter months would be much greater than the levels they measured because windows wouldn’t be open during winter, so ventilation would be less effective.

Conclusion

The results of the study clearly indicate asbestos and dust levels greater than OSHA recommendations. These levels also clearly indicate a heightened exposure risk for asbestos-related diseases, such as mesothelioma and lung cancer. In describing their paper as the first to look at asbestos levels in a brake lining manufacturing plant in Iran, the authors also see it as representative of asbestos levels found in plants in most developing countries. They strongly recommend improvements in ventilation and housekeeping to reduce contaminant levels.

Labels: asbestos

Source: Clinical Cancer Research

Full Title: “Sensitive and Specific New Enzyme-Linked Immunosorbent Assay for N-ERC/Mesothelin Increases its Potential as a Useful Serum Tumor Marker for Mesothelioma”

The early diagnosis of mesothelioma is a crucial element in achieving the best prognosis. If the disease is discovered in its beginning stages it can be treated with aggressive tri-modal therapy, which may extend a person’s life significantly beyond the typical range of mesothelioma survivors. The problem, however, is that mesothelioma is difficult to diagnose in the early stages. It shares many common symptoms with less serious conditions and often goes undiagnosed until its more serious effects arise during the disease’s advanced stages. Diagnoses are also missed because the diffuse malignancy pattern typical of standard-form pleural mesothelioma means the cancer’s growth is often overlooked or not even rendered by imaging technologies during the disease’s earliest stages. What is needed—and is sorely lacking—is the development of a simple test that can easily return a diagnosis or at least an indication that mesothelioma may be at work.

A variety of research projects are actively working on just this issue, with the development of tumor makers specific to mesothelioma among the most important. A tumor marker is a diagnostic tool that can be used to easily test for the presence of a particular malignancy in the blood of patient or in a tissue sample not otherwise indicative of cancer. A number of markers have been proposed for mesothelioma diagnosis and researchers around the world are busy looking for the most effective ones. In 2006, a group of doctors and researchers from Japan proposed the use of N-ERC/mesothelin as another potential tumor marker for malignant pleural mesothelioma. These researchers have recently published an update to their original work that describes the development of an improved enzyme-linked immunosorbent assay (ELISA) system with a higher sensitivity and specificity for the detection of N-ERC/mesothelin in a blood sample.

Overview of the Study

To study the diagnostic value of N-ERC/mesothelin and the efficacy of their improved ELISA system, the authors enrolled 293 patients into their study. 39 patients presented with histologically-confirmed mesothelioma, 201 with an asbestos-related illness that was not mesothelioma, 45 with lung cancer and 8 with other malignancies. A group of 102 healthy people were used as a control group.

To establish baseline N-ERC/mesothelin levels, the authors first analyzed the group of healthy patients, who showed generally uniform levels without any statistically significant differences based on sex or smoking status, although there was some correlation between older patient age and increased N-ERC/mesothelin levels.

When the authors moved to the study of the mesothelioma group, they found significant correlation between this group and high N-ERC/mesothelin levels. Median levels for the mesothelioma cohort were significantly greater than the levels found in all other patient groups. They found that within this cohort, patients who presented with epitheloid mesothelioma demonstrated especially high levels. They also discovered a correlation between higher N-ERC/mesothelin levels and advanced stage disease. All of these results clearly point to the continued study of N-ERC/mesothelin as a tumor marker for mesothelioma.

Conclusion

It is hoped that the development of specific tumor markers will enable more diagnoses of early stage mesothelioma—a time when the disease appears much more responsive to therapy than it does in its later stages. The authors noted an article by David Sugarbaker that said patients who received aggressive tri-modal therapy during the early stages of the disease demonstrated a 5-year survival figure exceeding 40%. For a disease known mainly for its poor prognosis, a demonstration of 5-year survival figures is truly a cause for hope.

The authors conclude the paper stating that their use of N-ERC/mesothelin and the improved ELISA system has demonstrated clear diagnostic value and they call for more research into potential tumor markers. While confirmation of their findings must be made by independent researchers before we can definitively establish the efficacy of their system, everyone agrees that the development of a simple blood test for mesothelioma is one of the great goals of current mesothelioma research. Such a development would truly revolutionize the manner in which the disease would be treated, as patients could begin therapy much sooner than they currently do.

Labels: mesothelioma

Source: European Journal of Cardio-Thoracic Surgery

Mesothelioma is an aggressive malignancy that primarily attacks the pleural surfaces surrounding the lungs, although it can also attack the peritoneum and—in rare cases—the pericardium and the mesothelial tissue surrounding the male reproductive system. Its normal behavior pattern is characterized by a diffuse spread of malignant cells throughout an entire surface area, where the boundaries between cancerous and non-cancerous tissues are blurred and often break down—making surgical resection of the cancer extremely difficult, if not impossible. This pattern is in marked contrast to other forms of cancer that present as locally-invasive, individually-identifiable tumors that evidence a clear boundary between the tumor and the otherwise healthy surrounding tissue.

Within the last decade, however, articles describing a number of cases that depart from this behavior pattern have appeared in the literature. These articles describe cases of histologically-proven pleural mesothelioma where individuals presented with locally-invasive pleural tumors that did not show any sign of diffuse spread and were more amenable to surgical resection than is the standard form of pleural mesothelioma. While these findings show a clear need for more research, its extreme rarity has limited researchers’ abilities to learn more about it. There are less than 100 proven cases of what is now known as localized malignant pleural mesothelioma in the literature, so large-scale studies of this subclass are currently impossible. Our knowledge of the disorder is anecdotal at best and is entirely based on journal descriptions of individual cases and presentations. Researchers from the United Kingdom have recently added to the literature on localized malignant pleural mesothelioma with an article that describes their experience with ten cases over an eight-year period.

What follows is a summary of their article.

Overview of the Study

The authors of the study work in the Department of Thoracic Surgery at Glenfield Hospital in Leicester, UK. During an eight-year period they performed surgery for 218 patients with pleural mesothelioma—10 of whom presented with the localized subtype under discussion here. These ten patients were all males and the median age at presentation was almost 66 years old. All had pathologically-confirmed malignant pleural mesothelioma. In terms of the histological subtypes of their diagnoses: four of the patients presented with epitheloid mesothelioma, four with sarcomatoid mesothelioma and two with the bi-phasic subtype. They all underwent surgery to remove a locally-invasive tumor that had infiltrated at least the chest wall: six presented with right-side infiltration and four with left-side infiltration. All patients underwent some form of pleurectomy: seven patients received a subtotal parietal pleurectomy, while the other three received a total parietal pleurectomy.

The results of the surgery were statistically much better than the results obtained after surgery for standard-form pleural mesothelioma. There were no deaths within 30 days of the surgery, although two needed drainage for post-surgery pleural effusions. The authors report microscopically complete resection in two patients and macroscopically complete resection in the remaining eight. Two patients died within one year of surgery (one at three months and one at ten months) and two more showed progression of the disease, but they were still alive during the period of the study. The authors report median survival at 56 months, which is much longer than the median survival range of 8–16 months typically reported for standard pleural mesothelioma. They also note that the longest survivor in their cohort was still alive at 70 months post surgery—a very rare occurrence for mesothelioma patients.

Conclusion

The authors concur with the previously published literature that localized malignant pleural mesothelioma has a distinctly different behavior pattern than does the standard-form disease. Using locally aggressive surgery, they were able to achieve some form of complete resection in all ten patients and their median survival figure of 56 months is quite a bit longer than anything reported in the literature on standard-form pleural mesothelioma. However, they are quick to note that a sample size of only ten cases isn’t nearly large enough to draw any definitive conclusions from and they call, as do most doctors who’ve had any experience with this rare malignancy, for more research into its biology and overall behavior.

Labels: mesothelioma

Source: Respirtory Medicine (2008) 102, 328-331

Imaging is one of the essential technology frameworks used in cancer diagnosis in general and for the diagnosis of mesothelioma in particular. Scientists have developed a number of different technologies that provide doctors with the tools to diagnose cancer, treat it and to track one’s progress in fighting it. While these tools are not perfect and have not cured cancer in toto, their successes cannot be discounted and it is not hyperbole to say that these imaging systems have truly revolutionized the practice of medicine in the United States and around the world. However, not all imaging technologies are created equal, nor can they be applied interchangeably. Each individual system has its own set of strengths and weaknesses and part of the job of doctors and researchers is to discover the strengths of the technology and maximize its use towards those ends, while also identifying its weaknesses and minimizing or stopping its use in scenarios that can exploit those weaknesses.

The imaging of pleural masses, such as those found in pleural mesothelioma, represents an especially important area of research as it requires as much precision as possible in the use of the available modalities. Because of the structure of the tissues involved, however, it can be difficult to return scans with high enough resolution to definitely determine a diagnosis. Because of this, doctors and researchers are actively studying which imaging modalities are the most effective for making certain kinds of diagnoses. It is within this light that doctors from the Ohio State University Medical Center in Columbus, Ohio have recently released a summation of their use of the standard imaging technologies in their diagnoses of pleural masses.

Introduction to the Study

The doctors compared the efficacy of the following imaging technologies for the diagnosis of pleural masses: chest radiography (chest x-ray), computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET). The doctors noted both the strengths and weaknesses of each system and made specific recommendations regarding the applicability of the technology for particular uses. While pleural mesothelioma remains the most feared of pleural malignancies, there are other malignancies which require imaging precision for the development of a definitive diagnosis as well.

Chest Radiography (X-Ray)

X-rays are the oldest and most commonly used imaging technology in medicine. An x-ray is frequently the first diagnostic test used by a doctor when pulmonary issues are suspected, but it’s rarely the final one in the diagnosis of pleural masses as its results are limited by poor resolution and it is not generally effective in the differentiation between benign and malignant tissue.

Computed Tomography (CT)

For the diagnosis of pleural issues, CT is a markedly superior technology to x-ray. Not only can CT better distinguish pleural disease from lung parenchymal (the functional tissues in the lungs, such as alevoli and alveolar duct) disease, but it is more adept at determining the location and extent of disease, detecting chest wall invasion and identifying pleural plaques.

Magnetic Resonance Imaging (MRI)

While CT has become the standard imaging technology for the diagnosis of pleural masses, MRI represents an improvement upon CT in a number of ways. It provides an image with superior soft tissue contrast, as well as superior spatial resolution, and this allows it to be even more sensitive to chest wall invasion or the invasion of adjacent tissues by cancerous cells than is CT. This latter facility is important in the staging of disease and in developing a resection strategy before surgery. However, MRIs cost has made it prohibitive for some of these purposes and its limited availability in certain areas has also restricted the number of people who can undergo it.

Positron Emission Tomography (PET)

PET is the newest of the modalities under discussion. While it has shown an ability to recognize individual tumors in the body and to show the results of distant metastases, its use for the diagnosis of pleural masses is limited because it’s not as effective as CT or MRI in showing chest wall or diaphragmatic infiltration.

Conclusion

The techniques discussed in this article all serve important medical functions and their applicability or inapplicability to the diagonosis of pleural masses should not be seen as invalidating their general use. As we said above, each of the technologies have their own strengths and weaknesses and the key is to maximize the use of these strengths and to minimize their use when their weaknesses impact their diagnostic value. CT remains the standard of care for most imaging involving pleural masses, but MRI does show improvements upon CT in a number of ways. With diseases such as pleural mesothelioma continuing to attack the lives of people, these technologies all serve important functions in the quest to keep patients healthy.

Labels: mesothelioma

Source: Duluth News Tribune

The Federal Mine Safety Health Administration (MSHA) has recently announced new rules governing airborne asbestos levels in mines across the country, finally bringing the mining industry into the same asbestos regulatory levels as are industries that are covered by OSHA standards.

The new rules lower the allowable fiber concentration in regular minespaces from two fibers per cubic centimeter to 0.1 fibers per cubic centimeter—a 95% reduction in the allowable density of fiber concentration. The rules also lowered the allowable limit at which workers can briefly be exposed to higher concentration levels. The previous rules stated that brief exposures could as high as 10 fibers per cubic centimeter for up to 15 minutes, while the new rules state that exposures can only occur with concentrations up to 1 fiber/cc for 30 minutes.

The rules changes were long fought-for by miners’ advocates and were actually first proposed in 1999 by the U.S. Department of Labor, which is MSHA’s parent organization. While no asbestos is mined in the U.S. these days, there have been a number of cases where the ore from certain mines was found to have some kind of asbestos contamination. The vermiculite mine in Libby, Montana is probably the most famous example of this kind of contamination, but other examples also exist. There are currently a number of studies being conducted in the State of Minnesota to analyze the high numbers of mesothelioma cases, mainly pleural mesothelioma, that are found among the State’s Iron Range workers—none of whom work with directly with asbestos, but who may have been exposed to the mineral in contaminated taconite mines. The new MSHA guidelines were designed to protect miners from these kinds of situations.

Richard E. Stickler, acting assistant secretary of labor for mine safety and health, has said,

“This final rule will help improve health protection for miners who work in an environment where asbestos is present...Furthermore, it will help lower the risk of material impairment of health or functional capacity over a miner’s working lifetime.”

Labels: asbestos

Extrapleural Pneumonectomy, IHOC Cisplatin and Gemcitabine With Amifostine and Sodium Thiosulfate Cytoprotection for Resectable Malignant Pleural Mesothelioma

RATIONALE: After removal of visible cancer in the chest, chemotherapy drugs are used to kill or stop tumor cells from dividing, so that they stop growing or/and die. Cisplatin is currently used safely as in intra-operative treatment for malignant pleural mesothelioma. This study is aimed to determine if the addition of gemcitabine as a second intracavitary chemotherapy can be accomplished safely...

Date First Received: December 10, 2007

Last Updated: December 20, 2007

Verified by: Dana-Farber Cancer Institute, December 2007

Clinical Trial Phase: Phase 1 | Start Date: November 2007

Overall Status: Recruiting

Estimated Enrollment: 36

Brief Summary

Official Title: “A Phase I Trial of Extrapleural Pneumonectomy, Intrathoracic/Intraperitoneal Hyperthermic (IOHC) Cisplatin and Gemcitabine With Intravenous Amifostine and Sodium Thiosulfate Cytoprotection for Patients With Resectable Malignant Pleural Mesothelioma”

Condition Keyword(s):

• Malignant Pleural Mesothelioma

Intervention(s):

• Procedure: Extrapleural pneumonectomy (EPP)
• Drug: cisplatin
• Drug: gemcitabine
• Drug: amifostine
• Drug: sodium thiosulfate

RATIONALE: After removal of visible cancer in the chest, chemotherapy drugs are used to kill or stop tumor cells from dividing, so that they stop growing or/and die. Cisplatin is currently used safely as in intra-operative treatment for malignant pleural mesothelioma.

This study is aimed to determine if the addition of gemcitabine as a second intracavitary chemotherapy can be accomplished safely.

PURPOSE: This is a Phase I trial to study the efficacy of combination chemotherapy consisting of gemcitabine and cisplatin administered in the operating room and put into the chest and abdomen for one hour. We are also looking at the effects of heating the chemotherapy to a temperature of 42 degrees Celsius and the effect of cytoprotection agents: amifostine and sodium thiosulfate to counteract potential side effects of chemotherapy.

Study Type: Interventional

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

Detailed Clinical Trial Description

- This is a dose escalation study of gemcitabine with a fixed dose of cisplatin - Patients will undergo surgery with Extrapleural Pneumonectomy, which entails the removal of the inner and outer lining of the lung (pleura) and the lung itself, including the lining overlying the pericardium and diaphragm. Resection of the pericardium and diaphragm are occasionally necessary to remove all visable tumor. This surgery is part of standard care for malignant pleural mesothelioma. - After surgery, a one hour lavage with heated cisplatin and or gemcitabine will be administered to the hemithorax (and abdominal regions if the diaphragm is no longer present). - Patients will remain hospitalized until they have recovered from surgery (usually 7-14 days). - Patients will return to the hospital during the first month after their surgery to be evaluated by the medical staff. - Dose escalation: 1) Three patients will be treated at the first dose level of gemcitabine. Labs will be monitored on a weekly basis, including a CBC, Chem-7, and LFT's. In the absence of developing dose-limiting toxicity (DLT) among the first 3 patients treated, dosages can be escalated. DLT will be defined as any grade 3 or higher renal toxicity, thrombocytopenia or other grade 3 toxicity not related to surgery 2) If none of these 3 patients have any toxicity, we will proceed to the next level of gemcitabine. 3) If DLT occurs in 1 of 3 patients at a given dose level, then 3 additional patients are added at that dose (for a total of 6 at this level)If no DLT occurs, we will proceed to the next level of gemcitabine. If DLT occurs in another patient, this dose is considered the maximum tolerated dose (MTD). 4) At any dose, 3 cases of DLT lead to discontinuation of recruitment at that dose and enrollment of 3 additional patients at a lower dose.

Outcome Measures for this Clinical Trial

Primary:

• To establish the maximally tolerated dose (MTD) of intraoperative Intrathoracic/Intraperitoneal hyperthermic gemcitabine and cisplatin combination modulated by amifostine and sodium thiosulfate in patients with malignant pleural mesothelioma. 2 years

Secondary:

• To determine and quantitate the safety of this combination in these patients by defining the dose limiting toxicity. 2 years
• To study the pharmacokinetics of gemcitabine and cisplatin combination administered in this way. 2 years

Criteria for Participation in this Clinical Trial

Inclusion Criteria:

• Histologically-proven diagnosis of stages I to III malignant mesothelioma of the pleura and negative mediastinal N2 lymph nodes (Malignancy is confined to the affected hemithorax)
• Adequate organ function including the following: adequate cardiac function, pulmonary function, renal and hepatic function and bone marrow reserve
• Adequate overall physical activity
• Surgical candidate for Extrapleural Pneumonectomy (EPP)

Exclusion Criteria:

• Extended disease outside the ipsilateral hemithorax as proven histologically, radiologically and/or intraoperatively
• Have received chemotherapy and or radiation therapy within the last 3 years at the time of study entry
• Serious concomitant systemic disorders
• Second active primary malignancy (to exclude non- melanoma skin cancer)
• Pregnancy at the time of the operation
• Psychiatric or addictive disorder which would preclude obtaining informed consent

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Brigham and Women's Hospital

Brigham and Women's Hospital

Boston Massachusetts 02115 United States

Overall Clinical Trial Officials and Contacts

David J Sugarbaker, MD Principal Investigator Brigham and Women's Hospital

Overall Contact: David Sugarbaker, M.D. 617-732-5004 dsugarbaker@partners.org

Additional Information

Information obtained from ClinicalTrials.gov on April 15, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00571298

Study ID Number: 07-091

ClinicalTrials.gov Identifier: NCT00571298

Health Authority: United States: Institutional Review Board

International Mesothelioma Program

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: ClinicalTrial

A Phase II Study of the Association of Glivec® Plus Gemzar® in Patients With Unresectable, Refractory, Malignant Mesothelioma

The purpose of this study is to evaluate the antitumor activity of a combination of Imatinib mesylate and Gemcitabine in patients with unresectable malignant mesothelioma expressing either PDGFR-beta or...

Date First Received: October 29, 2007

Last Updated: October 29, 2007

Verified by: Gruppo Italiano MEsotelioma, October 2007

Clinical Trial Phase: Phase 2 | Start Date: January 2008

Overall Status: Not yet recruiting

Estimated Enrollment: 56

Brief Summary

Official Title: “A Phase II Study of the Association of Glivec® (Imatinib Mesylate, Formerly Known as STI 571) Plus Gemzar® (Gemcitabine) in Patients With Unresectable, Refractory, Malignant Mesothelioma Expressing Either PDGFR-Beta or C-Kit”

The purpose of this study is to evaluate the antitumor activity of a combination of Imatinib mesylate and Gemcitabine in patients with unresectable malignant mesothelioma expressing either PDGFR-beta or C-kit

Study Type: Interventional

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

Detailed Clinical Trial Description

TITLE "A phase II study of the association of Glivec® (Imatinib mesylate, formerly known as STI 571) plus Gemzar® (Gemcitabine) in patients with unresectable, refractory, malignant mesothelioma expressing either PDGFR-beta or C-Kit"

PURPOSE Primary objective of the phase II ➢ Efficacy, i.e., response rate to study drugs

Secondary objectives of the phase II - Duration of response - Time to progression - Toxicity profile - Overall survival

PRIMARY VARIABLE The primary efficacy variable for the phase II part of the study is Best Overall Tumor Response, evaluated using the "Modified RECIST criteria for assessment of response in malignant pleural mesothelioma"

SECONDARY VARIABLES - Progression-free survival (PFS) form 1st administration onwards - Overall survival - Safety criteria, according to NCI-CTC criteria version 3.0

EFFICACY Objective tumor response assesed using the "Modified RECIST criteria for assessment of response in malignant pleural mesothelioma" SAFETY - Adverse events - Vital signs - Clinical and biohumoral findings

TREATMENT SCHEDULE - Gemzar 500 mg/m2, i.v., days 1 and 8 of a 21-days schedule, plus - Glivec 400 mg/die., per os

STATISTICAL DESIGN The study follows a two-stage design, according to the Simon model. We assume that with a response rate of 5% (H0) or less the drug is likely to be ineffective, and also, that, for the drug to be effective, a target response rate of 15% (H1) is required.

With a probability errors alfa of 5% and beta 20%, the calculated sample size is as reported in "PLANNED NUMBER OF PTS."

PLANNED NUMBER OF PTS. 23 or 56 patients, evaluable for efficacy. The number depends on the response rate. When 2 or more objective responses, i.e., CR or PR, are observed in the first 23 patients, the total number of patients will be increased to 56, otherwise the study will be stopped

STATISTICAL EVALUATION Efficacy and safety variables will be evaluated descriptively. Indeed, ORR estimates and its exact 95% confidence interval will be calculated. Kaplan-Meier method will be used to estimate duration of response, PFS and OS

DURATION OF TREATMENT All patients are scheduled to receive at least two cycles of chemotherapy unless there is unacceptable toxicity, progressive disease, or the patient requires or asks for withdrawal from the study Responding patients will receive treatment for 6 cycles or earlier if progression or unbearable toxicity Disease status will be re-evaluated every two cycles, using the same imaging procedures used at baseline, i.e., CT or NMR

INCLUSION CRITERIA - Age of > 18 years and <>

EXCLUSION CRITERIA - Co-existing tumors of different histologic origin, except non melanomatous localized skin cancer and/or in situ cervical carcinoma - A history of earlier tumors of different histologic origin being in complete remission since less than 5 years - Unresolved toxicity from prior antitumor treatment(s) - Primary peritoneal mesothelioma - Any of the following abnormal baseline hematological values: - Hb <> 2.5 mg/dL - ALAT and ASAT > 3 x UNL (unless due to liver metastases) - Serum creatinine > 1.5 mg/dL - Clinically relevant cardiovascular disease, i.e., myocardial infarction or other severe coronary artery diseases within the prior 6 months, cardiac arrythmia requiring medication, uncontrolled hypertension, overt cardiac failure or non compensated chronic heart disease in NYHA class II or more - History of psychiatric disabilities, potentially interfering with the capability of giving adequate informed consent - Pregnant or lactating women or inability/unwillingness to practice a medically approved method of contraception during study period (including 3 months following the end of treatment) - Uncontrolled active infections - Any condition which, in the judgement of the Investigator, would place the patient at undue risk or interfere with the results of the study

Outcome Measures for this Clinical Trial

Primary:

• Overall response rate Every two months

Secondary:

• Progression-free-survival; Overall Survival; Safety Follow-up after end of treatment will be every three months; safety will be analyzed throughout the whole study

Criteria for Participation in this Clinical Trial

Inclusion Criteria:

• Age of > 18 years and <>
• Patients with a histologically proven malignant mesothelioma of the pleura or of the peritoneum, expressing either PDFGR-beta or C-Kit by immunochemistry (ICH)
• Locally advanced disease, unsuitable for curative surgical resection, or metastatic disease
• Confirmed progression of the disease according to modified REcist-criteria, documented after a first-line, systemic (premetrex+cisplatin regimen) or local treatment (i.e., intrapleuric)
• ECOG Performance Status of 0, 1 or 2
• Life expectancy of at least 3 months
• Capability of understanding the objectives of the study and giving written informed consent
• Willingness and ability to comply with study requirements
• Sufficient caloric and fluid intake, including patients under enteral or parenteral nutrition

Exclusion Criteria:

• Co-existing tumors of different histologic origin, except non melanomatous localized skin cancer and/or in situ cervical carcinoma
• A history of earlier tumors of different histologic origin being in complete remission since less than 5 years
• Unresolved toxicity from prior antitumor treatment(s)
• Primary peritoneal mesothelioma
• Any of the following abnormal baseline hematological values:
• Hb <>
• WBC <>
• Neutrophils <>
• Platelets <>
• Serum bilirubin > 2.5 mg/dL
• ALAT and ASAT > 3 x UNL (unless due to liver metastases)
• Serum creatinine > 1.5 mg/dL
• Clinically relevant cardiovascular disease, i.e., myocardial infarction or other severe coronary artery diseases within the prior 6 months, cardiac arrythmia requiring medication, uncontrolled hypertension, overt cardiac failure or non compensated chronic heart disease in NYHA class II or more
• History of psychiatric disabilities, potentially interfering with the capability of giving adequate informed consent
• Pregnant or lactating women or inability/unwillingness to practice a medically approved method of contraception during study period (including 3 months following the end of treatment)
• Uncontrolled active infections
• Any condition which, in the judgement of the Investigator, would place the patient at undue risk or interfere with the results of the study

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Gruppo Italiano MEsotelioma

Medical Oncology, IRCCS San Matteo University Hospital Foundation

Pavia 27100 Italy

Overall Clinical Trial Officials and Contacts

Camillo Porta, MD Principal Investigator Medical Oncology, IRCCS San Matteo University Hospital Foundation, pavia, Italy

Overall Contact: Camillo Porta, MD +39-0382-501355 c.porta@smatteo.pv.it

Related Publications

References

Bertino P, Porta C, Barbone D, Germano S, Busacca S, Pinato S, Tassi G, Favoni R, Gaudino G, Mutti L. Preliminary data suggestive of a novel translational approach to mesothelioma treatment: imatinib mesylate with gemcitabine or pemetrexed. Thorax. 2007 Aug;62(8):690-5. Epub 2007 Feb 20.

Additional Information

Information obtained from ClinicalTrials.gov on April 15, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00551252

Study ID Number: GIMe/01/06

ClinicalTrials.gov Identifier: NCT00551252

Health Authority: Italy: Ethics Committee

Italian Mesothelioma Group Homepage

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: ClinicalTrial

Phase II Study of Bevacizumab, Pemetrexed and Carboplatin as First-Line Therapy in Malignant Pleural Mesothelioma

The primary objective is to assess antitumor activity of the combination of bevacizumab, pemetrexed and carboplatin, in terms of time to progression...

Date First Received: December 4, 2006

Last Updated: August 28, 2007

Verified by: Istituto Clinico Humanitas, August 2007

Clinical Trial Phase: Phase 2 | Start Date:

Overall Status: Not yet recruiting

Estimated Enrollment: 77

Brief Summary

Official Title: “Phase II Study of the Combination of Bevacizumab Plus Pemetrexed and Carboplatin as First-Line Therapy in Patients With Malignant Pleural Mesothelioma”

Condition Keyword(s):

• Mesothelioma

Intervention(s):

• Drug: bevacizumab
• Drug: pemetrexed
• Drug: carboplatin

The primary objective is to assess antitumor activity of the combination of bevacizumab, pemetrexed and carboplatin, in terms of time to progression.

Study Type: Interventional

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

Detailed Clinical Trial Description

Secondary endpoints are to evaluate: - the objective response rate (RR) of the combination; - the toxicity and the safety profile of the combination; - the duration of response (RD) and time to treatment failure (TTF); - the overall survival (OS)

Outcome Measures for this Clinical Trial

Primary:

• Time to progression (TTP) from first day of treatment until first observation of disease progression or death due to any cause or the last date the patient was known to be progression free or alive.

Secondary:

• Response rate (RR) assessed according to modified RECIST criteria for Malignant Pleural Mesothelioma.
• Overall survival (OS) computed as the time between the first day of treatment and the date of death or the last date the patient was known to be alive.

Criteria for Participation in this Clinical Trial

Inclusion Criteria:

• Histologically proven malignant pleural mesothelioma, inoperable, non previously treated with chemotherapy including intracavitary administration;
• PS 0-1;
• measurable and/or evaluable lesions according to RECIST criteria;
• adequate organ function.

Exclusion Criteria:

• uncontrolled hypertension;
• evidence of bleeding diathesis or coagulopathy;
• pregnancy or breast-feeding.

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Istituto Clinico Humanitas

Istituto Clinico Humanitas

Rozzano Milan 20089 Italy

Overall Clinical Trial Officials and Contacts

Armando Santoro, MD Principal Investigator Istituto Clinico Humanitas

Overall Contact: Armando Santoro, MD +39 02 8224 armando.santoro@humanitas.it

Related Publications

References

Ceresoli GL, Zucali PA, Favaretto AG, Grossi F, Bidoli P, Del Conte G, Ceribelli A, Bearz A, Morenghi E, Cavina R, Marangolo M, Parra HJ, Santoro A. Phase II study of pemetrexed plus carboplatin in malignant pleural mesothelioma. J Clin Oncol. 2006 Mar 20;24(9):1443-8.

Ceresoli GL, Chiti A, Zucali PA, Rodari M, Lutman RF, Salamina S, Incarbone M, Alloisio M, Santoro A. Early response evaluation in malignant pleural mesothelioma by positron emission tomography with [18F]fluorodeoxyglucose. J Clin Oncol. 2006 Oct 1;24(28):4587-93.

Additional Information

Information obtained from ClinicalTrials.gov on April 15, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00407459

Study ID Number: ONC-2006-003

ClinicalTrials.gov Identifier: NCT00407459

Health Authority: Italy: Ministry of Health

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: ClinicalTrial

A Study of VEGF-Antisense Oligonucleotide in Combination With Pemetrexed and Cisplatin for the Treatment of Advanced Malignant Mesothelioma

This will be a single institution non-randomized phase I/II trial for patients with malignant mesothelioma stage II and above, who have not received prior chemotherapy for their disease. The purpose of this phase is to select a dose of VEGF-AS (antiangiogenesis drug)to be given with standard doses of pemetrexed followed by cisplatin on day 1 of a 21-day cycle...

Date First Received: April 25, 2008
Last Updated: April 28, 2008
Verified by: Norris Comprehensive Cancer Center, April 2008
Clinical Trial Phase: Phase 1/Phase 2 | Start Date: April 2008
Overall Status: Not yet recruiting
Estimated Enrollment: 71
Brief Summary
Official Title: “A Phase I/II Study of VEGF-Antisense Oligonucleotide (VEGF-AS, Veglin) in Combination With Pemetrexed and Cisplatin for the Treatment of Advanced Malignant Mesothelioma”
Condition Keyword(s):
• Mesothelioma
Intervention(s):
• Drug: VEGF-Antisense Oligonucleotide , Pemetrex