Showing posts with label Mesothelioma type. Show all posts

Compare laboratory tests and imaging modalities utilized in the diagnosis of Mesothelioma.

What is the mortality rate for mesothelioma (localized and diffuse)?

Analyze the complications and prognosis for patients with Mesothelioma.

What is the incidence/prevalence of mesothelioma?

List and describe the four stages of mesothelioma, as described by the Butchart Staging System.

Explain the staging of mesothelioma.

Malignant pulmonary mesothelioma differentiated from bronchogenic carcinoma.

There are currently about 3000 new cases of Mesothelioma diagnosed per year, mostly in men over the age of 40.

The earlier mesothelioma is detected, the better your chances are for an effective treatment. To determine whether a person has mesothelioma, doctors may use one or more of these diagnostic methods:

• Chest X ray
• CAT scan - CT or Computerized Tomography
• MRI - Magnetic Resonance Imaging
• PET scan - Positron Emission Tomography
• PFT - Pulmonary Function Test
• Transbronchial biopsy - A flexible, lighted scope is passed down the trachea to the bronchi area of the lungs.
• Thoracotomy - During surgery, the chest is opened and examined, usually between two of the lower ribs on one side.
• Thoracoscopy - A thoracoscope with a video camera is sent through an incision between the ribs.
• Centesis - Pleural, peritoneal, or pericardial fluid is drained and evaluated. This technique is used both for diagnosis and to relieve pressure, pain, and fullness in the chest or abdominal areas.

Discuss the epidemiology and etiology of Mesothelioma

Patterns of failure following surgical resection for malignant pleural mesothelioma.

The optimum therapeutic strategy for patients with localized malignant mesothelioma continues to evolve. For patients who are eligible candidates, surgical resection plays an important role. An encouraging 45% 5-year survival rate has been reported for patients with early-stage disease who undergo EPP and have the favorable features of epithelial histology and the absence of mediastinal lymph node involvement.

Most patients present with more advanced disease, however, and the optimum local and systemic treatment for these patients has not been defined. No randomized trials evaluating the various surgical or adjuvant therapeutic approaches have been performed. Evaluation of treatment efficacy based on observed patterns of failure may suffer from treatment selection biases. Most studies also do not separate out the failure patterns based on the initial stage (clinical or pathologic) of the disease.

Consequently, it is difficult to discern the potential impact of a given adjuvant therapy. Given these limitations, however, some consistent observations from the available data can be made. For patients who undergo P/D, local recurrence (within the surgically operated hemithorax) is the most common form of recurrence. Efforts to decrease the chance of local recurrence after P/D have included the use of intrapleural and intravenous chemotherapy, brachytherapy, and external beam radiation therapy. None of these adjuvant treatment trials was randomized, and when compared with historical controls, none of the treatments used suggested a consistent outcome benefit. After P/D, the use of radiation is limited by the potential toxicity of the underlying organs, most importantly, the intact lung. Doses required to treat mesothelioma effectively are above the doses that would lead to damage to the lung parenchyma. Cisplatin and mitomycin have been used as agents have modest activity against mesothelioma. The doses of cisplatin used may not have been optimal, although they were based on prior pharmacokinetic studies.

Alternative approaches for patients who undergo P/D, such as the use of escalating doses of heated intrapleural cisplatin (given with a renal protecting agent, sodium thiosulfate, which provides the opportunity to deliver higher doses of chemotherapy), are being pursued by Sugarbaker et al. The availability of more active systemic chemotherapy agents or other intrapleural agents also may offer better therapeutic options for patients who undergo P/D.

Recently, Vogelzang et al presented the findings of a large randomized study that compared cisplatin/premetrexed to cisplatin and demonstrated an improvement in response rate (41% for cisplatin/pemetrexed versus 19% for cisplatin) and median survival (12.1 versus 9.3 months, respectively; P = 0.020). Other chemotherapy regimens with encouraging activity in mesothelioma include the combination of cisplatin and gemcitabine, with response rates ranging from 16% to 48%.

From a review of available data, patients with mesothelioma who have undergone P/D (with or without intrapleural chemotherapy) who are evaluated at the Dana Farber Cancer Institute and Brigham and Women's Hospital are offered therapy with systemic chemotherapy alone. After P/D, radiation is used only for palliative treatment. Patients who have undergone P/D are also appropriate candidates to receive chemotherapy or other novel therapeutic strategies being evaluated in clinical trials.

For patients who have undergone EPP, the pattern of recurrence is predominantly a combination of local and distant failure (Table 1). The local recurrence rates, however, seem to be lower than rates seen after P/D. This observation may represent a shift of the natural history of the disease. Metastatic mesothelioma is often seen late in the course of the disease, but it may become the dominant source of disease after aggressive local surgical management.

Many studies define abdominal recurrence as a site of distant recurrence, although this may represent transdiaphragmatic extension of the pleural mesothelioma. Advances in local therapy also may decrease the rate of abdominal recurrences. True distant recurrences (bone, central nervous system, contralateral hemithorax) remain less common. The lowest rate of local recurrence (13%), with a 4% local-only recurrence rate, was seen in the study by Rusch et al, who used 54 Gy hemithorax radiation as adjuvant therapy. This is the lowest rate of local recurrence after an EPP that has been reported. Baldini et al reported a 50% local recurrence rate, with a 13% local-only rate, after trimodality therapy.

One possibility for the differences between these two reports is the lower dose of radiation (30.6 Gy) used in the latter study. In the study by Rusch et al, distant failures predominate, and the patients are appropriate candidates for systemic chemotherapy, which could be administered either as neoadjuvant or adjuvant therapy. Kestenholz et al currently are performing a phase II clinical trial of neoadjuvant cisplatin and gemcitabine administered for three cycles followed by EPP and adjuvant radiation therapy.

A similar approach also is being pursued in an ongoing clinical trial using neoadjuvant cisplatin/pemetrexed for four cycles before EPP followed by 54 Gy of adjuvant hemithorax radiation. Alternatively, patients who have undergone EPP could be treated with adjuvant chemotherapy in addition to adjuvant radiation therapy.

Currently, patients evaluated at the Dana Farber Cancer Institute and Brigham and Women's Hospital who have undergone EPP are offered adjuvant chemotherapy followed by hemithorax radiation to 54 Gy in an effort to maximize local and distant control rates. Further clinical studies are needed for all patients with mesothelioma to define the optimum surgery and duration and types of adjuvant therapy. The appropriate multimodality approaches most likely will differ based on disease stage, histology, and patient performance status. intrapleural chemotheraphy treatments.

Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pennsylvania Medical Center, Philadelphia 19104, USA. sterman@mail.med.upenn.edu

Advances in the treatment of malignant pleural mesothelioma.

Malignant pleural mesothelioma is a neoplasm that is commonly fatal and for which there are no widely accepted curative approaches. Mesothelioma is unresponsive to most chemotherapy and radiotherapy regimens, and it typically recurs even after the most aggressive attempts at surgical resection. Multimodality approaches have been of some benefit in prolonging survival of very highly selected subgroups of patients, but they have had a relatively small impact on the majority of the patients diagnosed with this disease. As the incidence of pleural mesothelioma peaks in the United States and Europe over the next 10 to 20 years, new therapeutic measures will be necessary. This review will discuss the roles of chemotherapy, radiotherapy, surgery, and combined modality approaches in the treatment of pleural mesothelioma, as well as scientific advances made in the past decade that have led to the development of experimental techniques, such as photodynamic therapy, immunotherapy, and gene therapy, that are currently undergoing human clinical trials. These promising new avenues may modify the therapeutic nihilism that is rampant among clinicians dealing with mesothelioma.

Treatment of malignant pleural mesothelioma

In Japan, it is predicted that mesothelioma will rapidly increase in the future. Malignant pleural mesothelioma that accounts for approximately 90% of mesothelioma as a whole has a median survival time of approximately nine months which is considered a poor prognosis. As for the treatment of this disease,extrapleural pneumonectomy or pleurectomy/decortication are available for those patients who can be surgically operated on. However, since a complete cure rate is low when only surgical treatment is performed, generally a multimodality treatment is performed wherein chemotherapy and/or radiotherapy are combined. For chemotherapy, a large-scale randomized phase III study demonstrated that a treatment using two agents: pemetrexed, which is a new multitargeted antifolate, and cisplatin is effective. Pemetrexed will be the drug of first choice for mesothelioma in the future. As other treatment methods, chemohyperthermia, treatments using various kinds of cytokines and angiogenesis inhibitors, genetic treatment and photodynamic therapy have been attempted. The current treatment results for this disease are very poor, and there has been a strong demand for establishing an effective treatment method.

Peritoneal mesothelioma: treatment approach based on natural history.

A more modern treatment strategy for diffuse malignant peritoneal mesothelioma may be suggested (figure 3). Clinical suspicion of diffuse malignant mesothelioma (peritoneal carcinomatosis) calls for laparoscopy with evaluation of parietal and visceral peritoneum and multiple biopsies sufficient for definitive histologic diagnosis. Cytologic examination of ascitic fluid is not likely to be of benefit. CT of chest, abdomen, and pelvis is needed for evaluation of visceral involvement and the presence of distant metastases. Contrast enhancement of the gastrointestinal and urinary tract is necessary with the CT. Additional radiologic techniques for detection of distant metastases should be used if there are clinical or laboratory signs of extraperitoneal spread. After histologic diagnosis and extent of tumor spread have been documented, and if no symptoms of intestinal obstruction are present, the patient may be subjected to two to three courses of induction intraperitoneal chemotherapy. This will provide the clinician with important information on tumor response to chemotherapy, minimize tumor accumulation on bowel surfaces, and provide time for surgical conditioning. The time devoted to induction chemotherapy will allow occult distant metastases to be detected. In patients with a response or stable disease, cytoreductive surgery is attempted approximately 2 months after completion of induction chemotherapy. Surgery must be aimed at achieving complete or near-complete cytoreduction through the use of peritonectomy procedures [46,47]. Additional intraperitoneal chemotherapy should be administered intraoperatively and in the early postoperative period (figure 3). This treatment strategy may be the most feasible one according to existing knowledge of the natural history of diffuse malignant peritoneal mesothelioma. Only further phase II clinical trials can reveal the extent to which it is beneficial. Because of the rare occurrence of this disease, the quickest answer would come as a result of cooperative study by several groups experienced in these treatment modalities.

At Risk Jobs and Locations

It is inhalation of asbestos fibers which can cause mesothelioma or asbestos lung cancer. Even low exposure levels of the tiny fibers or asbestos dust are very dangerous. After the 1980's workplace exposure to asbestos became more rare, but it can take up to 40 years for signs of mesothelioma asbestos lung cancer are noticed.

Most patients were exposed to asbestos fibers on the job or in the workplace in what is known as occupational exposure. Another form of exposure is called paraoccupational exposure. This form of asbestos exposure can be harder to determine the source, but it is usually contracted by a family member of someone who has been exposed in the workplace.

Typically the family member is exposed to asbestos dust or fibers from the worker's clothing, and when the clothing is handled the dust is released and inhaled. Family members that are exposed in this way, may be exposed to smaller amounts, but are still very much at risk.

In the same way, those that have homes or work work near facilities that have asbestos may also be at risk even though there is not obvious direct contact. The fine asbestos dust can easily be carried by the wind over long distances.

In the past, some of the industries that could have been a source of asbestos were factories, shipyards, power plants, oil refineries, steel manufacturing plants, and any company or job site involved with construction or the removal of old building materials. Often the demolition of buildings that contain asbestos can release the dust into the environment, and trucks hauling the materials can further spread the fine asbestos fibers.

Likewise, people who live near these types of sites likely to have asbestos around the facility are also at risk: refineries, power plants, factories, shipyards, steel mills and building demolition are types of work sites that can release asbestos fibers into the environment and contaminate nearby residential neighborhoods.

Trades:

* Manufacturing of asbestos products (insulation, roofing, building, materials)
* Vehicle repair (brakes & clutches)
* Construction workers and contractors
* Maritime workers
* Miners and drillmen
* Offshore rust removals
* Oil refinery workers
* Power plants
* Railway workers
* Sand or abrasive manufacturers
* Shipyards / ships / ship builders
* Steel mills
* Tile cutters

Occupations:

* Auto Mechanics
* Boiler makers
* Bricklayers
* Building Inspectors
* Carpenters
* Drywallers
* Electricians
* Floor Coverings
* Furnace Workers
* Glazers
* Grinders
* Hod carriers
* Insulators
* Iron workers
* Laborers
* Longshoremen
* Maintenance workers
* Merchant marines
* Millwrights
* Operating Engineers
* Painters
* Plasterers
* Plumbers
* Roofers
* Sand blasters
* Sheet metal workers
* Steam fitters
* Tile setters
* Welders
* United States Navy veterans
* Welders

Many occupations have an increased risk for developing lung cancer. For example, asbestos insulation workers have 92 times the risk of developing of lung cancer, and smelter workers have 3-8 times the risk of developing lung cancer. The risk of lung cancer is also increased in people who work in the manufacturing of certain industrial gases, pharmaceuticals, soaps and detergents, paints, inorganic pigments, plastics, and synthetic rubber. The risk of developing lung cancer is related to the amount of exposure to the cancer-causing agent.

For example, the risk of lung cancer in humans is proportional to the number of cigarettes smoked. The risk of developing lung cancer is 8-20 times greater in smokers compared to people who have never smoked. A smaller, but real risk exists for cigar and pipe smokers. Some lung cancer causing agents react together to significantly worsen the risk of developing cancer. The combined exposure to asbestos and tobacco smoke clearly multiplies the risk of developing lung cancer.

The risk of lung cancer is greater for those living in urban areas. This risk is approximately 1.2 to 2.3 times that of people living in rural areas. There is also an increased risk of lung cancer in smokers whose close relatives have had lung cancer. Scarring in the lungs from previous infections or injury can be associated with and increased risk of cancer.

Alimta for Mesothelioma

There are a number of mesothelioma treatments that can be used to help treat the symptoms of Mesothelioma and to deal with this illness. While there is no cure for mesothelioma, other methods can be used to help lengthen the expected lifespan of the person afflicted with the disease.

Alimta is a drug that has been used to help stop the rapid growth of mesothelioma cancerous cells within your body. This drug was brought about during 2004 and, since then, it has been helping patients that have Mesothelioma improve and stop the spread of this deadly disease. It has successfully helped patients live longer and happier lives just by taking Alimta. This particular medication has undergone careful and rigorous scrutiny successfully, which has allowed it to be approved by the FDA.

Alimta does more than simply work well for Mesothelioma - this drug has also been used to treat other various cancers. It has helped particularly well in lung cancers, among others and has starkly improved the quality of treatment that cancer treatments can receive since 2004. It can also be very helpful to anyone who is already taking other medications for their mesothelioma as Alimta can be combined with other treatment options.

While Alimta is not going to completely make your Mesothelioma go away, it will halt the progress of any cancerous cells within your body. This is why Alimta is a perfect to use as a medication because people that have mesothelioma may not have long to live. Once they have been diagnosed with Mesothelioma, most patients with the cancer are not likely to survive very long once the symptoms start to show. Hence, Alimta has been extremely helpful to people who are suffering from Mesothelioma - Alimta helps by halting the progress of the cancer, allowing the patient to live a longer and more fulfilled life than they normally could have.

Commonly, another drug that often goes well with Alimta is Cispltain, which is another form of cancer fighting medication. Often, Cisplatin is used in combination with Alimta because these two cancer-fighting agents complement themselves well when working to fight off mesothelioma. This is one element where two medications can be used in combination with each other to improve the health of a patient with Mesothelioma.

If you are wondering how the new drug Alimta will help you, then you should know that this cancer fighting medication could work for you in helping to destroy cancerous cells. Alimta actually works on the cancer cells themselves, decreasing their ability to grow at their natural rate. This actually provides you with less cancer cells in your body, which will give you a longer life but without this medical assistance you could be left with the 6-12 months that people who are diagnosed with mesothelioma have. Alimta has been tested and proven to help patients who are suffering with mesothelioma and this medication is currently being tested on other cancers to try to stop the growth of other cancerous diseases.

Your doctor should know several things before treating you with Alimta. It is important that you tell your doctor if you have any previous medical problems. In most cases, they will run you through a rigorous pre-screening process. Your doctor will want to know everything possible about both your full medical history and the medical history of your family before you start treatment for Alimta.
Make sure that you tell the doctor if you are allergic to any medications, even though a doctor should have your full medical chart. There are may be instances when not all allergies that you have are written down and getting this sorted out is important prior to starting the treatment. If the doctor gave a patient a medication that he or she was allergic to, that patient could get sick or even die from this allergic reaction. It is also a good idea that, prior to taking Alimta, the doctor be well informed of a complete and exhaustive list of each of the medications that you take, how frequently, and how much at a time, including both prescribed and over the counter medications. This will help the doctor make sure that Alimta will not have a bad side effect with another one of your medications that you are currently taking.

Alimta is not a simple medication to take. It is far more than just taking a pill with some water. In this particular treatment, specific guidelines must be followed in order to have a successful treatment. Before taking Alimta, it is important to also take two other supplements with this medication, Vitamin B-12 and folic acid. The combination of these two supplements with the medication can create the best possible beneficial situation for the patient. These supplements are taken primarily because there is also a chance of a small skin inflammation after you first start taking the Alimta. Make sure to ask your doctor in which way you could lower the chance of having this outbreak, it is recommended that your doctor should put you on a steroid to lessen the chance of a bad skin reaction when taking Alimta.

The side effects of any medication are important to be aware. Hence, you should know all of the side effects of any medication prior to deciding to use it as a treatment for your cancer. Most cancer medications have a wide list of side effects, but that is because all of these cancer-destroying medications work on killing the cancerous cells within your body. It is quite frequent that these medications will also damage healthy cells, which is why there is such a chance for side effects. A few of the side effects that Alimta has are loss of hunger, sores inside the mouth, rashes throughout the body, exhaustion, depression, general weakness, and other similar side effects. These may sound bad, however it is much preferred that a patient deal with such minor side effects in order to extend his or her life. The benefits outweigh the risks.

Mesotheliona Clinical Trials

In order to one day find a mesothelioma cure, doctors engage in clinical trials where they test new mesothelioma drugs to determine the if they are effective.

Mesothelioma clinical trials follow a plan of very strict scientific guidelines, which is called a protocol. The protocol explains everything that will happen in the study. It must be approved by review boards made up of health care professionals and other qualified people before the study can enroll patients.

When a potential mesothelioma drug is first identified, preclinical studies, which are conducted in a laboratory setting, help to find out whether the drug is safe to test in humans. During this stage, the drug is usually studied in animals to answer questions about how a drug works and how the body changes and disposes of it. Humans do not participate in preclinical studies. There are four possible phases of cancer clinical trials in humans, each designed to answer different questions about the treatment being studies.

In Phase I mesothelioma clinical trials, doctors are primarily studying the safety of giving mesothelioma drugs to humans, while also looking for the best way to give a medication (for example, as a pill, an injection, or an infusion). They will usually study how the mesothelioma drug is eliminated from the body in humans. Also, doctors are trying to find the right doses for further testing. They carefully watch for any side effects. Phase I study drugs are usually given to small groups of humans. During this phase, for drugs used to treat mesothelioma cancer, investigators may be able to find out which tumors a treatment works best in.

In Phase II mesothelioma clinical trials, the mesothelioma drug is studies in a larger group. The primary purpose of these studies is to see how well the drug or treatment shrinks tumors in patients with specific types of cancer. The investigator will watch closely for side effects and will also watch how the disease responds to the treatment.

In Phase III mesothelioma clinical trials, the new cancer treatment is generally compared to a standard existing treatment. Patients are usually randomly assigned (that is, a process similar to flipping a coin is used to determine which treatment the patient receives) to receive either a standard treatment or the new treatment. During the trial, patients may or may not be told which treatment they are getting but are told what to expect and what to watch for. Occasionally, even the doctor will not know which treatment each patient is getting so that he or she can remain unbiased about how the disease is responding to the treatment. (This is uncommon in cancer clinical trials). Phase III studies are designed to ensure that any side effects that patients experience are identified treated according to local standards of care.

Phase IV mesothelioma clinical trials study a drug that has already been approved by the Food and Drug Administration. Drug companies often sponsor these trials to study even more uses of drugs already available

Clinical Trials: Mesothelioma

California

Duarte; City of Hope National Medical Center
A Double-Blind Placebo Controlled Randomized Phase II of Gemcitabine & Cisplatin With Or Without the VEGF Inhibitor Bevacizumab in Patients with Malignant Mesothelioma

San Diego; Sharp Clinical Oncology Research
ONCONASE ® plus doxorubicin vs. doxorubicin for patients with Malignant Pleural or Peritoneal Mesothelioma who have had no more than one prior chemotherapy regimen.

Colorado

Aurora; Research Center
ALIMTA Plus Gemcitabine (Gemzar) for Patients with Malignant Pleural or Peritoneal Mesothelioma who have not had previous chemotherapy

Aurora; University of Colorado Cancer Center
ONCONASE ® plus doxorubicin vs. doxorubicin for patients with Malignant Pleural or Peritoneal Mesothelioma who have had no more than one prior chemotherapy regimen.

Florida

Miami; Oncology / Hematology Group of South Florida
ONCONASE ® plus doxorubicin vs. doxorubicin for patients with Malignant Pleural or Peritoneal Mesothelioma who have had no more than one prior chemotherapy regimen.

Tampa; Research Center
ALIMTA Plus Gemcitabine (Gemzar) for Patients with Malignant Pleural or Peritoneal Mesothelioma who have not had previous chemotherapy

Illinois

Chicago; Research Center
ALIMTA Plus Gemcitabine (Gemzar) for Patients with Malignant Pleural or Peritoneal Mesothelioma who have not had previous chemotherapy

Chicago; University of Chicago Medical Center, Section of Hematology / Oncology
ONCONASE ® plus doxorubicin vs. doxorubicin for patients with Malignant Pleural or Peritoneal Mesothelioma who have had no more than one prior chemotherapy regimen.

Indiana

South Bend; Northern Indiana Cancer Research Consortium
ONCONASE ® plus doxorubicin vs. doxorubicin for patients with Malignant Pleural or Peritoneal Mesothelioma who have had no more than one prior chemotherapy regimen.

Maryland

Baltimore; Research Center
ALIMTA Plus Gemcitabine (Gemzar) for Patients with Malignant Pleural or Peritoneal Mesothelioma who have not had previous chemotherapy

Massachusetts

Boston; Research Center
ALIMTA Plus Gemcitabine (Gemzar) for Patients with Malignant Pleural or Peritoneal Mesothelioma who have not had previous chemotherapy

Michigan

Grand Rapids; Spectrum Health, Cook Research Department
ONCONASE ® plus doxorubicin vs. doxorubicin for patients with Malignant Pleural or Peritoneal Mesothelioma who have had no more than one prior chemotherapy regimen.

New Jersey

Somerville; Somerset Medical Center
ONCONASE ® plus doxorubicin vs. doxorubicin for patients with Malignant Pleural or Peritoneal Mesothelioma who have had no more than one prior chemotherapy regimen.

New Mexico

Albuquerque; Research Center
ALIMTA Plus Gemcitabine (Gemzar) for Patients with Malignant Pleural or Peritoneal Mesothelioma who have not had previous chemotherapy

New York

New York; Columbia-Presbyterian Medical Center
ALIMTA Plus Gemcitabine as Front-Line Chemotherapy for Patients with Malignant Pleural or Peritoneal Mesothelioma. A phase II Clinical Trial.

New York; Columbia-Presbyterian Medical Center
Open - Label Study of Alimta (pemetrexed) Combination with Cisplatin for Chemonaive Patients with Malignant Pleural Mesothelioma.

New York; Research Center
ALIMTA Plus Gemcitabine (Gemzar) for Patients with Malignant Pleural or Peritoneal Mesothelioma who have not had previous chemotherapy

New York; Columbia Presbyterian Medical Center
ONCONASE ® plus doxorubicin vs. doxorubicin for patients with Malignant Pleural or Peritoneal Mesothelioma who have had no more than one prior chemotherapy regimen.

New York; Columbia University Medical Center
A phase II, open-label, non-randomized, multicenter, single agent study of intravenous sdx-102 for the treatment of patients with MTAP - deficient cancers.

New York; Columbia-Presbyterian Medical Center
Phase II trial of combined resection, intraperitoneal chemotherapy, and whole abdominal radiation for treatment of peritoneal mesothelioma.

New York; Columbia-Presbyterian Medical Center
Phase II trial of perioperative gemcitabine and cisplatin chemotherapy in resected pleural mesothelioma

New York; Biomedical Research Alliance of New York
Cancer in the Lungs- Caused by exposure to asbestos

Oklahoma

Tulsa; Southwestern Regional Medical Center
Open-Label Study of ALIMTA (pemetrexed) and Cisplatin in chemonaive patients with malignant Pleural Mesothelioma.

Texas

Austin; Lone Star Oncology Consultants, PA
ONCONASE ® plus doxorubicin vs. doxorubicin for patients with Malignant Pleural or Peritoneal Mesothelioma who have had no more than one prior chemotherapy regimen.

Houston; S. R. Burzynski Clinic
Phase II Study Of Antineoplastons A10 And AS2-1 In Patients With Mesothelioma

Wisconsin

Madison; Research Center
ALIMTA Plus Gemcitabine (Gemzar) for Patients with Malignant Pleural or Peritoneal Mesothelioma who have not had previous chemotherapy

International

D-14109 Berlin, Germany; Pneumologie II, Zentralklinik Emil von Bering
ONCONASE ® plus doxorubicin vs. doxorubicin for patients with Malignant Pleural or Peritoneal Mesothelioma who have had no more than one prior chemotherapy regimen.

D-21075 Hamburg, Germany; Allgemeines Krankenhaus Harburg
ONCONASE ® plus doxorubicin vs. doxorubicin for patients with Malignant Pleural or Peritoneal Mesothelioma who have had no more than one prior chemotherapy regimen.

D-22927 Grosshansdorf, Germany; Krankenhaus Grosshansdorf, Zentrum fur Pneumologie und Thoraxchirurgie, Pneumo.- Onkolog. Abteilung
ONCONASE ® plus doxorubicin vs. doxorubicin for patients with Malignant Pleural or Peritoneal Mesothelioma who have had no more than one prior chemotherapy regimen.

D-81675 Munchen, Germany; TU Munchen, Klinikum Rechts der Isar, Med. Klinik Hamatologie und Onkologie
ONCONASE ® plus doxorubicin vs. doxorubicin for patients with Malignant Pleural or Peritoneal Mesothelioma who have had no more than one prior chemotherapy regimen.

D-82131 Gauting, Germany; Asklepios Fachkliniken, Zentrum fur Pneumologie und Thoraxchirurgie
ONCONASE ® plus doxorubicin vs. doxorubicin for patients with Malignant Pleural or Peritoneal Mesothelioma who have had no more than one prior chemotherapy regimen.

Alessandria, Italy; Azienda Osped. Nazion Antonio e Biagio e Cesare Arrigo, Divisione di Pneumologia
ONCONASE ® plus doxorubicin vs. doxorubicin for patients with Malignant Pleural or Peritoneal Mesothelioma who have had no more than one prior chemotherapy regimen.

Genova, Italy; Struttura Semplice di Pneumotisiologia, Ospedale San Marino
ONCONASE ® plus doxorubicin vs. doxorubicin for patients with Malignant Pleural or Peritoneal Mesothelioma who have had no more than one prior chemotherapy regimen.

Pavia, Italy; IRCCS - Policlinico San Matteo, Clinica Malattie dell Apparato Respiratorio
ONCONASE ® plus doxorubicin vs. doxorubicin for patients with Malignant Pleural or Peritoneal Mesothelioma who have had no more than one prior chemotherapy regimen.

Pavia, Italy; IRCCS - Policlinico San Matteo, Divisione di Pneumologia
ONCONASE ® plus doxorubicin vs. doxorubicin for patients with Malignant Pleural or Peritoneal Mesothelioma who have had no more than one prior chemotherapy regimen.

Venezia, Italy; Ospedale Civile di Venezia, Unita Operativa Oncologia Medica
ONCONASE ® plus doxorubicin vs. doxorubicin for patients with Malignant Pleural or Peritoneal Mesothelioma who have had no more than one prior chemotherapy regimen

General Information / Anatomy / Function / Statistics

• Mesothelioma are tumours originating from the lining of the body cavities; this includes the chest and abdomen. Although the most common type of mesothelioma begins within the chest, this cancer should not be confused with lung cancer. Mesotheliomas arise from the serosal lining outside of the lungs within the chest or outside the bowel within the abdomen.
• About 100 new cases of malignant mesothelioma appear in Canada each year
• 30-40 cases are seen at the BC Cancer Agency each year
• Malignant mesothelioma is usually not curable

Symptoms / Signs

• Symptoms and signs from mesotheliomas depend upon location of the mesothelioma, its size and whether it is benign or malignant
• Benign forms of the disease are generally asymptomatic
• The symptomatology of malignant mesotheliomas is due to tumour growth resulting in invasion of surrounding structures and/or the production of fluid (pleural effusion, ascites, or pericardial effusion). Chest pain may be caused by invasion of the chest wall. Pleural effusion causes collapse of adjacent lung and shortness of breath.
• Symptoms of distant spread are possible, but uncommon since the tumour is usually a local problem and blood borne spread is uncommon
• Patients with more advanced disease may be ill generally with fever, night sweats and weight loss
• Involvement of the membrane around the heart (pericardium) may cause heart rhythm disturbances

Etiology / Carcinogens / Risks

• There is a definite association between asbestos and mesothelioma. The risk associated with asbestos exposure has been shown by many investigators and inhalation of asbestos poses the most serious hazard.
• In approximately 30% of mesotheliomas, no asbestos exposure can be traced
• Crocidolite (Cape blue asbestos), the main cancer causing form of asbestos, is associated with over 90% of pleural and peritoneal mesotheliomas. Other types of asbestos fibre have been associated in a less significant way.
• Individuals at highest risk are those employed in the asbestos industry; dockyard workers, especially if they dismantle asbestos-insulated steam piping; those who handle and manufacture asbestos compounds; insulators and steam fitters; and those in demolition and construction industries
• Spouses and children of asbestos workers are also at risk
• The latent interval between exposure to asbestos and development of tumour is long (15-25 years)
• Mesothelioma is not caused by cigarette smoking but asbestos exposure and cigarette smoking both increase the risk of lung cancer

Prevention

• The only method of prevention is avoidance of asbestos exposure
• Cigarette smoking should be avoided by all persons and asbestos exposed individuals should avoid cigarette smoke in particular because asbestos plus cigarette smoking can cause lung cancer

Diagnosis / Screening / Staging / Grading / Types

• The chest X-ray is a very helpful test, usually showing thickening of the pleura or pleural effusion in patients with pleural mesothelioma. Sometimes a CT scan of the chest may be required for further information.
• A pleural biopsy is essential for pathological confirmation of the disease. Although pleural fluid cytology may be abnormal, this is often difficult to interpret.
• Patients having peritoneal mesothelioma may require an abdominal surgery for exploration of the peritonial surfaces and biopsy of any lesions observed

Types

• Mesotheliomas may be of epithelial or sarcomatous. Sarcomatous types are more malignant and tend to be resistant to treatment.

Treatment

• Treatment unsatisfactory with no recent advances
• Malignant mesotheliomas are serious illnesses and cure of the disease is rare
• Survival with this type of cancer obviously varies with the extent of the disease, but overall it is in the region of one year

Surgery

• Because of the large area of pleural surfaces, complete surgical removal is rarely technically feasible. The advisability of resection is always considered at diagnosis, but only a small minority of cases are eligible for an attempted resection. Spread of disease to the chest wall, heart, or esophagus often rules out the possibility of an operation.

Radiation

• Radiation may be given for control of symptoms in a localized area. Radiation therapy does not have the power to cure this disease. Radiation cannot be given to the entire tumour because this would involve the treatment of large volumes of normal tissue and the dose of radiation required for tumour control is too high for this to be tolerated. Radiation can, however, be of value in controlling pain in a localized area.

Chemotherapy

• Benefits from chemotherapy treatments for mesothelioma are uncertain as the tumour is often resistant. The best available treatment programs do not have the power to cure any patients with mesothelioma. 20% of patients may have a temporary shrinkage of the disease with currently available drugs.

General Support and Symptom Control

• If pain is associated with mesothelioma, good drug prescriptions are available that can control this. Pleural effusions (fluid build up) can be treated by a small surgical procedure that removes the fluid, permitting re-expansion of the lung and improvement in shortness of breath. Some patients with mesothelioma may have very slow growing tumours and if symptoms are not present, it is often advisable to follow the patient with regular chest X-rays without specific therapy. When symptoms do occur, they should be assessed on an individual basis.
• Chemotherapy may be considered for treatment of recurrent thymoma

Treating Malignant Pleural Mesotheliomas: An Uphill Climb

Introduction

Malignant pleural mesothelioma (MPM) seems to be on the increase worldwide and especially in the United States, with 2000 to 3000 new cases reported annually. Individuals who have been exposed to asbestos carry a 20% lifetime risk for acquiring MPM; smoking exacerbates the disease.

As MPM is a universally fatal cancer at present, with patients dying from pulmonary complications and infections, more effective treatment strategies are desperately needed. A somber series of presentations at the 9th World Conference on Lung Cancer in Tokyo suggested, however, that no potential breakthrough treatments seem to be on the horizon. Indeed, as the presentations suggested, there still is no standard treatment regimen for MPM.

Theories of Negativity

Triple Combination: Methotrexate (MTX) Plus Interferon Alpha and Gamma

Dr. Ola Brodin, from South Hospital, Stockholm, Sweden, reviewed results from a phase 2 multicenter Northern European trial in which patients received triple combination therapy, consisting of high-dose MTX, alpha interferon, and gamma interferon.^[1] Previously, single institutional trials reported response rates of 37%, 12%, and 24% for single-agent high-dose MTX, interferon alpha, and interferon gamma, respectively. The investigators designed this study to ascertain whether the 3 agents together would behave synergistically, or at least prove to be additive, as a previous in vitro Finnish study had suggested that MTX and interferon alpha behaved in a synergistic fashion.

MTX 3000 mg, followed by leucovorin rescue every 2 weeks, with interferon alpha 3 million units subcutaneously on days 3 to 8, and interferon gamma 40 mcg on days 3, 7, and 11 were given for 3 cycles every 2 weeks. Patients who showed responses were then given 3 more courses of therapy every 3 weeks at lower doses. Most patients (27) received all 6 planned cycles, whereas 4 patients received 5 cycles, 2 patients received 4 cycles, 7 patients received 3 cycles, and 3 patients received only 1 cycle.

A total of 49 patients were enrolled, but 6 were not included in the final analysis, because 4 patients were not treated, 1 was found to have peritoneal disease, and an additional patient had been previously treated. Among the 43 treated patients, 39 were evaluable. The overall response rate of 19% consisted of 8 partial remissions (PRs). There were 22 patients (51%) with stable disease and 9 patients (21%) with progressive disease. Median survival time was 15 months, with longer survival seen among those patients achieving a PR. Toxicity was primarily hematologic, with 4 grade 3 neutropenias noted. Rather than enhance the effect of the other drugs, it seems that this triple combination led to competition among the various compounds, resulting in a worse response rate than with each agent used separately. The investigators concluded that interferon would not be included in the development of future chemotherapy combination strategies for treatment of MPM.

Vinorelbine plus Oxaliplatin

A second combination approach, combining vinorelbine and oxaliplatin, was reviewed by Dr. Jeremy Steele of the London Lung Cancer Group.^[2] Building on previous data in which a 20% to 25% response rate was achieved with single-agent vinorelbine in the treatment of poor-prognosis MPM,^[3] Dr. Steele and colleagues from St. Bartholomew's Hospital in London paired oxaliplatin with vinorelbine. A total of 21 patients were given vinorelbine 30 mg/m² on days 1 and 8 with oxaliplatin 130 mg/m² on day 1 every 3 weeks for a total of 6 cycles. Seventeen patients have completed treatment while 4 continue on therapy. To date, only 2 partial responses (11.8%) were seen, with stable disease in 13 (76%) and progressive disease in 2 patients. Toxicity was significant, with 61% grade 3 and 4 neutropenia. Phlebitis (9%) was the most common nonhematologic complication.

While this low level of activity was disappointing, Dr. Steele suggested that the low response rate might be due to the large number of stage 4 patients included in the study (62%), the higher proportion of less favorable histologic subtypes (sarcomatoid 33%, mixed 24%), as well as a higher proportion of performance status (PS)-2 patients (24%). Additionally, he suggested, it might be necessary to increase the dose of vinorelbine. For the present, oxaliplatin does not seem to contribute significantly to the treatment of MPM and should probably not be included in further clinical trials.

Weekly Vinorelbine Therapy

In a separate presentation, Dr. Steele updated last year's American Society of Clinical Oncology (ASCO) results on the weekly vinorelbine therapy mentioned before.^[4] A total of 64 patients, 64% with epithelioid tumors, 9% with sarcomatous tumors, and 27% with biphasic disease were given vinorelbine 30 mg/m² weekly for 6 weeks (constituting 1 cycle). A median of 2 cycles were administered (range 1-10), with 4 patients receiving ongoing treatments between cycles 4 and 6. Distribution by stage included 3% of patients in stage 1, 28% in stage 2, 28% in stage 3, and 39% in stage 4.

There were 12 PRs (21%), 36 patients (63%) with stable disease, and 9 patients (16%) with progressive disease. Quality of life, as measured by the Rotterdam Symptom Checklist, was enhanced significantly, with 49% of patients reporting improvements in lung-related symptoms, whereas 56% reported general physical improvements. Toxicity was primarily hematologic, with 63% asymptomatic grade 3 and 4 neutropenia, and an 18% incidence of neutropenic fevers. Other toxicities included phlebitis, malaise, anorexia, nausea, and vomiting, all reported in 12% of cases.

Dr. Steele concluded that use of vinorelbine correlated with significant improvements in quality of life, with acceptable toxicity and a respectable (20%+) response rate. He also suggested that this agent warrants further study with a best supportive care control arm. Postpresentation questioners were skeptical about the degree of improvement in patient quality of life and suggested that perhaps the mere fact that patients were seen on a weekly basis could account in large part for their enhanced well being. It was also suggested that the addition of pulmonary function studies would more accurately reflect the degree of response to treatment beyond chest x-rays and CT scans.

Gemcitabine Plus Cisplatin

J.W. van Haarst,^[5] from University Hospital Rotterdam in The Netherlands, reviewed data from a multicenter phase 2 trial that sought to validate a previous single institutional study that had reported a response rate of 48% in MPM with a combination of gemcitabine and cisplatin.^[6] Given as single agents, gemcitabine and cisplatin have shown response rates ranging from 7% to 14% in MPM, and in vitro studies have suggested a synergistic interaction between these 2 compounds.

Van Haarst and colleagues enrolled 32 patients with stage 2 through 4 MPM, 28 of which were stage 3 and 4. Histologically, 25 patients had epithelial tumors, 2 sarcomatous tumors, and 4 mixed tumors. Treatment consisted of gemcitabine 1250 mg/m² on days 1 and 8 with cisplatin 80 mg/m² on day 1. Cycles were repeated at 3-week intervals for a maximum of 6 cycles. A cohort of 25 patients was needed to render the study statistically significant, and a response rate of 20% or greater was needed to establish validity. Ten patients were not evaluable, 5 because they received less than 2 cycles of therapy and 3 because of toxicity. One patient refused treatment and another was lost to follow-up.

Of the 22 patients who were evaluable, only 4 (15%) had a PR. Median survival time was 10 months with a 1-year survival of 30%. There were 2 cases of leukopenias, whereas nonhematologic toxicities were insignificant. Because the observed response rate was less than 20%, the study did not meet its own standard for validity.

Dr. van Haarst speculated that the discrepancy between the single institutional trial results and this multicenter trial was likely due to differences in patient selection, treatment schedules, and methodology in evaluating treatment. Following the presentation, Dr. Byrne, the author of the single institutional study, noted that when a larger number of patients was eventually accrued (55), the response rate dropped from 48% to 32%.^[6]

Docetaxel

Two other studies failed to show any significant improvement over current therapies. The first, presented by Dr. Vorobiof from the Standton Oncology Centre in Johannesburg, South Africa, employed single-agent docetaxel among 31 patients with MPMs.^[7] Docetaxel 100 mg/m² was administered every 3 weeks with standard steroid pre- and posttreatment medication. Patients were evaluated with chest x-rays and CTs after every 3 cycles. Five patients were not evaluable, 3 having died within the first 2 weeks following the first cycle of chemotherapy, 1 from unknown causes, a second from toxicity while receiving alternative medications, and a third from progressive disease. A fourth patient refused treatment and a fifth was diagnosed incorrectly. Four more were not evaluable because treatment was ongoing.

Of the 22 patients who were evaluable, there were 3 PRs. Stable disease was observed in 11 and there were 6 minor responses (25% or less reduction in tumor burden). Median duration of response was longer for those who responded partially compared with those with stable disease (20 weeks vs 11 weeks). Median survival was a little over 12 months. Grade 3 and 4 toxicities included 4 patients with neutropenia, 4 with diarrhea, and 4 with mucositis. A majority of patients (13) experienced no toxic side effects. One individual from the audience pointed out that the results from this trial were less than encouraging, given that the response rate (10%) and the death rate (10%) were the same.

Cisplatin, Ifosfamide, and Mitomycin

Dr. Metinas, from Osmangazi University in Eskisehir, Turkey, reported on a single institutional trial on only 12 patients, that incorporated a control arm of 12 individuals.^[8] Among 16 patients treated with combination chemotherapy, consisting of cisplatin 90 mg/m² over 3 days, ifosfamide 2 g/m² over 3 days, and mitomycin 8 mg/m² on day 1, 4 were not evaluable due to inadequate follow-up. A partial response was seen in 3 patients, while 1 patient experienced tumor "regression," but deemed a minor response. The median survival time was 6 months for the patients who received chemotherapy vs 4 months for the 10 patients who received best supportive care alone. This difference was not statistically significant. Those patients with responsive or stable disease did have a longer and statistically significant median survival time (8.5 months) compared with those with progressive disease (3.5 months). The unusual feature about this trial was the fact that a control arm was established, a difficult proposition in most clinical settings.

Accentuating the Positive

Intrapleural Liposomal NDDP

Two additional presentations were interesting because they discussed new approaches to treat this MPM. Dr. Dong Shin and colleagues,^[9] from the M.D. Anderson Cancer Center in Houston, Texas, studied the intrapleural administration of a liposomal cisplatin analogue (L-NDDP) in 34 patients who were diagnosed with MPM and free-flowing pleural effusions. Various dose levels of L-NDDP were given intrapleurally, ranging from 250 mg/m² to 550 mg/m² every 3-4 weeks. The first 8 patients were treated at the time of thoracoscopy; 2 of them died after 1 and 3 courses of chemotherapy. Subsequently, the remaining patients were treated 1 week after catheter placement with no ensuing complications. Eleven patients were deemed not evaluable, 4 because of nontreatment and 7 due to loss of follow-up, leaving 23 evaluable patients.

Twenty-three patients had both and pre- and posttreatment biopsy samples available for analysis. No evidence of tumor could be found posttreatment in 13 patients (56%). Cytology samples were available in 18 pre- and posttreatment patient specimens, of which 15 (83%) had no evidence for residual tumor following treatment. Dose-limiting toxicity was pleuritic pain, as well as nausea and vomiting. Only 1 grade 4 neutropenia was observed, with 2 grade 3 thrombocytopenias, 1 grade 3 neutropenia, and 1 grade 3 anemia.

The author concluded that this approach was highly effective with an overall response rate of 33%. But he also acknowledged a colleague's assertion that this approach does not address the systemic nature of malignant mesotheliomas, making it unlikely to impact on overall survival. Moreover, so few patients would be able to benefit from this therapeutic modality, given the often widespread nature of disease at time of presentation. Currently, an ongoing phase 2 trial is looking at whether L-NDDP can be given preoperatively, followed by surgery, then radiation therapy.

Carboplatin Plus Pemetrexed Disodium

Dr. A. Calvert, from the Department of Medical Oncology at Newcastle-upon-Tyne, England, discussed the use of pemetrexed disodium (LY231514, MTA), a novel multi-targeted anti-folate that inhibits several folate-dependent enzymes, especially thymidylate synthase (TS).^[10] This phase 1 study enrolled from 3-6 patients at various dosing levels of pemetrexed disodium with carboplatin ranging from 400 mg/m² and area under the curve (AUC) 5, respectively. Pemetrexed disodium was given over 10 minutes intravenously on day 1, followed by infusion of carboplatin. Cycles were repeated every 21 days.

Among 29 enrolled patients with MPM, 27 were treated. Maximum tolerated dose of pemetrexed disodium was established at 500 mg/m². Of 25 patients evaluable for response, 10 achieved PRs (40%) and 15 demonstrated stable disease, all at various dose levels. No patient had progressive disease. Toxic effects were primarily myelosuppression with 60% leukopenia, neutropenia, and thrombocytopenia at the highest dose level. Most patients with grade 3 and 4 hematologic toxicities remained asymptomatic. Mild nonhematologic toxic effects included nausea, vomiting, asthenia, rash, and transitory elevations of liver transaminases. Furthermore, symptomatic improvement was documented in 14 cases, whereas CT scanning detected radiologic improvement in 10 patients. Patients received a median number of 6 courses of treatment. Median time to progression was almost 1 year, whereas median survival time was 410 days, a significant improvement over the 9-12 month survival of historic controls. Phase 2 trials with single agent pemetrexed disodium, as well as a randomized trial with pemetrexed disodium in combination with cisplatin, are currently ongoing.

Implications for Clinical Practice

Clearly, much work needs to be done before a standard treatment for MPM is defined. Until then, clinicians are urged to enroll such patients in randomized clinical trials whenever possible in order to further our understanding and refine our treatment approaches. Expanding our knowledge of the biology and molecular makeup of malignant mesothelioma will likely lead to more selective and specific therapies, even if more promising modalities remain elusive for the time being

Seeking Medical help

Mesothelioma can develop between 15 and 40 years or more after an exposure to asbestos. If you have been exposed to asbestos in the past and you start to suffer from any of the following symptoms you should visit your GP and mention your concerns:

* Pains in the lower back, abdomen or chest
* A persistent cough
* Breathing difficulties, shortness of breath or a feeling of tightness in the chest
* Rapid weight loss
* Problems with appetite or difficulty swallowing
* Sweating, fevers, diarrhoea or constipation
* Nausea or vomiting
* Swelling of the abdomen

Some people with mesothelioma have no symptoms at all in the early stages; therefore, if you know that you have been exposed to asbestos in the past and believe it may be the cause of your symptoms, it is always a good idea to visit a doctor for medical advice. Any damage caused by asbestos may be possible to detect with a scan or x-ray

Mesothelioma - Innovations in Treatment
Doctors and researchers are always on the lookout for new ways to treat malignant mesothelioma. The following innovations in treatment, while not a cure for malignant mesothelioma, show some promise in helping to treat the disease.

Mesothelioma - Alimta

Alimta, when given with another chemotherapy drug called cisplatin, is a chemotherapy drug recently approved by the FDA for the treatment of patients with malignant pleural mesothelioma.

Mesothelioma - Photodynamic Therapy

Photodynamic therapy uses special drugs and a special type of light to kill cancer cells during surgery. A drug that makes cancer cells more sensitive to light is injected into the patient’s vein several days before surgery. During surgery, a special light is used to locate the cancer. This treatment is being studied for early stages of malignant mesothelioma.

Mesothelioma - Immunotherapy

This type of treatment harnesses the power of the body’s own immune system. Immunotherapy is currently being researched as a treatment for malignant mesothelioma.

Mesothelioma - Gene Therapy

In studies of gene therapy for cancer, the goal is to improve the body’s natural ability to fight malignant mesothelioma directly or to make the cancer cells more sensitive to other kinds of therapy.

Mesothelioma - Brachytherapy

Brachytherapy is radiation therapy applied from within the body as opposed to from a machine outside the body. Radioactive sources are placed in or near the tumor, giving a high radiation dose to the tumor while reducing the radiation exposure in surrounding healthy tissues. This precision can help to minimize side effects.

Mesothelioma - Clinical Trials

A clinical trial (also clinical research) is a research study using human volunteers to answer specific health questions. Carefully conducted clinical trials help discover treatments that work in people and ways to improve health. Interventional trials determine whether experimental treatments or new ways of using known therapies are safe and effective under controlled environments. Observational trials address health issues in large groups of people or populations in natural settings. If you are interested in participating in a clinical trial, talk to your doctor about whether a clinical trial may be an appropriate option in your case.

Mesothelioma - Phase I

Phase I trials are considered the first step in testing the safety and efficacy of a new drug. Doctors and researchers are trying to determine many things about the drug’s effect on the disease and on the patient. Among the things that researchers are trying to determine are correct dosage, safety profile, and any side effects.

Mesothelioma - Phase II

At this stage, researchers select a relatively small group of patients to study the specific effects of the pre-determined dosage. Phase II studies also typically focus on a specific type of disease.

Mesothelioma - Phase III

During Phase III testing, researchers compare the effectiveness of the new, experimental drug against already existing therapies. Usually, patients are randomly assigned to therapeutic groups to cut down on the possibility of human bias. Phase III trials can be large, recruiting patients from across the country.