July 2010

MESOTHELIOMA TREATMENT OPTIONS

The treatment program for mesothelioma depends on many factors, including: the stage of the cancer, where the cancer is, how far the cancer has spread, how the cancer cells look under the microscope and the patient’s age and desires.

TIME MATTERS

People diagnosed with this disease are often told the expected survival time is only eight to twelve months. However, specialists in treating malignant mesothelioma at the leading cancer centers often have better statistics.

For instance, the five-year survival rate has approached 40% for selected patients of Dr. David Sugarbaker at Brigham and Women’s Center in Boston. To qualify for Dr. Sugarbaker’s treatment you must meet certain criteria. One of them is being in the early stages of the disease, so time is of the essence. To find out more about Dr. Sugarbaker and other physicians and cancer centers specializing in mesothelioma click on Finding Specialists.

Keeping track of your medical treatment is useful and a personal medical records file can help.

TRADITIONAL CARE

There are three traditional kinds of treatment for patients with malignant mesothelioma:

* Surgery (taking out the cancer)

* Chemotherapy (using drugs to fight the cancer)

* Radiation Therapy (using high-dose x-rays or other high-energy rays to kill cancer cells)

Often two or more of these are combined in the course of treatment. (NEW! Click here for the newest trial of trimodal lung-sparing treatment for pleural mesothelioma: The Columbia Protocol.)

MESOMARK BLOOD TEST

In January 2007, the Food and Drug Administration (FDA) approved the MESOMARK assay to help monitor response to treatment in epithelial and bi-phasic malignant mesothelioma patients. A specific protein, or biomarker, called Soluble Mesothelin-Related Peptide (SMRP), may be released into the blood by mesothelioma cancer cells. By measuring the amount of SMRP in a blood sample, doctors may be able to better monitor a patient's progress. Based on the limited amount of data currently available, use of this test may be beneficial, but effectiveness has not been determined at this time. The MESOMARK blood test has NOT yet been approved for the early diagnosis of mesothelioma.

This test has been approved as a Humanitarian Use Device (HUD), meaning that physicians must follow certain procedures to qualify their patients for testing. Once the physician is certified, informational brochures will be sent to be distributed to each applicable patient.

Those wishing to take part in MESOMARK testing will be asked to provide one or more samples of blood. The blood samples will then be sent to a national reference laboratory for testing. In conjunction with other clinical and laboratory data obtained by your doctor, decisions regarding your treatment and care may be simplified. You may discontinue testing at any time.

The costs associated with the MESOMARK blood test may not be covered under health insurance, therefore, you may be required to pay all or part of the costs out of pocket. It is recommended that you check with your insurance carrier to determine whether coverage is available under your policy.

SURGERY

Diagnostic Procedures

As previously mentioned in the "Symptoms" section of this website, a diagnosis of mesothelioma from fluid is many times inconclusive. Given this fact, diagnostic surgery becomes a necessary next step in confirming and staging mesothelioma.

Thoracoscopy enables a physician to evaluate the pleural cavity and to conduct multiple tissue biopsies under direct vision. In up to 98% of cases, a definitive diagnosis can be obtained. Often, chemical pleurodesis aimed at relieving the accumulation of fluid in the intrapleural space, can be accomplished during the same procedure. It is also possible to gauge the extent of the tumor, and make a determination of surgical resectability. While less invasive than an open biopsy, it can only be performed on patients where tumor has not obliterated the pleural space.

VATS, or video-assisted thoracic surgery is an alternative to thoracoscopy, although because of its more invasive nature, concerns of tumor seeding increase. By utilizing small incisions, the physician can view the pleural space with the assistance of a camera, and obtain sufficient tissue samples for analysis by a pathologist. Extent of the tumor (i.e., pleural involvement, chest wall invasion) may also determined, and recommendation as to the type of debulking procedure necessary can be made at this time.

Mediastinoscopy is sometimes used as an aid in staging extent of disease when enlarged nodes are seen using imaging techniques.

Laproscopy is used in mesothelioma patients in cases where imaging techniques suggest possible invasion of the tumor through the diaphragm. This information can be important in evaluating a patient for potential pleurectomy or extrapleural pneumonectomy.

Palliative Procedures

Palliative surgical procedures are those which treat a symptom of mesothelioma, without aggressively treating the disease itself.

Chest Tube Drainage and Pleurodesis is considered the most common of palliative treatments. Fluid build-up, or pleural effusion, is most often the first symptom which will prompt mesothelioma patients to seek medical attention. Once this effusion has occurred, it is many times persistent, returning rapidly after initial thoracentesis (draining of the fluid). In order to eliminate this problem, the pleural space must be closed. This is accomplished by use of a talc slurry or other sclerosing agent which produces an adhesion.

Thoracoscopy and Pleurodesis is done in conjunction with VATS using a powdered form of talc versus talc slurry. Both this and chest tube drainage and pleurodesis will be only effective if there is no tumor encasing the lung which restricts its expansion.

Pleuroperitoneal Shunt plays a limited role in palliation for several reasons. It involves placement of a catheter run under the skin from the pleural to the peritoneal cavity. Obstruction of the catheter and possible seeding of the tumor into the abdominal cavity may be concerns.

Pleurectomy, used as a palliative procedure, may be performed where more extensive surgery is not an option. In these cases, it is understood that all visible or gross tumor will not be removed. It is considered the most effective means of controlling pleural effusion in cases where the lung's expansion is restricted by disease.

Potentially Curative Procedures

These procedures are performed with "curative intent". Their goal is removal of all gross disease, with the knowledge that microscopic disease will most likely remain. Adjuvant therapy (another form of treatment in addition to the primary therapy) is typically aimed at eliminating residual disease.

For Pleural Mesothelioma:

* Pleurectomy/Decortication is usually performed on patients with early stage disease (Stage I and selected Stage II), and attempts to remove all gross tumor. If it is found that all tumor can not be removed without removing the lung, this may be done at the same time and is called pneumonectomy.

* Extrapleural Pneumonectomy is considerably more radical than other surgical approaches, and should be carried out by surgeons with great expertise in evaluating patients and performing the procedure itself. (See Finding Specialists.) Because in the past surgery alone has failed to effect a cure, or even to help prolong life for any extended period of time, it is currently being combined with traditional chemotherapy and/or radiation, or other new approaches such as gene therapy, immunotherapy or photodynamic therapy.

General Patient Selection Criteria for Extrapleural Pneumonectomy

Extrapleural pneumonectomy is a serious operation, and doctors experienced in this procedure choose their patients carefully. It is up to each individual surgeon to advise the patient on its feasibility and to conduct whatever tests he/she feel are necessary to optimize the patient's chances for survival and recovery. Following is a general list of patient selection criteria. This list may not be all inclusive, and may vary according to the preference of the surgeon.

o Karnofsky Performance Status score of >70. This score relates to what symptoms of disease the patient may be experiencing and how well they are able to conduct their daily activities. Some surgeons may require a higher performance status than others.

o Adequate renal (kidney) and liver function tests; no significant kidney or liver disease.

o Normal cardiac function per electrocardiogram and echocardiography.

o Adequate pulmonary function to tolerate the surgery.

o Disease limited to the ipsilateral hemithorax (the same side of the chest in which the mesothelioma is located) with no penetration of the diaphragm, extension to the heart or extensive involvement of the chest wall.

o Age of the patient is taken into consideration, but may not be as important as their overall status.

Surgeries of this nature should always be done with a complete understanding of the possible benefits and risks involved. If you are considering surgery as a treatment option, speak openly with your doctor about your concerns, and be sure all of your questions are answered to your satisfaction.

For Peritoneal Mesothelioma:

* Cytoreductive Surgery is aimed at removing all or nearly all of the gross or visible tumor in the peritoneal cavity. In order to treat any remaining cancer cells, Intra-Peritoneal Hyperthermic (heated) Chemotherapy (IPHC) is then delivered to the abdominal cavity. The type of chemotherapy drug used may vary according to the physician’s preference. Click here for more on treatment of peritoneal mesothelioma.

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CHEMOTHERAPY

Chemotherapy is defined as the treatment of cancer using chemical substances. When cancer occurs, abnormal cells continue to divide uncontrolled. Anticancer, or chemotherapy drugs, work to destroy cancer cells by preventing them from multiplying.

Purposes of Chemotherapy

Chemotherapy may be used to achieve different goals, depending on the stage of the cancer at the time of diagnosis and the age and health of the patient. Since chemotherapy for mesothelioma is not considered "curative", the goal is:

* To control the cancer by stopping its spread or slowing its growth.

* To shrink tumors prior to other treatments, such as surgery. This is called neoadjuvant chemotherapy.

* To destroy microscopic disease which may remain after surgery. This is called adjuvant chemotherapy.

* To relieve symptoms, such as pain. This is called palliative chemotherapy, and is given in cases when a drastic reduction in the tumor is not expected.

The most common use for chemotherapy in mesothelioma patients, is as an option for those who are not surgical candidates, however, cancer centers are conducting trials using the neoadjuvant approach (giving chemotherapy before surgery). Alimta (pemetrexed) is a drug approved by the Food and Drug Administration (FDA) for use with Cisplatin in the treatment of patients with malignant pleural mesothelioma whose disease is either unresectable or who are not candidates for curative surgery. Alimta is the first drug approval specific to mesothelioma.

The Alimta/Cisplatin chemotherapy regimen is the first Food and Drug Administration (FDA) approved treatment specifically for malignant pleural mesothelioma. This is currently considered the most effective first-line treatment for mesothelioma patients who are not surgical candidates. A multi-targeted antifolate drug, Alimta works by blocking the enzymes necessary for DNA copying and cell division. During the clinical trial process, Alimta/Cisplatin improved median survival for pleural mesothelioma patients by approximately three months over treatment with Cisplatin as a single agent.

As with any medical treatment, it is important to discuss the use of Alimta with your doctor. This conversation should include all pertinent information regarding effectiveness, administration and possible side effects of the drug combination. It is also important to begin vitamin supplementation of B12 by injection during the week prior to treatment (to be repeated every 9 weeks), and folic acid by mouth daily (to be continued until 21 days after the last cycle of Alimta). Additionally, you will be given an oral steroid medication to minimize the risk of skin rash or other possible side effects. Your doctor will have information on the correct dosages of each medication. Be sure to tell your doctor of any other medications you are taking (including non-prescription drugs) so he may be aware of any adverse interactions.

Alimta/Cisplatin is administered to patients on an outpatient basis every 21 days. This cycle of treatment consists of a 10-minute IV infusion of Alimta followed by a 2-hour infusion of Cisplatin. How many cycles of treatment you receive depends on your response to the drug (regression of the tumor or halt to progression of the disease) and the side effects you might experience.

Side effects of Alimta/Cisplatin are mild to moderate for most mesothelioma patients, i.e., nausea, vomiting and fatigue, and can usually be managed by your doctor. For some patients, however, side effects may be debilitating, and may require a decrease in dosage or removal from the program. All potential side effects should be mentioned to your doctor. Never assume any complaint is minor.

Administration of Chemotherapy

The most common way to administer chemotherapy is intravenously, or through a vein. A thin needle is inserted into a vein in the hand or in the lower arm. Intravenous administration of drugs allows for rapid entry into the blood stream. Drugs may also be delivered via catheters and/or ports.

* Catheters are soft, thin, flexible tubes placed into a large vein in the body. They remain in place for as long as they are needed.

* The catheter may sometimes be attached to a port, a small round plastic or metal disc placed under the skin on the chest. Ports also remain in place for as long as necessary.

Intraperitoneal chemotherapy may also be delivered through a catheter or a port. The catheter is inserted through the abdominal wall. Chemotherapy drugs can then be infused directly into the abdominal cavity for treatment of peritoneal mesothelioma. Ports may also be placed under the skin of the abdominal wall and the catheter tunneled between the skin and muscle into the peritoneum.

Frequently asked questions about being a chemotherapy patient.

Side Effects of Chemotherapy

Cancer cells grow and divide more rapidly than normal cells, but some normal cells also multiply quickly, particularly those in the digestive tract, reproduction system, and hair follicles. It is the damage done to normal cells that causes side effects. The type of side effects you might experience and how severe they are, depend on the type of chemotherapy you are receiving, the dosage given and how your own body reacts. Before beginning any chemotherapy treatment, you will be asked to sign a consent form. Before signing the form, be sure your doctor informs you of all the facts regarding the treatment he/she will be administering, including information about the particular drug or combination of drugs to be used, the possible risks or side effects (including nausea and vomiting and peripheral neuropathy), the number of treatments you will receive and how often, and whether it will be given during a hospital stay or on an outpatient basis. More on vomiting and nausea from chemotherapy. More on peripheral neuropathy. More on anti-nausea treatment for chemotherapy patients.

Click here if you are interested in learning more about chemotherapy for mesothelioma and the types of questions you should ask your doctor.

Chemotherapy Schedules

How often you will receive chemotherapy will be determined by your doctor, taking into consideration factors such as the stage of your cancer, the types of drugs you receive, the anticipated toxicities of the drugs and the time necessary for your body to recover from these toxicities. The doctor may also consider whether the goal of the chemotherapy is to control the growth of the cancer, or to ease symptoms associated with the disease.

In general, chemotherapy treatment is administered in "cycles" — a "cycle" being defined as a period of treatment followed by a period of rest. This cycle allows the cancer cells to be attacked by the drugs, and then allows the body's normal cells time to recover. The combination of drugs used, the length of time to administer the drugs, how often they should be repeated and the number of cycles recommended have been analyzed throughly in clinical trials. For mesothelioma patients, the "standard" treatment is a combination of Alimta and cisplatin, administered IV, with a 10 minute infusion of Alimta followed by two hours of cisplatin, given in 21 day cycles. Modifications to this schedule may be made according to what your doctor feels is appropriate in your particular case.

The number of treatment cycles, or the length of time between the beginning and end of chemotherapy may vary, however in general, 3 to 4 cycles of treatment are given before response is evaluated; 2 to 3 cycles are considered a minimum to assess for effectiveness. After response to the treatment has been determined, the following criteria will be used to decide whether chemotherapy should continue:

* If there is shrinkage of the tumor, or the disease is kept stable, chemotherapy may be continued for as long as it can be tolerated and there is no disease progression.

* If there is continued disease progression, chemotherapy will be stopped, and the patient will be given alternative options.

The goal of setting a chemotherapy schedule is to make treatment as effective, timely and trouble-free as possible, but while the drugs are working to kill cancer cells, they may also affect healthy cells causing side effects. One of the most common side effects, and one your doctor will monitor carefully, is a chemotherapy-induced low white blood cell count (neutropenia) which means your immune system is weakened, therefore leaving you more prone to infection. While this side effect is anticipated when someone is undergoing chemotherapy, it can cause delays in your treatment schedule, or changes in the dosage of the drugs you will receive. Click here for more on understanding your blood counts.

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Note to Patients:

Chemotherapy treatment should be a cooperative effort between you and your doctor. The interaction that takes place is important to your health. It will not only help you feel better, but will also address any potential problems with miscommunication.

1. It is necessary for your doctor to be aware of any side effects which may result from your chemotherapy treatment.

These may include:

* Fever of, or greater than 101 degrees

* Nausea or vomiting

* Diarrhea or constipation

* Fatigue

* Tingling or numbness in the fingers or toes

* Ringing in the ears

* Bruises or rashes

* Sores in the mouth or throat

2. Taking other medication of any kind can alter the effects of chemotherapy or cause undesirable interactions.

Be sure you report all over-the-counter and prescribed medicines to your doctor. Don’t take aspirin unless it has been approved by your doctor. Ask your pharmacist if aspirin is contained in any drugs you plan to purchase.

3. Take extra care with your daily health.

Try to maintain a stable weight by eating a healthy diet and drinking plenty of fluids. If your stomach is upset, ask your doctor for helpful hints or work with a nutritionist who can tailor a program to your needs. Brush your teeth after every meal, or if you can’t brush, rinse your mouth thoroughly with water.

Stay away from people who have colds or the flu. Chemotherapy can compromise your immune system and lower your resistance to germs. Make sure you keep appointments for blood work – these tests help your doctor monitor your health.

4. Be open about your feelings regarding your treatment.

It is normal to feel sad, angry or afraid, however, letting these emotions get out of control can be detrimental to your overall well-being. Seek out the help of family, friends, your doctor, a counselor or a support group.

RADIATION THERAPY

Radiation therapy, also called radiotherapy, treats cancer by using penetrating beams of high energy or streams of particles called radiation. In treating mesothelioma, radiation may be used aggressively in combination with surgery, or palliatively to control symptoms.

In an aggressive combined modality approach, radiation is used to attack microscopic or residual disease remaining in the chest cavity after extrapleural pnuemonectomy. An example of this is Intensity Modulated Radiation Therapy (IMRT), which uses x-rays of varying intensities in conjunction with computer generated images to deliver targeted radiation directly to cancer cells while reducing the amount of radiation to surrounding healthy tissue. More on Intensity Modulated Radiation Therapy (IMRT).

Used palliatively, radiation can help control metastases (spread) of the tumor along tracks left by invasive procedures such as thoracoscopy, needle biopsy and chest tube drainage, or to control disease symptoms, such as pain or shortness of breath.

An exciting new development in radiation oncology is tomotherapy. A brief description of steps in the helical tomotherapy process.

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