A mesothelioma diagnosis can be devastating. However, while there is no cure for mesothelioma – that is, no way to permanently eliminate the disease – you can undergo treatments that can help slow the progress of the disease and ease the severity of your symptoms.

Even though there is no cure, with mesothelioma, as with most serious diseases, treatment strategies are referred to as either curative or palliative in intent. Curative treatments attempt to cure or control the disease, while palliative treatments are aimed at reducing symptoms and making the patient more comfortable. The earlier mesothelioma is detected and diagnosed, the more successful curative strategies tend to be. However, it’s not uncommon to begin your treatment with curative strategies and move to palliative treatments later on.

The treatment plan you and your doctor develop depends on several factors, including the type and stage of disease and your overall health. Conventional mesothelioma treatment plans generally include chemotherapy, radiation and surgery – or, most commonly, a combination of these methods (called multimodal treatment). Less conventional treatments include experimental options such as gene therapy. Alternative medicine offers some unique benefits to improve your general sense of well-being and even counteract some of the side effects of conventional treatments; learn more about these options in Chapter 5.

This chapter walks you through your conventional treatment options, showing you the pros and cons and what you can expect from each. And, because choosing the right doctor and treatment facility is critical to the success of your treatment plan, the final section of this chapter is devoted to this topic.

Surgery

Surgery may be used to diagnose mesothelioma and determine the stage or to extend your life by removing tumors that are causing pain or other symptoms (called palliative surgery). Unless mesothelioma is diagnosed in its early stages, surgery may not be an option.

Diagnostic surgery

Your thorax is the upper part of your torso. The thoracic cavity is the area of your torso from your neck to your diaphragm (see Chapter 1) that contains your heart and lungs. Thus, any surgery involving your thoracic cavity is called thoracic surgery.

Surgeons use one of two main techniques for thoracic surgery:

• Thoracotomy. In a thoracotomy, the surgeon makes a large incision in the chest wall to gain access to the heart, lungs, and diaphragm. Where the incision is made depends on the type of surgery being performed. For most mesothelioma patients, the incision will be along the ribcage on the side of the affected lung.
• Video-assisted thoracic surgery (VATS). In VATS, the surgeon makes a small incision and uses a tiny camera connected to a monitor to view the interior of the thoracic cavity. VATS is less invasive because it causes less damage to the muscle surrounding the chest cavity. However, some surgeries require the larger incision of a thoracotomy to remove damaged tissues and organs.

Life-Extending Surgery

The goal of curative surgery is to remove all visible traces of disease – called a macroscopically complete resection. Resection is the surgical removal of all or part of an organ, specific tissue or structure. Macroscopic means visible to the naked eye.

If you are a candidate for curative surgery, you’ll undergo one of two procedures: pluerectomy/decortication or extraplueral pneumonectomy. Both of these surgeries are considered radical because they’re highly invasive and involve significant recovery time. However, they are known to extend the life of patients with early-stage mesothelioma.

We strongly believe that these surgeries should be performed by recommended surgeons at mesothelioma treatment centers (see Appendix A).

The following sections describe these procedures in more detail.

Pleurectomy/Decortication

Pleurectomy means removing the pleura. Decortication means removing the layer of fibrous tissue surrounding the lung; when this tissue is damaged, it can restrict the lung’s ability to expand when you inhale.

A pleurectomy/decortication (or PD) surgery involves cutting through the chest wall on the side of the affected lung and pleura and spreading the ribs apart (occasionally the surgeon will remove one rib to gain better access to the chest cavity), then removing the pleura and peeling away the fibrous layer around the lung. In some cases, the surgeon also will remove the pericardium (see Chapter 1) and the diaphragm, and will likely take lymph nodes from the chest cavity so they can be tested for signs of cancer and to help identify the stage of the disease. The results of the lymph node tests will be used to guide the rest of your treatment plan.

If the surgeon removes the diaphragm or pericardium, he or she will replace it with a mesh material designed to imitate the function of the original tissue. Several drainage tubes will be inserted to prevent fluid build-up. After surgery, the patient typically spends a few days in the intensive care unit to ensure there are no complications, then embarks on a rehabilitation program to restore muscle movement and lung function.

Pleurectomy/decortication is a highly invasive procedure and requires a lengthy recovery period. Even without complications, you should expect that it will be some time before you feel completely recovered from the operation.

The most common complications with this procedure involve blood loss, problems with reconstructing the diaphragm and pericardium, and breathing problems associated with manipulating the lung during the surgery. However, surgeons know what to watch for and how to deal with these complications, and most feel that the operation is worth it for patients with early-stage mesothelioma because it maximizes your odds of long-term survival.

Extrapleural Pneumonectomy

An extrapleural pneumonectomy (or EPP) is similar to the pleurectomy/decortication procedure described above, but in an EPP, the surgeon also removes the affected lung – and possibly the diaphragm. EPPs are done when the mesothelioma has spread beyond the pleura and has begun infiltrating the lung, or when asbestos-related lung cancer is present in addition to mesothelioma.

In many cases, a surgeon goes into the procedure expecting to perform a pleurectomy but finds that the imaging tests (see Chapter 3) didn’t accurately reveal the extent of the disease. (The opposite also can happen but is more rare.) In these cases, an EPP may be performed.

Because mesothelioma is most often diagnosed after it has spread, EPP was a fairly common procedure. However, recent studies have shown that pleurectomies are as effective as EPPs in extending patients’ lives. Pleurectomies also have the advantage of saving your lung.

Complications can be more severe than with a pleurectomy, but experienced surgeons are aware of the potential complications and can make adjustments as needed.

Although not every patient is a good candidate for EPP, those who are – and who undergo other forms of treatment in combination with the surgery – tend to have longer survival times than those who opt not to have the surgery.
Tip: Dr. Harvey Pass at New York University is a leading surgeon for mesothelioma patients. See his entry in Appendix A (page 109).

Palliative Surgeries

Not all surgeries are intended to treat the disease itself. Some are intended to relieve symptoms and improve the patient’s quality of life. Palliative surgeries for mesothelioma reduce fluid build-up or pressure that makes it difficult to breathe. They don’t affect the progress of the disease itself, but – combined with other treatments – they can lessen your symptoms and make you feel better.

The most common palliative surgeries for mesothelioma are:

• Debulking pleurectomy. In a debulking pleurectomy, the surgeon removes as much of the cancer from the pleura as possible to ease the pressure on the lungs. This procedure is often combined with pleurodesis (see the next bullet) to make breathing easier and improve the patient’s quality of life.
• Pleurodesis. In this procedure, the surgeon fuses the pleura lining the lungs with the parietal pleura surrounding the chest wall and diaphragm. Fusing these pleura together prevents fluid build-up and pleural effusions (see Chapter 1). Pleurodesis is the most common palliative surgery for mesothelioma patients.

Consider all your options before you decide to have a pleurodesis performed. This procedure may make it impossible for you to have a pleurectomy later on should you need it.

• Decortication. Decortication is a procedure in which the surgeon strips away the layer of fibrous tissue surrounding the lung. When this fibrous tissue is damaged, it loses its elasticity and keeps the lung from inflating fully when you inhale. Removing this layer allows the lung to expand better. Decortication sometimes is performed along with pleurodesis to ease symptoms.
• Catheters and shunts. Patients who have late-stage mesothelioma and don’t want to undergo more invasive treatments sometimes choose to have catheters or shunts implanted to relieve the symptoms of fluid build-up in the pleura surrounding the lungs or abdomen.

Palliative surgeries are designed to help relieve symptoms and make you more comfortable. They don’t cure your disease or stop or slow down the progress of mesothelioma.

Chemotherapy

Chemotherapy is the most common treatment for mesothelioma because, most of the time, the disease is already in its later stages (see Chapter 1) by the time it’s diagnosed. Chemotherapy is the use of chemicals to destroy cancerous cells. Normal cells have complex regulatory structures that control how quickly they grow and how often they divide. When they grow or divide too fast, these regulatory mechanisms force cells to commit suicide, a process called apoptosis. In cancer cells, the normal regulatory mechanisms break down, so these cells grow and divide uncontrollably. Chemotherapy drugs are designed to interfere with the process that drives this out-of-control growth.

Unfortunately, chemotherapy drugs don’t distinguish between cancerous and normal cells, so they kill off healthy cells as well. Most chemo drugs target rapidly dividing cells, because this is a hallmark of cancerous cells. But some normal cells in your body divide rapidly, too – particularly cells in your bone marrow that generate new red blood cells, the cells that line your stomach and intestines, and the cells in your hair follicles that generate new hair growth. Because most chemo drugs can’t differentiate between healthy fast-dividing cells and cancerous cells, patients who undergo chemotherapy commonly experience anemia, nausea or other digestive disruption, and hair loss.

Some of these side effects can be controlled with medication, and researchers are working on identifying specific portals in cancer cells (which aren’t present in healthy cells) that would allow the chemicals to penetrate and kill off cancer cells without affecting normal cells. At present, though, chemotherapy is still an imperfect treatment.

The most common chemo treatment for mesothelioma is the combination of Alimta (pemetrexed), which was approved by the U.S. Food & Drug Administration in 2004, and cisplatin, a long- standing staple of many chemo treatments. More information about each of these drugs is in the following sections, which provide details on different types of chemo drugs, when chemotherapy is used, and how it’s used.

Types of Chemotherapy Drugs

In general, chemotherapy drugs are divided into four types or classes, depending on the mechanism they use to kill off cancer cells:

• Antifolates. Folic acid, or folate, is a crucial component of cell growth and division; the DNA in cells needs folic acid to replicate itself and generate a new cell. Antifolate drugs inhibit cell growth and division by interfering with DNA replication. Antifolates are part of a larger class of drugs known as antimetabolites, which work by fooling cells into thinking they’re the substances the cells need to grow and divide. But these drugs have important differences that inhibit rather than encourage cell metabolism, the chemical processes cells use to function and reproduce. In the case of antifolates, for example, cells take in the drug and attempt to use it help to replicate DNA, but because the drug isn’t really folic acid, the replication process breaks down.
  Antifolates are believed to work with mesothelioma because this particular type of cancer cell has a high number of receptors that are tuned to taking in folic acid. Because of the higher number of these receptors, mesothelioma cells are more susceptible to being “fooled” into taking in antifolate drugs instead of actual folic acid.

  Pemetrexed (also known as Alimta) is an antifolate drug commonly used in mesothelioma chemo treatments. This drug slows the growth and spread of cancer cells and is effective at decreasing pain and extending the lifespan of cancer patients. About 80 percent of mesothelioma patients who undergo chemotherapy take pemetrexed with cisplatin (see the next section). This combination has shown good results in extending mesothelioma patients’ lives.

• Platinum agents. Platinum agents attack a cell’s DNA and disrupt its structure, thus triggering the cell’s pre-programmed “suicide” response (apoptosis). Cisplatin is the oldest of the chemo platinum agents and is still considered the standard (in combination with pemetrexed) for mesothelioma chemotherapy. Other platinum agents include carboplatin and oxaliplatin. If a patient has trouble tolerating cisplatin, which has significant side effects in some patients, carboplatin may be used as a substitute in mesothelioma treatment.
• Anthracyclines. Anthracyclines damage a cell’s DNA and thus interfere with all stages of a cell’s life cycle. They’re commonly used to treat a variety of cancers, particularly leukemia, because they’re quite effective in killing cancer cells before they reproduce. Unfortunately, mesothelioma cancer hasn’t responded well to anthracyclines in studies, so this class of chemo drug isn’t normally used for mesothelioma.
• Vinca alkaloids. Vinca alkaloids target the process of cell division, called mitosis. These drugs interfere with the tiny structures that help move parts of DNA during cell division, thus preventing a cell from reproducing itself. Although few vinca alkaloids have proven to be effective in treating mesothelioma, researchers are investigating one of the newer agents, vinorelbine, which has shown promise in targeting mesothelioma cells. However, vinorelbine also presents some serious side- effect risks in many patients, so this agent hasn’t yet moved into the standard treatment for mesothelioma.

The current standard chemotherapy for mesothelioma combines cisplatin and pemetrexed, which has proven to be the most effective treatment so far. The combination of agents attacks mesothelioma cells from two angles – pemetrexed interferes with cell metabolism, and cisplatin triggers a cell’s “suicide” response. In addition, studies have indicated that most patients tolerate the toxic effects of cisplatin better when it’s combined with pemetrexed.

Researchers are investigating other types of anticancer agents that use other mechanisms to defeat cancer. Many of these agents are being tested in clinical trials (see the Experimental Treatments section later in this chapter for more information on what clinical trials are and how they work) and are not yet considered standard treatments for mesothelioma.

When Chemotherapy is Used

One of the most insidious traits of cancer cells is that they can detach themselves from the original site of the cancer, travel through your body and hide for months, even years, surviving without a blood supply until enough of them land in the same place to form a new tumor. Surgical techniques often can remove visibly diseased tissues and organs, but they can’t guarantee that all of the cancer cells are gone. This is why many cancer patients – including mesothelioma patients – undergo both surgery and chemotherapy or radiation therapy (see the Radiation section later in this chapter). Chemo and radiation target cancer cells that surgery misses – what doctors call occult disease.

Chemo can be used before surgery to shrink a tumor, or after surgery to destroy cancer cells the surgery doesn’t remove. When you undergo chemo before surgery, your doctor may use the term neoadjuvant chemotherapy. Chemo following surgery is called adjuvant chemotherapy. It’s unclear whether chemo before surgery has any significant benefits for mesothelioma patients because this disease, unlike many other forms of cancer, tends to be diffuse, or spread out over a large area.

Most people think of chemo as a curative treatment; that is, chemo is often intended to kill all or most cancer cells in your body and send the cancer into remission. But chemo also may used as a palliative therapy – not intended to cure, but to manage the symptoms of your disease. (Given the side effects, however, some patients choose not to undergo chemo for palliative purposes.)

How Chemotherapy is Used

When your doctor discusses chemotherapy with you, he or she will likely use three terms to describe the treatment: regimen, cycle, and course. To the layperson, these terms seem interchangeable, but they have specific meanings when you’re talking about chemo:

• A chemotherapy regimen describes the overall treatment plan. Your regimen will identify the chemo agent(s) the doctor will use; any secondary treatments, such as vitamin supplements to help your body better tolerate the effects of the chemo (for mesothelioma, folic acid and vitamin B12 are usually prescribed for this purpose); and the number and schedule of your treatments. The regimen is the complete roadmap of your chemo treatment.
• Chemotherapy regimens are considered either first-line or second-line First-line therapies are the standard treatments for a particular disease – for mesothelioma, first-line chemotherapy is the combination of cisplatin and pemetrexed
  (see “Types of chemo drugs” earlier in this chapter).
  However, some patients don’t respond well to first-line therapies; those patients typically receive second-line therapies. Unfortunately, there is no standard second-line chemotherapy for mesothelioma, but researchers are investigating several drugs that could become a second-line standard for this disease.
• A chemotherapy cycle is one leg of the journey on your chemo roadmap, consisting of one treatment and one resting period before the next treatment. The resting period gives your body time to recover from the side effects of the chemo. In addition, because chemo drugs target dividing cells and cells divide at different times, multiple cycles of chemo are more effective at killing off cancer cells than a single treatment would be.

  Delivering chemo on this treatment-and-rest cycle also helps the doctor determine how well your body tolerates the drugs being used and make adjustments to either the drugs or the dosage if needed.

• A chemotherapy course is the whole journey plotted out on your regimen. When you’ve completed all the treatment-and-rest cycles prescribed in the roadmap, you’re done with your chemotherapy course. If the cancer reappears later, your doctor may recommend another course of chemotherapy.

Unless you’re already hospitalized, you’ll receive your chemo treatments on an outpatient basis. Sometimes chemo drugs are given in pill form or in a direct injection, but most commonly they’re administered slowly through an IV drip. Your doctor may insert a port, usually in the chest, that will stay in throughout your chemotherapy course; when you come in for a treatment, the drugs will be administered through the port. After you’ve received the treatment, you’ll return home (although you probably will want to have someone drive you to and from your treatment in case you experience nausea or other side effects from the drugs).

Researchers are looking into another delivery method called isolated perfusion chemotherapy, or IPC. Instead of circulating throughout your bloodstream, the chemo drugs are delivered into a particular area of the body, which tends to reduce side effects. This method also allows for the drugs to be heated, which improves their absorption by malignant cells and tissues. For mesothelioma patients, IPC is being studied in both the pleural surfaces (intrapleural perfusion chemotherapy) and in the abdomen (intraperitoneal perfusion therapy).

Radiation Therapy

Radiation therapy uses high-energy ionizing radiation to kill cancer cells. Ionizing radiation changes the structure of DNA in cells, thus inhibiting growth and division. Like chemotherapy, though, radiation therapy doesn’t differentiate between healthy and cancerous cells, so the treatment damages normal cells as well. The side effects of radiation are similar to those for chemotherapy and include hair loss, digestive problems, and anemia.

Advances in radiation technology show promise in using this therapy to treat mesothelioma, although researchers are pushing for more studies to ensure that these new technologies are safe as well as effective. External-beam radiation therapy uses a machine to deliver targeted blasts of radiation to specific parts of the body. Combined with CT and MRI technology (see Chapter 3), radiation beams can be directed to target malignant tissues, thus minimizing the damage to healthy cells and tissues. This is important because your heart and lungs are highly sensitive to radiation, and the targeting ability affords some protection against unintended damage to these organs.

Most commonly, radiation therapy for mesothelioma involves targeted doses of radiation following surgery in locations where cancer cells are considered most likely to spread, such as around incision sites. At present, because of the risk of damaging critical organs and tissues, most doctors don’t use radiation as a primary therapy for treating mesothelioma, but it has been proven useful and effective in combination with surgery.

New Therapies

Although chemotherapy, radiation and surgery remain the most common and conventional treatments for mesothelioma, researchers are investigating other treatments for this and other types of cancer. These experimental treatments include:

• Gene therapy. Gene therapy aims to target tumors without harming healthy cells by inserting a “suicide” gene directly into a tumor. This gene makes cancerous cells sensitive to drugs that normally aren’t effective against cancer, and the drug affects only cancer cells. Gene therapy is in clinical trials to determine both its safety and effectiveness for large- scale use as a cancer treatment.

Tip: Dr. Daniel Sterman at the University of Pennsylvania is a lead investigator using gene therapy in mesothelioma; see his entry in Appendix A (page 112).

• Photodynamic therapy. Photodynamic therapy has shown promise in treating other forms of cancer and is now in the experimental stage for treating mesothelioma. The patient takes a drug called a photosensitizer that makes cells sensitive to light at specific wavelengths; the drug collects in cancerous cells but not in healthy cells. After the cancer cells are sensitized, a surgeon inserts fiber optic cables into the patient’s body (typically through open-chest surgery) and beams the specific wavelength of light at the cancer cells. In response to the light, the drug produces a toxic oxygen molecule that kills the cancer cell.

Tip: Dr. Joseph Friedberg is using photodynamic therapy at the University of Pennsylvania; see his entryin Appendix A (page 111).

• Immunotherapy. Immunotherapy (also called biological therapy or BRM, for biological response modifiers) aims to boost the body’s immune system response to effectively isolate and kill cancerous cells. Like the other new therapies listed here, immunotherapy is being tested in clinical trials to determine its safety and effectiveness.

Clinical Trials

Clinical trials test the safety and effectiveness of drugs, medical devices, and surgical procedures in humans. These controlled tests typically have three or four phases. In Phase I trials, the focus is on safety, not effectiveness; researchers select a few dozen people (sometimes even fewer) to evaluate any side effects. If the drug, medical device or surgical procedure appears to be safe after Phase I, testing moves to Phase II, which involves several hundred people and lasts one to three years. Phase II trials measure both safety and effectiveness. Phase III trials are long-term studies – often eight to 10 years – to evaluate long-term safety and effectiveness; they typically involve between 1,000 and 3,000 patients and are implemented as part of the patients’ regular medical care. Phase IV studies are carried out after the treatment has received federal approval and is available to anyone who needs it. The goal of Phase IV monitoring is to identify any potential problems with the treatment as well as other possible uses. For example, Phase IV monitoring led to the discovery that the antidepressant Wellbutrin is sometimes useful as a stop-smoking aid.

There are benefits and risks to participating in clinical trials. In all trials, patients are randomly selected to receive either the treatment being tested or a dummy treatment (called a placebo) that’s harmless but also doesn’t provide any benefit. In single-blind trials, the physician administering the treatment knows which patients are getting the real treatment and which are getting a placebo, but the patients don’t know which treatment they’re getting. In double-blind trials (which are considered more reliable), neither the patient nor the physician knows who’s getting the real treatment and who’s getting the placebo.

Clinicaltrials.gov has a searchable database of clinical trials around the world. You can use the database to get up-to-date information on the latest clinical trials for mesothelioma treatments, including trial locations, the kind of patients the trial’s administrators are looking for, and what to expect if you apply for and are accepted for the trial. As always, be sure to talk with your doctor about your specific situation and the pros and cons of participating in such trials.

Finding a Doctor and Treatment Center

Although your primary care doctor may perform the initial evaluation and order tests, he or she should refer you to a mesothelioma specialist who will lead the medical team in confirming the diagnosis and formulating a treatment plan. Remember, mesothelioma is a rare form of cancer, and you’ll get the best care from a doctor (and a facility) that specializes in this disease. Often, patients meet with two or more mesothelioma specialists to fully understand their options. Appendix A list mesothelioma treatment specialists, and recommended doctors and facilities are marked with an asterisk.

When you meet with a mesothelioma specialist (or any doctor, for that matter), it’s a good idea to write down any questions you may have so you don’t forget to ask while you’re with the doctor. You also may want to have someone go with you to your appointments to help ensure you get the answers you need and understand any instructions or warning signs the doctor wants you to be aware of.

Here are some common questions mesothelioma patients want answered when they visit their doctor:

• What kind of mesothelioma do I have?
• What part of my body is affected?
• What stage is my mesothelioma?
• How do we know whether it has spread?
• What are my treatment options?
• What are the pros and cons of my treatment options?
• What are my chances of beating this?
• What should I expect during treatment?
• Is there anything else I can do to improve my chances or my quality of life?

You also may want to ask about the experience your doctor and treatment facility have with cases like yours. Don’t be afraid to ask how many patients the doctor or hospital has treated or what their general experience has been with cases like yours.

It’s important to see a mesothelioma specialist. These doctors will be most familiar with the disease and treatment options that can extend your life and improve the quality of your life.

Your comfort level is just as important as their expertise. When you’re considering doctors and treatment facilities, keep the following things in mind:

• Do you feel comfortable with the doctor and staff?
• Do the doctor and staff take the time to answer your questions and make sure you understand what they’re telling you?
• Do the doctor and staff seem comfortable with answering your questions?
• Do you feel that the doctor and staff respect you as an individual?
• Does the doctor ask you how you feel about different treatment options?
• What will your care after surgery be like?

Several resources are available to help you locate appropriate doctors and treatment facilities. Some magazines, such as U.S. News &World Report, rank treatment centers according to their areas of expertise.

We’ve listed several doctors and treatment centers that specialize in mesothelioma in Appendix A of this book. You also can find doctors and treatment centers near you by visiting www.mesotheliomahelp.net.