Chemotherapy

How chemotherapy is used to treat mesothelioma

Chemotherapy does not offer a cure for mesothelioma, but it is often used in treatment of the disease.  Chemotherapy works by using powerful chemicals to kill cancer cells.  Systemic chemotherapy may be helpful to shrink or slow the growth of a tumor in the chest that can’t be removed surgically.  Chemotherapy may also be used prior to surgery to make the operation easier to perform; this is called neoadjuvant chemotherapy.  When chemotherapy is used following surgery to minimize the risk that the cancer will reappear, it is called adjuvant chemotherapy.  Chemotherapy that is performed to reduce pain is a palliative treatment.

Chemotherapy drugs are customarily given by injection into a vein. This depends on the type of the cancer, its location, and the specific drug used.  Chemotherapy may also be delivered by mouth or into the muscle or skin.  Sometimes, chemotherapy drugs are heated and placed directly into the part of the body where the mesothelioma is found.  The general practice is known as intracavitary chemotherapy.  With pleural mesothelioma, the drugs are inserted into the chest cavity (called intrapleural chemotherapy); the chemicals are placed in the abdominal cavity in the case of peritoneal mesothelioma (called intraperitoneal chemotherapy).  Using this method of administration, chemotherapy drugs are able to penetrate the mesothelioma directly without harm to healthy cells in other parts of the body.  Doctors are thus able to administer higher doses of chemotherapy drugs.

Although it may work well for fighting other types of cancer, single agent chemotherapy is not generally effective for treating mesothelioma.  The use of two or more chemical agents in combination chemotherapy holds more promise.

Chemotherapy is typically delivered in cycles, with each segment of treatment followed by a period of rest to give the body time to recover.  A chemotherapy cycle customarily lasts from three to four weeks.  Doctors seldom prescribe chemotherapy for patients in poor health, though advanced age alone would not prevent a patient from receiving chemotherapy.

Patients who receive chemotherapy drugs usually become fatigued.  Nausea, vomiting and hair loss are also frequent complaints.  The side effects experienced will vary according to the drug, as well as how much is given and for how long.  There are a number of chemotherapy–related drugs and therapies that may be prescribed to help reduce the side effects that often follow chemotherapy.

Single Agent Chemotherapy

A regimen of single agent chemotherapy consists of treatment with a single drug.  The problem is that most single agent chemotherapy drugs have not proven to be effective in mesothelioma treatment.  Most have a response rate of less than twenty percent and have high toxicity levels.

The chemotherapy drug Alimta® (pemetrexed) has probably been the most successful single agent chemotherapy drug evaluated thus far.  In a phase II clinical trial conducted in the United States, Italy and Germany, the reported response rate for patients receiving Alimta® was sixteen percent.  Still, Alimta® shows even more promise when used in combination chemotherapy with cisplatin.

Although the following drugs have not been shown to affect overall survival, they do appear to be active against mesothelioma:

  • 5–Fluorouracil
  • Alimta®
  • Carbonplatin (Paraplatin) (though serious side effects have been reported)
  • Cyclophosphamide
  • Doxorubicin
  • Epirubicin
  • Ifosfamide
  • Interferon
  • Methotrexate (high dose)
  • Mitomycin C
  • Navelbine (Vinorelbine)
  • Onconase (Ranpirnase)
  • Platinol® (Cisplatin)
  • Timetrexate

When a regimen of single agent chemotherapy is prescribed, the accepted “standard” for treating mesothelioma has been cisplatin.  It has also been reported that vinorelbine alone may provide relief for mesothelioma symptoms without high toxicity levels.  The recent focus among scientists who treat mesothelioma with chemotherapy, however, has been to explore chemotherapy drug combinations that seem to offer more promise than traditional single agent regimens.

Combination Chemotherapy

Combination chemotherapy can be more useful in treating mesothelioma than single agent chemotherapy because the drugs in combination work on different systems or affect the same system in different ways. The combined drugs complement one another to capitalize on their power to destroy cancer cells.

The most–studied combination chemotherapy used to treat mesothelioma is the combination of Alimta® and Platinol® (cisplatin).  Physicians have reported that patients receiving Alimta® in combination with cisplatin demonstrated measurable improvement in their mesothelioma symptoms, including reduced shortness of breath and less pain.  Clinical trials suggest that patients who use this regimen may live up to 30% longer.  Where surgery is not possible, Alimta® is giving hope to mesothelioma patients. 

Several other combination chemotherapy regimens have been shown in small phase II clinical trials to provide higher response rates in mesothelioma patients than do single agent chemotherapy drugs.  The combination of raltitrexed and oxaliplatin has demonstrated encouraging response rates.  In addition, the combination chemotherapy regimen consisting of gemcitabine with cisplatin and vinorelbine appears to offer mesothelioma patients an improved quality of life.  Doctors are also evaluating the combination of Gemzar® and Alimta® in clinical trials.  Finally, scientists are conducting research on second line chemotherapy treatments for patients who do not respond to chemotherapy the first time.

Intracavitary Chemotherapy

One of the more recent developments in the treatment of mesothelioma involves intracavitary chemotherapy.  This type of chemotherapy has been used in combination with surgery and radiation (called multimodality therapy) to offer promise in improving the survival rate in some patients whose diagnosis came at an early stage of the disease.

Intracavitary chemotherapy was designed in particular to combat the problem that occurs when a tumor that was surgically removed reappears in the same area in which it originated or appears for the first time in the abdomen. The treatment has been studied extensively in cancers of both the chest and the abdomen.  By administering cisplatin, a chemotherapy drug, directly into the chest and/or abdominal cavity, doctors are able to deliver a much higher dose than would be possible for traditional chemotherapy administered intravenously through the bloodstream.  With the intracavitary approach, the chemotherapy drug can enter the tumor cells directly by diffusion without causing a toxic reaction in the body’s healthy cells.  In addition, scientists have discovered that the ability of the chemotherapy to kill off cancer cells is increased when it is heated. 

Intracavitary, heated chemotherapy is generally performed during the surgery in which the tumor is removed.  With the patient still under anesthesia in the operating room, chemotherapy is administered into the chest and/or abdominal cavities.  Any surfaces on which tumor cells may remain are contacted directly with the chemotherapy drug.  At the same time, a ‘cytoprotective’ agent is given intravenously to protect healthy cells near the site of the surgery and chemotherapy treatment. 

Phase I studies of this treatment demonstrated that patients can safely be treated with chemotherapy drugs in this way.  These early studies were not meant to evaluate whether the treatment was effective, though the results have been encouraging for patient survival and the time span to any relapse.  Phase II studies have been completed, but not yet released. 

Chemotherapy–Related Drugs

Taxotere and Taxol

Taxotere and Taxol are drugs that help to kill cancer cells when cancer reappears after a previous chemotherapy regimen.  These drugs, which are delivered through intravenous infusion, inhibit the reproduction or duplication of cancerous cells.

Endostatin

Endostatin is a promising natural protein that has been demonstrated to inhibit the growth of blood vessels.  By administering Endostatin, doctors can actually “starve” a cancerous tumor due to the lack of blood.  Endostatin is still being tested in clinical trials, however, and has not been approved for general use.

Anti–Nausea Drugs for Chemotherapy Patients

Nausea is one of the most common side effects of chemotherapy.  Zofran is one medication that is often effective in treating nausea.  Recent research has suggested that Zofran may be even more effective when used in combination with Rezonic, a new drug that has not yet been approved by the U.S. Food and Drug Administration for treating nausea.  Other anti–nausea medications include Emeset and Oncoden.  The drugs help to control nausea from all causes, including chemotherapy, radiation, and post–operative nausea. 

 

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