Mesothelioma Treatment - Cancer Chemotherapy Drugs

Mesothelioma treatment varies with the stage of the disease. Some cancer treatments can work well in the first stage of the disease, such as a combinations of certain chemotherapy drugs but will not be as effective if the mesothelioma cancer has advance past the area where it started.

Mesothelioma Treatment options for localized (Stage 1):

Mesothelioma treatment with Surgery:

If the disease is still fairly limited, it may be an option to remove the pleural membrane alone, taking the tumor with it. This is called pleurectomy or decortication.

If the disease has become more widespread in the area, and it isn’t possible to remove individual tumors, there is a second method called extrapleural pneumonectomy. It is an attempt to remove all malignancy by removing both the inside and outside layers of the pleura, the pericardium and half of the diaphragm on the same side, and part or all of the lung. There are serious complications in 25% of the the patients who have this procedure. The best way to predict the outcome is to look at the type of cancer cell present (the prognosis is better with epitheloid-type) and how well the lungs are functioning before surgery, but there isn’t any research that shows a significantly better survival rate after the procedure. While the patient might live longer before the disease recurs, it is not clear that the overall survival time is any longer. Other types of treatment (like chemotherapy or radiation) may also be used to control any residual malignancy.

When cancer first recurs after an extrapleural pneumonectomy, it is more often in the form of distant metastasis rather than a recurrence of the localized tumor.

Mesothelioma treatment with Radiation:

Unfortunately, malignant mesothelioma doesn’t respond well to radiation therapy alone, and because of the location of the cancer, treatment is over a wide area (like one whole side of the chest area) so toxicity is higher. High-dose external-beam radiation can prolong survival, and it may also help with symptoms like pain and the collection of fluid. It is also used in conjunction with surgery to destroy microscopic bits of malignant tissue left behind.

One method of delivering radiation therapy, Intensity Modulated Radiation Therapy (IMRT), using computer-generated images in conjunction with various intensities of x-rays to target the cancerous cells more precisely and limit the toxicity of the treatment.

Another method, implanting radioactive isotopes close to the site of the malignancy, can also increase the dose of radiation delivered to the tumor, with less toxicity to healthy tissue.

Mesothelioma treatment with Chemotherapy:

Mesothelioma treatment with chemotherapy is not considered curative by itself, but it can be used for several different reasons Stage 1 mesothelioma treatment:

To control the cancer by limiting its spread or slowing its growth
To shrink tumors before using another form of treatment, for example, surgery. (This is neoadjuvant chemotherapy)
To destroy any microscopic cancer cells left behind after surgery. (This is adjuvant chemotherapy.)

There are two ways of delivering chemotherapy: either systemically (by taking pills or by injection), or directly into the pleural space. Recently, combinations of chemotherapy drugs have appeared to be more effective than any of them used alone; for example, Alimta used in conjunction with cisplatin appears to be more effective than cisplatin alone.

Intrapleural chemotherapy works best in Stage 1 mesothelioma treatment, because it affects only the primary site of the malignancy. As the tumor grows, this method becomes less effective, because the tumor fills up more of the space between the pleural membranes, and the chemotherapy solution used doesn’t penetrate very far into the tumor. The more quickly this treatment is used in the course of the disease, the more likely it is to help.

Chemotherapy agents used in malignant mesothelioma treatment:

Adriamycin (Doxorubicin) – This agent has been used for a number of years against a range of cancers.
Aroplatin (L-NDDP) – less toxic than more traditional chemotherapy drugs
Carboplatin – This chemotherapy agent is used primarily for ovarian and lung cancer.
Cisplatin – A platinum-containing chemotherapy agent that is used to treat various forms of cancer, including metastatic disease. It is frequently combined with newer drugs to increase effectiveness.
Cyclophosphamide (Endoxana®) – A chemotherapy treatment used in various forms of cancer.
Edatrexate – Another drug which is more effective used in combination with cisplatin.
Endostatin – Reduces the growth of blood vessels, to starve the tumor.
Gemcitabine – Inhibits the growth of cancer cells, which are eventually destroyed.
Methotrexate – This agent works by limiting cell growth. It is used for treatment of other diseases as well as cancer.
Mitomycin – One of the older chemotherapy drugs, used on many forms of cancer.
Vinorelbine (Navelbine®) – single agent or in combination with cisplatin for the first-line treatment of ambulatory patients with unresectable, advanced non-small cell lung cancer.
Onconase® (ranpirnase) – is a novel anti-cancer drug, in patients with unresectable or inoperable malignant mesothelioma.
Pemetrexed (Alimta®) – Alimta is the first drug to be approved specifically for malignant mesothelioma. It had about the same effectiveness of Taxotere in trials, but the side effects were much less severe.
Trimetrexate – Used in conjunction with luecovorin to treat pneumonia in patients with impaired immune systems (like cancer patients.)
Taxol® (Paclitaxel) – is given prior to Cisplatin/Carboplatin to decrease the incidence of severe neutropenia.
Zofran® (Ondansetron Hydrochloride) – is for the prevention of nausea and vomiting associated with single-day highly emetogenic cancer chemotherapy in adults.

Heat can also improve the efficacy of locally-administered chemotherapy agents. One method (Interoperative Hyperthermic Peritoneal Perfusion, or IHPP) uses a heated chemotherapy solution to irrigate the abdomen after surgery for peritoneal mesothelioma, to kill any malignancy left behind if the entire tumor is removed, or to slow the growth of any inoperable tumor or relieve symptoms in advanced stages of the disease.

Additional Oncology Drug Information:

Alemtuzumab (Campath™) – is indicated for the treatment of B-cell chronic lymphocytic leukemia (B-CLL) in patients who have been treated with alkylating agents and who have failed fludarabine therapy.
Amifostine (Ethyol®) – is an intravenous organic thiophosphate cytoprotective agent used to prevent certain unwanted side effects of a specific type of chemotherapy and radiation therapy when used to treat cancer.
Aprepitant (Emend®) – is a selective, non-peptide neurokinin-1 (NK1) receptor antagonist (also known as a substance P antagonist).
Aredia® – is for the treatment of osteolytic bone metastases of breast cancer, in conjunction with standard antineoplastic therapy.
Bevacizumab (Avastin™ ) – is a recombinant monoclonal antibody that binds to and inhibits the biological activity of vascular endothelial growth factor (VEGF).
Bleomycin – Sclerosing agent for the treatment of malignant pleural effusion and prevention of recurrent pleural effusions.
Bortezomib (Velcade) – is a reversible proteasome inhibitor.
Darbepoetin (Aranesp®) – is an erythropoiesis stimulating protein closely related to recombinant erythropoietin (Epoetin alfa). Darbepoetin stimulates the formation of red blood cells (RBC) by the same mechanism as endogenous erythropoietin.
Herceptin® (Trastuzumab) – is the first humanized antibody approved for the treatment of HER2 positive metastatic breast cancer.
Remicade® (infliximab) – is an antibody infusion treatment for Crohn’s Disease and Rheumatoid Arthritis.
Mylotarg® – is an antibody-targeted therapeutic agent that binds to the CD33 antigen found on the surface of myeloid leukemic cells of patients with Acute Myeloid Leukemia.
Neupogen® – is a human granulocyte colony-stimulating factor (G-CSF).
Oxaliplatin (Eloxatin™) – is a “third generation” platinum based antineoplastic agent. Oxaliplatin’s mechanism of action is similar to carboplatin and cisplatin as all are inhibitors of DNA synthesis but oxaliplatin is believed to have a different molecular target than cisplatin.
Palonosetron (Aloxi®) – is a selective 5-HT3 receptor antagonist. Due to its high potency and long half-life, palonosetron may be more effective in controlling delayed nausea and vomiting than other 5-HT3 RA.
Rasburicase (Elitek™) – is a recombinant urate-oxidase enzyme produced by a genetically modified Saccharomyces cerevisiae strain. Uric acid is the final step in the catabolic pathway of purines.
Rituxan® (Rituximab) – is indicated for the treatment of patients with relapsed or refractory, low-grade or follicular, CD20-positive, B-cell non-Hodgkin's lymphoma.
Temozolomide (Temodar®) – is an oral chemotherapeutic agent that is not directly active but undergoes rapid nonenzymatic conversion at physiologic pH to the reactive compound 3-methyl-(triazen-1-yl)imidazole-4-cardoxamide.
Zevalin® (Ibritumomab tiuxetan) – is a cancer therapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma.

Mesothelioma treatment with Immunotherapy

Like chemotherapy, immunotherapy agents like interferon and interleukin-2 can be administered either systemically or directly into the interpleural space. Using it in the interpleural space is a treatment that is most effective with Stage 1 disease.

Some of the agents used in immunotherapy are:

a-interferon
b-interferon
g-interferon
interleukin-2
lymphokine-activated killer cells

Studies show that patients in Stage 1 have a much higher rate of response to immunotherapy treatments.

Mesothelioma treatment with Photodynamic Therapy

A new approach used in connection with surgery for malignant mesothelioma is intrapleural photodynamic therapy. In this treatment, a light-activated photosensitizig drug is put in the pleural space, then light is used on the surface of the pleura to kill malignant tumor cells. The photosensitive compound is usually stable, but when it absorbs light in a particular wavelength, it kills tumor cells directly, and also by destroying the blood supply in the pleura. There can be complications – it can damage the area beyond the pleura. Photofrin II is the drug currently being evaluated for use.

Mesothelioma treatment with Gene Therapy

Phase 1 studies in gene therapy began in the late 1990s, and they show some promise in treating mesothelioma. There are various methods of gene therapy, some of which use a virus to carry the normal genetic material and replace the non-functional gene.

Gene therapy is still experimental, however, and there are no methods in general use. There are some problems with using gene therapy (including drawbacks to using virus cells as a vector) so it will be some time before this treatment is an option except in clinical trials.

Multimodal Therapy

Multimodal therapy is the combination of more than one therapy to treat malignancy. For example, surgery could be augmented with localized chemotherapy during the surgical procedure, then radiation therapy used afterward.

Because no single treatment has very much success in treating mesothelioma, multimodal treatments have been pursued as a way of increasing the effectiveness of treatment.

Treatment with Anti-cancer Medication

An anti-cancer drug approved by the FDA in 2003 called Iressa also shows some promise. It is the first drug of this type to be approved. It seems to work best after a patient has already been treated successfully – following chemotherapy, for example, instead of in conjunction with chemotherapy.

Treatment options for advanced malignant mesothelioma (Stages II, III and IV):

Many of the mesothelioma treatments used in advance stages of the disease are palliative – meant to relieve symptoms of the disease. Some of these are:

Symptomatic treatment of pleural effusion – This is the accumulation of fluid between the two layers of the pleura. It can cause difficulty breathing, so removing the fluid will make the patient more comfortable. In addition to draining the fluid, a treatment called pleurodesis can be used to keep additional fluid from accumulating. Pleurodesis involves inserting some mild irritant (like talc) into the pleural space to make it smaller, so fluid can’t collect there.
Pleurodesis can be performed at the bedside, or it can be done during a thorascopic procedure (where a scope – a narrow tube with a camera – is inserted into the chest cavity through a narrow incision), when the fluid can also be drained.
Palliative surgery – One surgical performed procedure as a mesothelioma treatment with Stage II, III and IV patients is pleurectomy, which strips the pleura and pericardium from the top to the bottom of the lungs. This can relieve some pain in the chest wall, and can also help prevent the recurrence of pleural efllusions. There are several possible complications, but when the disease recurs, it is more often local recurrence before distant metastasis.
Palliative radiation therapy – Radiation therapy can help reduce pain and pleural effusion.
Chemotherapy – Chemotherapy can also be used to provide some relief from symptoms, particularly in combination.
Intracavitary therapy – Used in advanced cases of mesothelioma, the use of chemotherapy agents locally in the pleural space or the peritoneum has produced some transient reduction in the size of the tumors and the buildup of fluid, according to some small-scale studies.

If distant metastasis has occurred (Stage IV), pain management and home care become more important.

Treatment of recurrent malignant mesothelioma:

Treatment for mesothelioma when it has recurred tends to be centered on methods that were not tried the first time around. These patients are often good candidates for phase I and II clinical trials for new forms of treatment.

“Results of a phase II trial of combined chemotherapy for patients with diffuse malignant mesothelioma of the pleura” Wiley InterScience Journal: Abstract,
http://www3.interscience.wiley.com/cgi-bin/abstract/75503750/ABSTRACT

“The Intraoperative Hyperthermic Peritoneal Perfusion Program” Web site of The University Hospital, Newark, NJ,
http://www.theuniversityhospital.com/ihpp/

“Malignant Pleural Mesothelioma: Characterization of MPM with Histochemistry, Immunochemistry, and Electron Microscopy” From the archives of Radiological Society of North America, http://www.rsna.org/REG/publications/rg/afip/privateM/1996/0016/0003/0613/6.htm

“Malignant Mesothelioma (PDQ): Treatment Option Overview” National Cancer Institute web site, http://www.cancer.gov/cancerinfo/pdq/treatment/malignantmesothelioma/patient/

“Overview of Therapies” NMT Brief (from CenterWatch) on Lung Cancer
CenterWatch web site,
http://www.centerwatch.com/bookstore/nmt/nmtb_lungcancer.pdf

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“FDA Approves First Drug for Rare Type of Cancer” from the Food and Drug Administration Web, http://www.fda.gov/bbs/topics/NEWS/2004/NEW01018.html

“Iressa May Stabilize Some Lung Cancers”, in CancerWise, published by the University Of Texas M.D. Anderson Cancer Center, July 2003, http://www.cancerwise.org/july_2003/display.cfm?id=65da7ac1-9c83-469c-acfd2a26fd45df5a&method=displayfull&color=green