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A mesothelioma treatment plan commonly includes one or several drugs that aim to stop the spread of cancer and shrink existing tumors. These medications may be used in combination with treatments like surgery and radiation therapy. This combination approach, called multimodal therapy, attacks the cancer in multiple ways for the best chance of killing cancer cells and shrinking tumors.
Each medicine falls into one of a few categories based on how it works against cancer – the main categories of mesothelioma medications are chemotherapy, targeted therapy, immunotherapy, photosensitizing and anti-angiogenesis. While many of these drugs are still in testing phases and are only available through clinical trials, some chemotherapy drugs have been approved by the U.S. Food and Drug Administration (FDA) for use in treating mesothelioma.
Chemotherapy is one of the most common treatments for any cancer, including mesothelioma. Chemotherapeutic agents seek out and attack cells that are rapidly dividing, which includes cancer cells. In spite of its well-known side effects, chemotherapy is considered one of the best mesothelioma treatment options.
A combination of the chemotherapy drugs cisplatin and pemetrexed has proven most effective for the majority of mesothelioma patients. This combination is the most common first-line chemotherapy for people with mesothelioma. If the drugs aren't tolerated well or aren't highly effective, second-line chemotherapy may be recommended. Second-line chemotherapy drugs may include gemcitabine, carboplatin, doxorubicin or Navelbine (vinorelbine).
Most chemotherapy drugs are synthetic, but Navelbine is actually semi-synthetic. Part of the drug is extracted from a flowering plant known as periwinkle. Navelbine may be administered alone or in combination with another chemotherapy drug such as gemcitabine.Learn more about chemotherapy and its use for mesothelioma patients
These are powerful drugs that also disrupt digestion. Some patients report stomach pain, vomiting, nausea and dark stools. Because of the potency of these drugs, a patient who develops a fever, chills, rash, swelling in the ankles of feet and blood in their urine should immediately contact their physician.
Targeted therapy is a growing field in cancer treatment that targets specific molecular alterations involved in cancer cell development, growth, metastasis and death. While chemotherapy affects both healthy and cancerous cells, targeted therapy affects cancerous cells exclusively.
NGR-hTNF is a targeted therapy drug that is currently in Phase III trials to determine its efficacy as a management therapy for people with recurring mesothelioma. The first study of NGR-hTNF, which started in 2007, tested the drug's efficacy in 57 pleural mesothelioma patients. Some patients in the Phase II trial previously received another form of treatment. However, all prior treatments were ineffective and concluded months before patients received NGR-hTNF. Initially, NGR-hTNF was delivered intravenously for one hour every three weeks. In later testing, the trial was amended to treat patients every week. About half of the study's patients lived a year or longer after NGR-hTNF treatment. The Phase III trial is ongoing.
Another form of targeted therapy that was tested in clinical trials on mesothelioma patients is the drug Onconase (ranpirnase). The drug is among the few therapies that progressed all the way to a Phase III clinical trial. Though early results were promising, preliminary Phase IIIb clinical trial results showed that Onconase did not improve overall survival enough for the FDA to award approval. Further clinical trials on Onconase for mesothelioma were discontinued.
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Following the Onconase trials, mesothelioma researchers — among them Dr. Michele Carbone and Dr. Harvey Pass — performed a study on mesothelioma cell lines in 2011 to see whether ranpirnase could be more effective in mesothelioma patients with low levels of the protein kinase enzyme Akt. Results from the study suggest that ranpirnase could provide slight therapeutic benefit to that group, though no further studies have been conducted to investigate this potential in humans.
Immunotherapy agents are used in mesothelioma patients to enhance the patient's own immune system and help the body to attack cancer cells. A healthy immune system does not fight cancer because it does not recognize cancer cells as foreign. But with the addition of immunotherapy medications, the immune system may better recognize the difference between healthy cells and cancerous cells, and begin fighting the cancer.
Amatuximab (also known as MORAb-009) is an immunotherapy drug that was tested on mesothelioma patients in Phase I and Phase II clinical trials. Despite promising results in the Phase I trial, the Phase II trial showed that not enough mesothelioma patients responded to the drug to warrant further study. The overall median survival was 14.8 months.
The drug SS1(dsFv)-PE38 (called SS1P for short) is an immunotoxin. This type of drug combines immunotherapy's tumor-honing properties with a toxin so that it specifically targets cancer cells and then kills them. An ongoing Phase I study of SS1P in people with pleural mesothelioma has thus far reported a partial tumor response in 12 out of 20 participants.
In addition to their ability to recruit the immune system in the fight against cancer, immunotherapy drugs are appealing because they have milder side effects than chemotherapy.Learn more about immunotherapy
Photodynamic therapy is a two-step treatment procedure that uses photosensitizing drugs to make cancer cells vulnerable to light and then uses light to destroy the cancer cells. For mesothelioma patients, the photosensitizer is almost always Photofrin (porfimer sodium), which is also used in other cancers like esophageal cancer.
Photodynamic therapy is being tested in pleural mesothelioma patients and has been found to improve survival times. The treatment is still in development for peritoneal mesothelioma while doctors search for an effective means of administering light to the abdominal cavity. The treatment commonly causes light sensitivity for about six weeks, which may result in burning, swelling or scarring.Learn more about photodynamic therapy results in mesothelioma
Scientists continue the search for effective drugs to help prevent angiogenesis, a normal function that allows the body to heal itself by creating new blood vessels. The process also builds vessels to tumors, feeding them with a fresh supply of blood and allowing them to grow and spread.
Researchers believe that stopping this process may be the key to stopping the aggressive nature of mesothelioma, not to mention the spread of many other types of cancer. Angiogenesis also is a necessary precursor to metastasis, which is the process of cancer cells spreading from one area of the body to another.
Drugs that could inhibit the formation of new blood vessels to tumors are called anti-angiogenesis drugs. These include bevacizumab, interferons and interleukin-12. Without blood vessels to bring nutrients, the cancer cells are unable to divide and spread, and eventually die.
But stopping angiogenesis is not the hard part. The hard part is stopping angiogenesis related to cancer without hindering the body's natural ability to heal itself. This is extremely difficult and is at the center of considerable research.
Clinical trials are testing more than 20 drugs with various cancers — all with the same goal.
Combined with other treatments like chemotherapy and radiation, these drugs are producing impressive results among mesothelioma patients in clinical trials. The drugs, including semaxanib (SU5416), thalidomide and tetrathiomolybdate, show much improved survival rates.
Angiogenesis occurs by means of a complex "signaling cascade" in which cells communicate messages via proteins. Anti-angiogenesis drugs interfere with this process in one of three ways, each corresponding to a specific step of the cascade.
The first step of the angiogenesis process makes room for new endothelial cells, which are located on the outer lining of blood vessels. In this step, endothelial cells break down placeholder material surrounding the cells, called the extracellular matrix.
Cancer cells trigger this process to create space for a new blood vessel to branch off an existing one toward a tumor. When anti-angiogenesis drugs like marimistat and neovastat inhibit this process, new cells have no room to form blood vessels, preventing the angiogenesis cascade.
In one study, 26 pleural mesothelioma patients received chemotherapy alongside anti-angiogenesis drugs. Patients had a median survival of 17 months, notably longer than the typical mesothelioma survival of four to 12 months.
Anti-angiogenesis drugs tend to cause fewer and milder side effects than chemotherapy. Whereas chemotherapy drugs attack quickly dividing cells even if they are healthy, anti-angiogenesis drugs don't affect most healthy cells.
The downside is that because angiogenesis occurs when wounds are healing, these drugs complicate the healing process and may lead to excessive bleeding. Patients may also develop blood clots in the arteries, internal bleeding or a hole in the digestive tract.
Overall, angiogenesis-targeting therapies have a low risk of major side effects while showing good results in preventing mesothelioma metastasis.
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