Mesothelioma Drugs: Medications for Mesothelioma
Mesothelioma drugs can extend life expectancy and improve the quality of life for mesothelioma patients. Though no cure currently exists for mesothelioma, new drug treatments are continually being tested in clinical trials at mesothelioma treatment centers.
Mesothelioma is cancer of the lining surrounding the lungs, stomach, heart, or testicles. It spreads rapidly and is difficult to treat. Surgical approaches offer some patients a longer life expectancy, but mesothelioma is often diagnosed at later stages after it has become inoperable.
Drug therapy is the primary option for inoperable mesothelioma. It is also generally used in patients who receive surgery. Mesothelioma medications aim to increase life expectancy and relieve symptoms such as pain, shortness of breath, coughing, and weight loss.
Though some medications have been effective in shrinking tumors and slowing their progression, the prognosis for mesothelioma remains poor, with a life expectancy of 15 to 22 months and a five-year survival rate of less than 20 percent for pleural mesothelioma patients.
Is mesothelioma curable?
Currently, no known cure for mesothelioma exists. However, numerous drug studies are underway, and some have shown promising potential.
Novel drug treatments are experimental or off-label treatments that are not officially approved by the Food and Drug Administration (FDA). Some mesothelioma doctors use novel drug treatments with positive results, though these results still fall short of curing mesothelioma.
Dr. Robert Cameron of the Pacific Mesothelioma Center in Los Angeles treats mesothelioma as a chronic condition requiring management (much like high blood pressure or diabetes) rather than attempting to cure it. He has had remarkable success increasing the life spans of his patients well beyond five years using a combination of surgery and novel drugs.
Mesothelioma Therapy Drugs
Mesothelioma therapy drugs can slow the progression of mesothelioma, increasing a patient’s life expectancy. They include chemotherapy, immunotherapy, and targeted drug therapies.
The FDA has approved just one combination of chemotherapy drugs for mesothelioma. However, some practitioners have had success substituting drugs or adding to this regimen, and clinical trials are studying new mesothelioma chemotherapy drugs.
Pemetrexed and Cisplatin
The sole FDA-approved chemotherapy regimen for mesothelioma is the combination of pemetrexed and cisplatin. It received approval on February 4, 2004, based on the results of a Phase III study that found a statistically significant improvement in treatment response and overall survival for the combination of the two drugs, compared to cisplatin alone.
These drugs are administered intravenously in 21-day cycles. This means that you’ll go to an infusion center once every 21 days to receive your chemotherapy medications. It generally takes a few hours to complete the infusion of the drugs. The day that you receive your medications is considered the first day of that cycle of chemotherapy.
In general, the dose of chemotherapy drugs is based on a person’s body size. It’s measured in mg/m2, with m being the patient’s height in meters and mg being milligrams of the drug. The FDA’s recommended drug schedule is as follows:
- Pemetrexed: 55 mg/m2 on Day One of each 21-day cycle
- Cisplatin: 75 mg/m2 beginning 30 minutes after pemetrexed is administered
This dose is generally used as a starting point. Your doctor may adjust your dose based on how your cancer responds, as well as on any side effects that you experience. The therapy may be discontinued completely if the side effects are too severe.
Cisplatin
Cisplatin is marketed under the brand names Platinol and IntraDose. It is in a class of drugs known as platinum-based chemotherapy drugs, which means that the compound contains a molecule of platinum. This molecule binds to DNA, blocking the cell’s access to its own genetic material. Barnett Rosenberg, Ph.D., a biophysics researcher at Michigan State University, discovered cisplatin by accident in 1965. It first gained FDA approval in 1978.
According to the National Cancer Institute, cisplatin works by inhibiting cell division. Though effective, it is also highly toxic and may cause severe side effects, including kidney damage.
Pemetrexed
Pemetrexed is marketed under the brand name ALIMTA. Overall, it is less toxic than cisplatin. Pemetrexed works by blocking certain enzymes that are necessary for the replication of DNA. Cells need to replicate their DNA in order to divide, and cancer cells are generally dividing rapidly, leading to the growth of the tumor.
The most significant adverse effect of pemetrexed is the severe depletion of folate, which is one of the B vitamins. As a result, folate and Vitamin B12 injections are required components of treatment, to help reduce side effects. These injections should start at least one week before the first cycle of pemetrexed and continue for at least three weeks after the last cycle.
Alternative Chemotherapy Drugs for Mesothelioma
Although the combination of cisplatin and pemetrexed is usually considered to be the first-line chemotherapy treatment for pleural mesothelioma, other chemotherapy drugs are sometimes used to treat the disease. There are several types of chemotherapy that have shown some evidence of effectiveness in studies.
Carboplatin is another platinum drug that is sold under the brand name Paraplatin. It is generally less toxic than cisplatin and yields similar overall survival results when used alongside pemetrexed for mesothelioma treatment. Carboplatin is often used as a substitute for patients who experience severe side effects from cisplatin or who are considered more vulnerable to such side effects.
Antimetabolite drugs mimic the molecules cancer cells normally use for reproduction, which interferes with the cells’ ability to divide. Pemetrexed is an antimetabolite, and there are also other antimetabolite drugs that may be used along with platinum-based chemotherapy drugs. One example is raltitrexed, marketed as Eloxatin.
One study found that the combination of cisplatin with raltitrexed every 21 days performed better than cisplatin alone, and showed a similar benefit to the pemetrexed/cisplatin combination, without a deterioration in the quality of life. As a result, raltitrexed is sometimes used instead of pemetrexed.
Another antimetabolite, gemcitabine, has been shown to have effects on the immune system that could be beneficial in treating some types of cancer. Research is still investigating the best ways to use this drug. The use of gemcitabine for treating mesothelioma is uncommon, but it may be used in certain patients. It may be used alongside cisplatin or carboplatin in patients who are not candidates for receiving pemetrexed or raltitrexed.
Plant alkaloids are chemotherapy agents that were originally derived from certain plants. One example is vinorelbine, which is derived from the periwinkle plant, according to Chemocare. It is sold under the brand name Navelbine. According to a scientific review published in the Journal of Thoracic Disease, vinorelbine administered once weekly as a first-line treatment showed promising results in mesothelioma patients.
Another plant alkaloid is irinotecan, marketed under the brand name Camptosar. This drug is derived from the Asian “Happy Tree” (Camptotheca acuminata), and has been studied as a second-line treatment option for mesothelioma in conjunction with other drugs.
Antitumor antibiotics are a type of chemotherapy that alters the way that DNA is replicated inside of cells, which prevents cells from dividing normally. This class includes several specific agents, such as mitomycin and doxorubicin. Research has yet to identify a clinical benefit to using these drugs in mesothelioma patients, but they are still being studied for potential use in combination with other drugs.
Hyperthermic Intraperitoneal Chemotherapy
Also known as HIPEC, hyperthermic intraperitoneal chemotherapy is a type of targeted chemotherapy used in conjunction with surgery to treat peritoneal mesothelioma. During the surgical procedure to remove tumors from the abdomen, chemotherapy drugs are heated and perfused into the abdominal cavity. They’re left there for a period of time and then are washed out prior to closing the surgical incisions.
The most common drug used for HIPEC is cisplatin, but there is no universal standard for HIPEC drugs, according to Cancer Management and Research. The following may also be used in HIPEC:
- Cisplatin and mitomycin
- Cisplatin and doxorubicin
- Mitomycin alone
Peritoneal mesothelioma patients who undergo HIPEC experience an estimated median survival time of 34 to 92 months and a five-year survival rate between 29 and 59 percent.
Second-Line Chemotherapy Treatments
If the cancer doesn’t respond to the first type of chemotherapy used, or if this treatment is not effective enough, then a different type of chemotherapy may be tried next. This is known as second-line chemotherapy.
No second-line chemotherapy drugs have been specifically approved for mesothelioma. This does not necessarily indicate that second-line chemotherapy is ineffective. There are very limited scientific data on this topic, making it difficult to evaluate the effectiveness of second-line chemotherapy.
One study published by Lung Cancer found that the use of gemcitabine combined with vinorelbine as second-line or third-line therapy for pleural mesothelioma had very little impact on patients’ survival.
These results are consistent with data published by BMC Cancer, which found that second-line chemotherapy had only a very small impact on survival. In these studies, patients received one of the following drug regimens during second-line treatment:
- Pemetrexed plus a platinum drug
- Gemcitabine
- Taxane
- The immunotherapy drug nivolumab
The role of second-line chemotherapy in treating mesothelioma remains unclear, but it is used in some patients. There are a very few studies on this type of therapy, and research into various forms of second-line chemotherapy is ongoing.
Chemotherapy Side Effects
The side effects from chemotherapy vary from one patient to the next, with some patients noticing only a few mild side effects and others experiencing severe reactions. There can be long-term or even permanent effects from chemotherapy, so it is important to discuss the risks and benefits before committing to treatment.
If you experience side effects, it is important to report them to your doctor. Medication may be available to reduce or eliminate these effects. Side effects may include:
- Fatigue
- Loss of hair
- Unexplained bruising
- Infections
- Anemia
- Nausea
- Vomiting
- Changes in appetite
- Diarrhea or constipation
- Mouth sores
- Swallowing difficulties
- Tingling, numbness, or pain in the extremities
- Dry skin
- Kidney problems
- Weight loss
- Brain fog
- Depression or anxiety
- Sexual dysfunction
Chemotherapy drugs can interact with certain vitamins and supplements. You should discuss any over-the-counter medications or supplements with your treatment team before you take them. Some may be unsafe to use while on chemotherapy, and others can reduce the effectiveness of chemotherapy treatment.
Immunotherapy Drugs
Immunotherapy drugs work by helping the body’s own immune system attack cancer cells. Mesothelioma specialists often use immunotherapy drugs in conjunction with chemotherapy for maximum benefit.
Many immunotherapy drugs are monoclonal antibodies. These antibodies are produced in a lab, and they can very precisely target specific proteins in order to achieve a certain response.
Opdivo is the brand name for nivolumab, an immunotherapy drug often combined with chemotherapy and other immunotherapy drugs. It works by helping T cells, a type of white blood cell, to recognize and attack cancer cells.
T cells fight infection by attacking cells that they perceive as invaders. These cells contain a checkpoint protein called programmed death receptor-1 (PD-1), which helps T cells differentiate between healthy cells and invading organisms. It creates proteins found on the surface of healthy cells that tell T cells not to attack them.
Unfortunately, many cancer cells also contain these proteins, essentially disguising themselves as healthy cells, so the T cells leave them alone.
Opdivo is a monoclonal antibody targeted to PD-1. It works by disrupting the function of this protein, preventing cancer cells from disguising themselves as healthy cells. This allows the patient’s T cells to attack the cancer.
A potential complication of doing this is that it may also impact how T cells respond to healthy cells, resulting in the body attacking its own healthy tissues. This can occur in any part of the body during or after treatment, including internal organs. It can lead to life-threatening complications.
Yervoy is the brand name for another immunotherapy drug, ipilimumab. Like Opdivo, Yervoy is also a monoclonal antibody. However, it targets a different substance, the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). This helps to increase the ability of T cells to divide, which amplifies the immune response.
When Yervoy is combined with Opdivo, the patient benefits from a combination of effects. The immune system is upregulated, and cancer cells have a more difficult time hiding from T cells. This maximizes the number of cancer cells that the patient’s immune system can detect and destroy.
In 2020, the FDA approved the combination of Opdivo and Yervoy as a first-line treatment of inoperable mesothelioma—the first drug regimen approved for first-line treatment of inoperable mesothelioma in 16 years. Before that, the only approved systemic mesothelioma therapy was the chemotherapy combination of pemetrexed and cisplatin.
Clinical studies leading to its approval found an increased overall survival of 18.1 months, compared to 14.1 months for patients who underwent standard chemotherapy.
The most common side effects associated with immunotherapy include the following:
- Fatigue
- Musculoskeletal pain
- Rash
- Diarrhea
- Shortness of breath
- Nausea and vomiting
- Reduced appetite
- Coughing
- Itching
- Abdominal pain
- Upper respiratory infections
- Headaches
- Hypothyroidism
- Weight loss
- Dizziness
Pembrolizumab, marketed under the brand name Keytruda, is another monoclonal antibody that targets the PD-1 pathway. The FDA has approved Keytruda for use in mesothelioma patients who are not eligible for surgery and who have no good alternative treatment options.
A study published in the Lancet showed that this drug may offer a survival benefit in some patients, although the cancer often does not respond to the treatment. It can also cause severe side effects, much like other types of immunotherapy.
Other types of immunotherapy are currently being studied, and there have been some promising results. A study published in the journal Clinical Cancer Research showed that another monoclonal antibody known as amatuximab showed a small increase in overall survival with very few side effects. This drug targets a specific protein that’s present at high levels on the surface of mesothelioma cells.
Other monoclonal antibodies are being studied for their potential effects on mesothelioma. In the future, there may be more immunotherapy options available for treating this disease.
Researchers are currently investigating cancer vaccines in clinical trials, and some results have been positive.
Cancer vaccines help to sensitize the immune system to proteins that are produced by cancer cells. Much like a vaccine against a virus teaches the immune system what the virus looks like so that it can attack it more effectively, a cancer vaccine teaches the immune system what cancer looks like, encouraging the immune system to attack and destroy cancer cells.
To accomplish this, researchers alter naturally occurring viruses. When injected, the altered viruses sensitize the immune system to cancer cells. Some of the cancer vaccines that have shown promise in early studies include:
- The Edmonston vaccine strain of the measles virus which leads to damage to the membranes of cancer cells, causing them to die
- The TWIST1 vaccine, which causes an increased T cell immune response
- The TroVax vaccine, a pox virus-based vaccine that yielded positive results when combined with chemotherapy in a clinical trial
Antiangiogenesis drugs inhibit the growth of new blood vessels. Cancer cells need to establish a blood supply in order to get the energy and nutrients that they need to grow. Blocking the formation of new blood vessels helps to prevent the cancer cells from doing this, limiting their ability to divide and grow.
The most studied antivascular drug is bevacizumab, marketed and sold as Avastin. This is a monoclonal antibody, which targets a particular protein that’s necessary for the formation of new blood vessels.
According to a study published in the Lancet, this drug significantly increased the survival time of patients when combined with the chemotherapy drugs pemetrexed and cisplatin.
Other antiangiogenesis drugs that are currently under study include:
- Nintedanib, which is also used with pemetrexed/cisplatin
- Ramucirumab, which may directly decrease tumor growth and is being studied for its effects when combined with gemcitabine
- Imatinib, which may increase the efficacy of gemcitabine, although no beneficial effects were observed with pemetrexed
- Asparagine-glycine-human tumor necrosis factor-alpha (NGR-hTNF), which increases chemotherapy uptake into the cells
Photodynamic therapy is a novel cancer treatment that includes the administration of a drug that is activated by a specific wavelength of light, according to the American Cancer Society. These drugs are known as photosensitizing agents, and they work by forming a special type of oxygen molecule that kills cancer cells. Because the drug is inactive unless it’s exposed to light, most of the body’s tissues are protected from the effects of the therapy, which minimizes side effects. However, the person will be more sensitive to sunlight for a period of time after the treatment, and will need to be careful about sun exposure.
For solid tumors like mesothelioma, the drug used is generally porfimer sodium (marketed as Photofrin).
The advantages of photodynamic therapy are significant:
- No long-term side effects when properly administered
- Precise targeting of cancer cells
- Repeatable multiple times at the same site if needed (unlike radiation therapy)
- Lack of scarring after the site heals
One of the disadvantages of photodynamic drugs is they only work in areas where light can reach. Mesothelioma is deep inside the body, outside the reach of light. However, for pleural mesothelioma patients, PDT can be used during surgery while the chest is open. This procedure is known as intraoperative photodynamic therapy.
Before surgery, the patient intravenously receives Photofrin, which is absorbed by both healthy and cancerous cells. The drug tends to preferentially accumulate in cancer cells due to their higher rates of metabolism. During surgery, after tumors are removed, light is applied using a laser to activate the drug and kill any remaining mesothelioma cells.
A study published in Photochemical Photobiology evaluated the use of photodynamic therapy with chemotherapy following a surgical procedure known as extended pleurectomy/decortication. Researchers found improved overall survival in very advanced mesothelioma cases.
This treatment is still considered experimental for mesothelioma patients and is being studied in clinical trials. However, some mesothelioma centers, including the Roswell Park Comprehensive Cancer Center, use photodynamic therapy to treat pleural mesothelioma.
Palliative Drugs for Mesothelioma
Mesothelioma takes a considerable toll on the overall health and well-being of patients and their families. Palliative care aims to relieve the physical and psychological effects of the disease, as well as treatment side effects. In some cases, palliative care also extends to family caregivers, offering them mental health support in coping with their loved one’s illness and the demands of caregiving.
Pain Management
Pain management is a high priority in palliative care for mesothelioma patients, who typically experience pain from multiple sources, according to Lung Cancer: Targets and Therapy.
In mesothelioma patients, pain may originate from one or more of the following:
- Tumors invading the bones, soft tissue, and skin
- Tumors invading internal organs
- The body’s inflammatory response to mesothelioma or its treatment
- Neuropathic pain, which results from damage to the nervous system (such as a tumor pressing on a nerve)
Pain from a combination of these sources can be severe and challenging to control.
The World Health Organization recommends starting with the least potent pain medications and gradually stepping up to stronger medications as needed, evaluating the patient’s pain at each step. This is known as the Analgesic Ladder for Cancer Pain Relief. The goal is to use the least amount of pain medication that is effective.
The steps are:
- Step 1: Non-opioids and adjuvants
- Acetaminophen (also known as paracetamol)
- NSAIDs, such as aspirin and ibuprofen
- Step 2: Opioids for mild to moderate pain, combined with adjuvants and non-opioids
- Codeine
- Tramadol
- Step 3: Opioids for moderate to severe pain with non-opioids and adjuvants
- Morphine
- Oral, sustained release, if possible
- If oral administration is impractical, the administration may be by injection or a transdermal patch
- Oxycodone
- Hydromorphone
Medications should be given orally for as long as possible at regular intervals.
Studies have shown that this approach relieves cancer pain in up to 80% of patients. However, some of the specifics have been questioned, and some cancer experts advocate moving directly from Step 1 to Step 3 (skipping the use of weak opioids and moving directly to strong opioids). Ultimately, a doctor’s clinical judgment will be used in determining the best approach for a particular patient.
What are adjuvants?
Adjuvant pain medications are drugs that have other medical uses with a secondary effect of relieving pain, according to the American Journal of Hospice & Palliative Care. Adjuvants commonly prescribed for cancer pain management include:
- Antidepressants
- Anticonvulsants
- Local anesthetics
- Topical agents
- Steroids
- Bisphosphonates
- Calcitonin
The most commonly used adjuvant drugs are tricyclic antidepressants and antiepileptic drugs such as gabapentin and pregabalin, according to Lung Cancer: Targets and Therapy.
Several studies suggest the benefits of adjuvants for pain relief are minimal, and if benefits are not observed within four to eight days, increasing the dose is unlikely to help.
Nerve injections, commonly known as nerve blocks, may be administered in the most severe cases when conventional pain management has proven insufficient. In such situations, a local agent is applied to destroy the nerve and eliminate the source of pain.
Shortness of Breath
Shortness of breath, also known as dyspnea or air hunger, is a distressing symptom commonly experienced by mesothelioma patients, and it may feel like suffocation.
An expert panel of the American Society of Clinical Oncology recommends using medications only if non-pharmacological options are ineffective. When medication is needed, opioids are recommended. Corticosteroids and benzodiazepines may be added if opioids alone are insufficient.
Opioids should be regularly scheduled and offered orally unless this is impractical, in which case administration by injection is recommended. Additional opioids may be necessary before exertion, which generally increases shortness of breath.
If airway obstruction contributes to breathlessness, systemic corticosteroids may be recommended. Bronchodilators may be ordered if the muscles in the airways experience spasms that block your airway, or if your doctor determines you have other types of pulmonary obstructions that could be relieved with bronchodilators.
In the most severe cases of shortness of breath, continuous sedation may be offered when no other treatments are effective, especially when the life expectancy is down to just a few days.
Weight Loss
Weight loss may occur for a variety of reasons in cancer patients, according to the MD Anderson Cancer Center. Patients often eat significantly less due to malaise, pain, inflammation, or depression, according to the MD Anderson Cancer Center. The body’s attempts to manage cancer can also increase metabolism, resulting in an increased demand for energy. Chemotherapy’s side effects may include nausea and mouth sores, both of which make eating difficult. Certain types of cancers or cancer treatments can also affect testosterone levels in men, which can also contribute to weight loss.
Dramatic weight loss can have severe negative effects on treatment response, and it is significantly more difficult to reverse than to prevent. The following medications may assist with preventing weight loss.
- Beta-blockers for hypermetabolism
- Antiemetics for nausea and vomiting
- Anxiety medication in conjunction with counseling
- Antidepressants
- Anti-inflammatories
- Hormonal supplements to replace testosterone in males
Nausea and Vomiting
In mesothelioma patients, nausea and vomiting may occur for a variety of reasons. They may represent mesothelioma symptoms (particularly in peritoneal mesothelioma patients) or treatment side effects (such as from chemotherapy).
Medications that relieve nausea and vomiting are known as antiemetics. They can work based on multiple mechanisms.
Selective serotonin receptor antagonists remedy nausea and vomiting by blocking the effects of serotonin at a specific type of receptor (the 5-HT3 receptor). They are often provided before chemotherapy and during the days that follow. Examples of serotonin antagonist drugs include:
- Ondansetron
- Granisetron
- Dolasetron
- Palonosetron
NK-1 receptor antagonists work by blocking the vomiting reflex in the brain. These medications are often combined with other anti-nausea medications and include:
- Aprepitant
- Rolapitant
- Fosaprepitant
Dopamine antagonists may be given when other drugs fail to work. They work by targeting dopamine in the brain to prevent it from binding to areas of the brain that trigger nausea and vomiting. However, they carry a high potential for side effects, such as sedation. The most common dopamine antagonists include prochlorperazine and metoclopramide.
The following drugs typically prescribed for other uses may also be effective in controlling nausea and vomiting:
- Steroids such as dexamethasone
- Benzodiazepines, such as lorazepam and alprazolam, may ease the anxiety that can contribute to nausea and vomiting
- Cannabinoids, the active ingredient in marijuana, may stimulate appetite
- Olanzapine, an atypical antipsychotic often used in dementia care, has been shown to reduce nausea and vomiting
Depression and Anxiety
Depression and anxiety are common symptoms in patients with mesothelioma and tend to worsen in inpatient settings. According to Frontiers in Psychology, these conditions can negatively affect treatment response and compliance, and they can also have a significant impact on a person’s quality of life.
Depression Medications
The most common depression drugs for cancer care include:
- Selective serotonin reuptake inhibitors (SSRIs)
- Zoloft
- Celexa
- Prozac
- Paxil
- Tetracyclic antidepressants: Remeron
- Tricyclic antidepressants: Elavil
Zoloft and Celexa are often recommended due to their decreased likelihood of interactions with chemotherapy, and most patients tolerate them well. However, it’s important to use caution when taking antidepressants along with chemotherapy, particularly when white blood cell levels and/or platelet levels are low. Most antidepressants can also worsen nausea and vomiting caused by chemotherapy, so they may not be a good choice for some patients.
Counseling can also be helpful for many cancer patients, as well as their caregivers, without the risk of side effects. A therapist can help you to learn ways of coping with your diagnosis and its associated challenges. Some patients find it helpful to use methods like meditation or biofeedback.
Anxiety Medications
Anxious feelings are natural when facing mesothelioma, but medication may be warranted when these feelings adversely impact your daily life and create physical effects such as chest pain and sleep changes. The following antianxiety medications may be prescribed:
- Ativan
- Valium
- Klonopin
- XANAX
- Thorazine
- BuSpar
- Haldol
Counseling may also be helpful for patients with anxiety. Antianxiety medications can cause side effects and have the potential to be addictive, so it may be beneficial to try other methods of dealing with anxiety first, before reaching for medications.
Hope for a Cure
Though mesothelioma drugs can relieve symptoms and extend life, a mesothelioma cure has yet to be discovered. However, researchers continue to develop increasingly effective mesothelioma drug treatments through numerous clinical trials worldwide.
If you have been diagnosed with mesothelioma, you may be entitled to substantial compensation. Contact our experienced mesothelioma lawyers today to schedule a free consultation.
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