Chemotherapy is an important part of any mesothelioma treatment regimen. While there is no cure for mesothelioma, chemotherapy can offer a variety of benefits for patients suffering from this terrible affliction.
The treatment option involves administering medications (usually at least 2 and possibly more) that can help eliminate cancer cells and reduce tumor size. It is often combined with radiation therapy and surgery in a multimodal treatment approach. Over 70% of mesothelioma patients engage in some type of treatment.
Chemotherapy can be used in one of three ways:
- Neoadjuvant – administered prior to surgery to shrink and soften tumors and make them easier to excise
- Intraoperative – administered during a surgical procedure directly on the tumor location
- Adjuvant – administered post-surgery to eliminate remaining cancer cells
Basics of Chemotherapy
In some cases, chemotherapy can be administered as a palliative treatment. Palliative treatments are given with the express purpose of alleviating symptoms and not necessarily extending lifespans.
As tumors grow, they can begin to impinge and put pressure on other organs and tissues, causing a wide range of pain for the patient. If surgery is not an option, then mesothelioma chemotherapy drugs can help reduce the size of the tumor and thereby mitigate some of the pain.
Chemotherapy is also used as a curative treatment to help improve prognoses and extend lifespans. Again, with this approach, it is most often combined with surgery and radiation therapy for optimal results.
Medications are usually administered in one of two ways: systemic or intraoperative. Systemic treatments are more traditional and are usually administered by IV directly into the bloodstream.
In some cases, you can also take chemotherapy pills, but those are usually only available during clinical trials. As mentioned above, intraoperative chemotherapy options are usually administered directly at the tumor location during open surgery. With this method, the drugs are heated to as high as 109 degrees Fahrenheit to maximize efficacy.
When chemotherapy is administered systemically, doctors may try several combinations of drugs. The first attempt is referred to as a first-line chemotherapy treatment. If that doesn’t work or if the physician feels as if a separate dose of different drugs will work better, then they may administer a second-line chemotherapy treatment. This continues for third-line, fourth-line, and beyond as needed.
Each round of chemotherapy treatments involves a “cocktail” of drugs and is typically administered every few weeks for several months.
Success Rates of Chemotherapy for Mesothelioma
When used as a curative treatment, chemotherapy has shown greatly improved survival rates even when it is used as the only treatment method. With no treatment whatsoever, median survival for most patients is only around 4 months. If you add just one line of chemotherapy, median survival increases to 1 year. Two lines of mesothelioma chemotherapy can produce a life expectancy of 16 months.
For optimal results, however, it’s necessary to combine chemotherapy with other treatment options. Surgery is the most effective way to remove tumors and cancerous cells, but, as neoadjuvant therapy, chemotherapy can make surgeries easier by shrinking and softening those tumors. Chemotherapy and radiation therapy are also vital for killing the remaining cancer cells after surgery has been completed.
With all three treatment methods, the 2-year survival rate is at 51%, meaning that over half of the people who engage in chemotherapy, surgery, and radiation therapy survive for 2 years or more. With just chemotherapy and surgery, that 2-year survival rate is only 29%. So, it’s clear that most mesothelioma chemotherapy is good, and it’s even better when combined with other treatment methods.
One intraoperative chemotherapy treatment known as hyperthermic (heated) intraperitoneal chemotherapy (HIPEC) has greatly increased survival rates for peritoneal mesothelioma. The peritoneal form of the disease is the second most common (behind pleural mesothelioma) and occurs in the lining of the abdominal cavity. HIPEC has brought 5-year survival rates for that form of the disease to over 50%.
Let’s now look at some of the chemotherapy drugs most commonly used to treat mesothelioma.
Pemetrexed (which is sold under the brand name, Alimta) was the first chemotherapy drug ever approved by the U.S. Food and Drug Administration (FDA) for treating mesothelioma. It is currently the only drug officially approved by the FDA for mesothelioma treatment. Even so, it is most often used as first-line therapy in conjunction with cisplatin, another chemotherapy drug.
With cisplatin, pemetrexed has produced a median survival time of around 16 months for most patients. Doctors typically prescribe vitamin B9, vitamin B12, and/or folic acid to avoid harsh side effects.
As mentioned above, cisplatin is often used as a first-line treatment with pemetrexed. It is a platinum-based drug that was first made available for chemotherapeutic use in 1978. For patients who are not good candidates for surgery because of the advanced stage of the disease, cisplatin is sometimes administered by itself.
Unfortunately, because cisplatin is an older chemotherapy drug, its side effects are usually more severe. It can affect kidney function, produce increased nausea, and deplete nutrition stores.
Gemcitabine is one of the most recent mesothelioma chemotherapy drugs to come into use, and it works by substituting itself for nucleic acids during DNA replication. It is often combined with platinum-based drugs like cisplatin or carboplatin. It can also occasionally be combined with pemetrexed.
The drug is used as either a first- or second-line treatment in most cases. Its efficacy in treating mesothelioma is still up for debate, but some studies have shown that it maintains disease stability in about 46% of cases. It is particularly helpful in late-stage mesothelioma.
Carboplatin is another platinum-based drug that is similar to cisplatin. Unlike cisplatin, however, carboplatin’s side effects are typically not as harsh. The drug is commonly used as a first- or second-line treatment and is often paired with gemcitabine and sometimes pemetrexed. Carboplatin is often used for mesothelioma that does not respond to cisplatin.
Typically used to treat non-small cell lung cancer, vinorelbine has also proven effective as a treatment for mesothelioma. The drug is a plant alkaloid that works by enacting programmed cell death (apoptosis) in cancer cells. It is often combined with cisplatin and has been used as a first-line or second-line treatment. It has also been used in patients who have had a recurrence of the disease.
When used as a first-line treatment with cisplatin, the drug saw a median survival rate of 17 months in patients with stage 4 mesothelioma.
New Chemotherapy Drugs for Mesothelioma
Clinical trials are always ongoing. The research into these new chemotherapy drugs for mesothelioma is still inconclusive, but many of them are showing promise.
Some of these new chemotherapy drugs include:
- Bevacizumab (Avastin)
- Ranpirnase (Onconase)
- Raltitrexed (Tomudex)
Bevacizumab is an immunotherapy drug that works by blocking the formation of new blood vessels where tumors can form. It has yet to be approved by the FDA and is most commonly used in the treatment of colorectal cancer. Still, it has shown some efficacy in treating mesothelioma in clinical trials. The drug has been combined with pemetrexed and cisplatin as a treatment for late-stage mesothelioma. It may also be effective for patients whose tumors are inoperable.
Ranpirnase (sometimes referred to as the P-30 protein) is an enzyme and another experimental drug for mesothelioma. The contents of the drug are actually retrieved from northern leopard frog embryonic stem cells and eggs. It works by breaking down the cancer cells’ RNA and is often combined with doxorubicin. Clinical trials testing ranpirnase’s efficacy with mesothelioma are still ongoing.
Raltitrexed is another experimental drug that interferes with the DNA replication of most cancer cells. It has been approved for use in treating colorectal cancer but has also shown some positive results in clinical trials for mesothelioma. It is usually combined with cisplatin for best results.
Often used in conjunction with cisplatin or paclitaxel, doxorubicin is a drug that has been approved by the FDA for a variety of cancers including lung, liver, and breast. It is still in clinical trials for mesothelioma but has been indicated as a useful option for long-term survival.
The effectiveness of paclitaxel is still being studied by doctors. While it has had success with other cancers like lung and ovarian cancer, it has only had middling results with mesothelioma.
New clinical trials will assess paclitaxel’s efficacy when it is combined with other drugs like cisplatin or carboplatin.
When it comes to intraoperative chemotherapy, there are really two options: the aforementioned hyperthermic (heated) intraperitoneal chemotherapy (HIPEC) for peritoneal mesothelioma and hyperthermic intrathoracic chemotherapy (HITHOC) for pleural mesothelioma.
Both procedures inject chemotherapy drugs to tumor sites during open surgery. HIPEC is usually used during cytoreductive surgery (which eliminates tumors throughout the abdomen) and peritonectomy (which removes the abdominal cavity lining). HITHOC is usually performed during a pleurectomy and decortication (which removes the lung lining and any nearby tumors).
As mentioned above, HIPEC has improved prognoses drastically for many patients, with a 5-year survival rate above 50%. The procedure takes place after the surgical removal of tumors in the abdomen, and it attacks any remaining cancerous cells in the area. The chemotherapy solution (usually just a saline solution at first) can be heated up to as high as 109 degrees Fahrenheit. Cancer cells cannot survive temperatures above 104 degrees, but healthy cells can survive at temperatures of up to 111 degrees.
Once the solution has been heated up to the proper temperature in a perfusion system, doctors insert high quantities of chemotherapy drugs and send the entire solution to the affected area via an inflow catheter. The chemotherapy drugs intermingle with a solution and begin to fill the abdominal cavity. An outflow catheter also continuously removes the solution back into the perfusion system, effectively recycling it.
When the procedure is finished, doctors will wash out the abdomen with a strict saline solution. The surgery and HIPEC together can take as long as 18 hours to complete, but occasionally the whole procedure can be completed in six hours.
The HITHOC procedure is similar except that it occurs in the chest cavity rather than the abdominal cavity. HITHOC is also associated with higher median survival times. The average survival time for those who underwent HITHOC was about 35 months compared to only 22 months for those who did not undergo the procedure.
Common chemotherapy drugs used during these intraoperative procedures include:
Not everyone is a good candidate for HIPEC or HITHOC procedures. This is largely due to the fact that mesothelioma is usually diagnosed in its later stages when a procedure like this would prove to be unsuccessful. Patients who are diagnosed in the early stages and whose disease has had limited metastasis are the best candidates.
The heated chemotherapy procedures do not cause many side effects. Regular systemic chemotherapy usually sends drugs through the entire body, which can kill both healthy and cancerous cells and cause various side effects.
Intraoperative procedures, on the other hand, are more direct and are exposed to healthy cells in a much more limited area for a shorter amount of time. Thus, the side effects aren’t as bad. Most of the recovery time is associated with the surgery, and it can include a hospital stay of up to two weeks.
Side Effects of Mesothelioma Chemotherapy Drugs
The unfortunate issue with chemotherapy drugs is that they often cause a cavalcade of side effects. As mentioned above, chemotherapy drugs do not differentiate between healthy cells and cancer cells when they attack them. They often just aim for cells that grow rapidly.
This can lead to numerous symptoms including:
- Hair loss
- Sores in the mouth
- Low blood cell counts
Another common symptom associated with chemotherapy is colloquially referred to as “chemo brain.” The term refers to cognitive impairment that can result in issues with concentration, memory, multitasking, and overall cognitive function. Many patients report that they feel mentally languid and may even misplace things or forget names or faces that they would have otherwise remembered.
Chemo brain can be a temporary condition lasting only as long as chemotherapy treatments. For others, it can last for years after chemotherapy treatments have ended. In rare cases, the cognitive impairment associated with chemo brain remains permanently. Despite this, chemotherapy is one of the best methods for saving people’s lives, and it’s probable that most patients would happily choose to live with chemo brain than the alternative.
As research progresses, mesothelioma chemotherapy treatments are only going to get better. Other treatment options may also provide patients with better health without the associated side effects. In any event, the race toward a cure for mesothelioma will undoubtedly begin producing results in the near future.