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Chemotherapy for Malignant Pleural Mesothelioma

Although there is no cure for malignant mesothelioma, many people with the disease can benefit from chemotherapy. Chemotherapy has been shown to improve survival, particularly in epithelioid mesothelioma. Conversely, sarcomatoid and desmoplastic mesothelioma do not usually respond to chemotherapy.

Before starting chemotherapy, your doctor will evaluate your overall health, specifically:

-Any other medical conditions besides mesothelioma

-Your overall health and fitness level

Chemotherapy Drugs Used for Mesothelioma

The preferred chemotherapy for mesothelioma is a combination regimen. Doctors have found that using more than one drug is the most effective way to treat the cancer. Two drugs are often used. These drugs include:

  • Pemetrexed
  • Cisplatin or carboplatin

Although other chemotherapy drugs have been tried in mesothelioma, the cisplatin/carboplatin and pemetrexed regimen has shown the best results. Further, when combined these agents lead to longer survival than with either drug alone. The average survival for a person on cisplatin/pemetrexed is just over 12 months, compared with an average survival of around 9 months on cisplatin alone. Your doctor may discuss with you the option of using either cisplatin or carboplatin: both of these drugs are thought to work similarly well. Further, pemetrexed and raltitrexed are thought to work similarly well, however, raltitrexed is not currently available in the United States.

How Chemotherapy Works

Chemotherapy is designed to kill cancer cells. Specific mesothelioma chemotherapy drugs work in different ways:

  • Pemetrexed: This drug interferes with the body’s use of folate, which is needed for cancer cells to replicate. By blocking chemical reactions in the body involving folate, pemetrexed helps to fight cancer.
  • Cisplatin and carboplatin: These drugs disrupt DNA formation. Because cancer cells multiply very quickly, they need to copy a lot of DNA. Cisplatin and Carboplatin interrupt this process in part by binding up the chemicals that make DNA.

How Long Chemotherapy Lasts

Many cancer treatments are done in cycles. A cycle means that you are given chemotherapy for a certain period of time, and then you take a break so your body can recover before you repeat the treatment. Chemotherapy for mesothelioma is usually done in 21-day cycles. On day one of the cycle, you will get a 10-minute intravenous infusion of pemetrexed, followed by a 2-hour infusion of cisplatin. Then, you have the next 20 days to recover from the chemotherapy before the next cycle. Doctors have different opinions on how many cycles of chemotherapy should be done. However, people who are responding well to chemotherapy often have 6 cycles of this regimen before it is stopped. Although long-term treatment with pemetrexed has been studied, it was not found to benefit survival.

Other Medications to Take During Chemotherapy

Because pemetrexed disrupts your body’s use of folate, you will need to start taking vitamins about a week before the first pemetrexed dose. You should continue taking them through the chemotherapy. Doing so improves not only side effects from chemotherapy, but also response to chemotherapy. In turn, people who take these vitamins while on pemetrexed have a longer survival time. These vitamins are:

  • Folic acid 400 to 1000 mcg by mouth once daily
  • Vitamin B12, or cyanocobalamin, 1000 mcg injected into a muscle once every 9 weeks

Your doctor may give you additional medications to take before chemotherapy starts. These include:

-Dexamethasone: This steroid may be prescribed for you to take before taking pemetrexed and cisplatin or carboplatin. A typical dose is 4 mg twice daily for three days, starting the day before treatment. Taking this steroid reduces the risk of skin reactions from pemetrexed and helps to lessen nausea and vomiting from cisplatin and carboplatin.

-Anti-emetic agents: Pemetrexed on its own is not very likely to cause nausea and vomiting: only about 10 to 30% of people taking pemetrexed will have this side effect. However, cisplatin and carboplatin are much more likely to cause nausea and vomiting. Cisplatin, in particular, causes this side effect in 90% of people who take the medication. Carboplatin causes nausea and vomiting in anywhere from 30 to 90% of people who take the medication. For this reason, your doctor is very likely to prescribe a multi-drug regimen to control nausea and vomiting, especially if you are taking cisplatin or carboplatin.

What to Expect from Chemotherapy                 

The chemotherapy drugs for mesothelioma are generally given intravenously, or IV. When pemetrexed and cisplatin or carboplatin are used together, pemetrexed is given first. The pemetrexed infusion takes about 10 minutes. Carboplatin takes at least 15 minutes to infuse, but may take up to 1 hour. Cisplatin takes longer to infuse, anywhere from 30 minutes to 4 hours.

Your doctor and nurse will make sure you are properly hydrated both before and after taking cisplatin. Because it often causes vomiting, the drug would otherwise cause dehydration.

Because chemotherapy drugs are designed to be toxic to cancer cells, many people experience side effects. The reason for this is that it is difficult for chemotherapy to work on cancer cells without impacting healthy cells in the body too. Common side effects of chemotherapy for mesothelioma include:

  • Nausea and vomiting
  • Diarrhea or constipation
  • Mouth sores
  • Change in taste
  • Appetite loss
  • Hair loss

Your doctor will be able to work with you to relieve many of these side effects of the regimen as you fight mesothelioma.

References:

  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3886874/
  • https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.8517?af=R
  • https://ascopubs.org/doi/10.1200/JCO.2017.74.4789
  • https://www.ons.org/sites/default/files/emetogenicity_tool.pdf
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830568/
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