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The addition of bevacizumab to malignant pleural mesothelioma chemotherapy regimens

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Over the past several years, an increasing number of studies have looked at using the drug bevacizumab in malignant pleural mesothelioma. As a result, the National Comprehensive Cancer Network, or NCCN, considers bevacizumab to be a first-line treatment option for mesothelioma in combination with other agents. However, bevacizumab has not yet been approved by the FDA for mesothelioma treatment. For this reason, people may not be aware that doctors consider bevacizumab to be a good treatment option for mesothelioma.

What is bevacizumab?

Bevacizumab, sold under the brand names Avastin, Mvasi and Zirabev, is an anti-cancer drug. It has been approved by the FDA for use in several different cancers including:

-Colorectal cancer

-Glioblastoma

-Lung cancer

-Kidney cancer

-Cervical cancer

-Ovarian cancer

-Fallopian tube cancer

-Peritoneal cancer

Although bevacizumab is not FDA-approved for mesothelioma, it may be used off-label by some doctors to try to slow down the cancer.

How does bevacizumab fight cancer?

Cancers like mesothelioma are deadly because they grow quickly. To do so, the cancer cells need nutrients, oxygen and blood flow. Because blood vessels carry these needed components to the cancer cells, preventing cancer cells from accessing blood vessels can be an important part of cancer therapy. Bevacizumab is an antibody that helps stop tumor blood vessels from growing. The drug does this by stopping a chemical called vascular endothelial growth factor, or VEGF. Under normal circumstances, VEGF encourages blood vessel growth by binding to Flt-1 and KDR receptors on endothelial cells, which line blood vessels in the body. Bevacizumab puts the brakes on this process by binding to VEGF and stopping it from interacting with cells. Therefore, VEGF can no longer bind to the Flt-1 and KDR receptors and coax more blood vessels to grow in the tumor. In this way, bevacizumab helps to stop blood vessels from growing and feeding the cancer. As a result, the cancer may be forced to shrink or grow more slowly.

Bevacizumab in mesothelioma

A combination regimen of anti-cancer drugs is the most effective way to treat mesothelioma. The drugs most often used are:

-Pemetrexed

-Cisplatin or carboplatin

The NCCN considers bevacizumab, in combination with pemetrexed and cisplatin, to be a first-line treatment choice for mesothelioma. After the initial chemotherapy with the three agents is complete, the NCCN recommends continuing bevacizumab.

Multiple studies have looked at the role of bevacizumab in mesothelioma, adding it to the standard therapy of pemetrexed and cisplatin. At this time, no studies have looked at bevacizumab when used with carboplatin.

One study that looked at combining bevacizumab, pemetrexed and cisplatin found that adding bevacizumab increased mesothelioma survival by almost 3 months, from 16.1 months without the drug to 18.8 months with it.

Besides increasing survival, adding bevacizumab to a chemotherapy regimen may also help avoid side effects of pemetrexed and cisplatin therapy like nerve pain. One study showed that bothersome nerve pain took longer to show up (12 months) in people treated with a three-drug regimen of bevacizumab, pemetrexed and cisplatin than in people taking pemetrexed and cisplatin alone (7.5 months). The amount of time that people had pain from cancer was also reduced in the study, which showed that bevacizumab may help improve quality of life for people with mesothelioma.

Studies have also looked at bevacizumab in combination with alternate mesothelioma treatment regimens. One study investigated bevacizumab, cisplatin and the cancer drug gemcitabine. Adding bevacizumab to cisplatin and gemcitabine increased overall mesothelioma survival by almost a month, from 14.7 months without bevacizumab to 15.6 months with the drug. Further, more people had a response to the treatment when bevacizumab was included in the regimen. However, due to the design of this study, researchers were unable to prove that this improvement was due to bevacizumab. It is, therefore, unclear to doctors if bevacizumab helps people taking cisplatin and gemcitabine.

Dosing and administration of bevacizumab in mesothelioma

Although bevacizumab is not FDA-approved for mesothelioma at this time, doctors have studied optimal dosing and duration of treatment.

Bevacizumab is administered intravenously, or IV, like cisplatin and pemetrexed. The dose of bevacizumab depends on the person’s weight. One study showed that bevacizumab, when given at a dose of 15 milligrams per kilogram of body weight, helped fight mesothelioma when it was given during chemotherapy sessions with pemetrexed and cisplatin. After the treatment course with pemetrexed and cisplatin was completed, the study showed that bevacizumab could still fight cancer when given at the same dose once every three weeks. The treatment can be continued as long as the person and their doctor choose to continue it.

Side effects from adding bevacizumab to mesothelioma regimens

In people taking cisplatin and pemetrexed for mesothelioma, the most common side effects when bevacizumab is added are:

-An increased risk of high blood pressure: In one study, nobody taking cisplatin and pemetrexed had a side effect of high blood pressure. However, in people who also took bevacizumab, 23% ended up with high blood pressure after taking the medication.

-A higher risk of blood clots: In the study, 1% of people taking cisplatin and pemetrexed had blood clots. In people who also took bevacizumab, 6% ended up getting a blood clot.

Although few effective treatments for mesothelioma have been approved by the FDA, bevacizumab is a promising option. Working in combination with pemetrexed and cisplatin, it is now a first-line choice to help fight mesothelioma. As more studies are conducted, researchers are hopeful that even more effective treatments will be developed.

References:

  • https://clincancerres.aacrjournals.org/content/early/2019/06/07/1078-0432.CCR-18-2860
  • https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=939b5d1f-9fb2-4499-80ef-0607aa6b114e
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6204415/pdf/tlcr-07-05-574.pdf
  • https://www.nccn.org/about/news/ebulletin/ebulletindetail.aspx?ebulletinid=613
  • https://www.ncbi.nlm.nih.gov/pubmed/26719230
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