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Alimta (Pemetrexed) and Mesothelioma

Alimta®

Alimta, also known generically as pemetrexed, is a brand-name chemotherapy drug developed and marketed by Eli Lilly and Company for cancer treatment, including for patients with malignant pleural mesothelioma and nonsquamous non-small cell lung cancer (NSCLC).

In 2004, Alimta received Food and Drug Administration (FDA) approval as a combination therapy for pleural mesothelioma patients. It is the first and only FDA approved chemotherapy drug for mesothelioma. Typically, Alimta is combined with cisplatin, a platinum-based chemotherapy drug, to treat mesothelioma as either an initial treatment or second-line treatment after surgery. In some cases, it can be combined with other platinum-based chemotherapy drugs or bevacizumab, another targeted therapy that combats tumor growth.

How Alimta Is Used to Treat Mesothelioma

According to the National Comprehensive Cancer Network (NCCN), pemetrexed can be delivered as a single agent treatment or in combination with other chemo drugs as a first-line treatment for all types of mesothelioma. For patients who are not candidates for surgery, pemetrexed is often the recommended first-line therapy. As part of a multimodal treatment plan, the American Society of Clinical Oncology (ASCO) notes that pemetrexed can be given either before or after surgery, typically ranging between 4 – 6 treatment cycles. If patients respond favorably to the treatment, they may be allowed to take a break from continued chemotherapy.

Pemetrexed is given to patients through an IV and takes about 10 minutes to complete. The process is performed every three weeks for several cycles, depending on the patient’s individual case. Mesothelioma patients may be able to stay on the drug as part of a maintenance treatment plan if the cancer has remained stable or decreased in size.

Depending on how the body responds to the treatments, a patient’s healthcare team can perform blood tests to determine whether or not the dosage needs to change or if treatment needs to be slowed or stopped altogether. Factors that could alter the treatment schedule include a patient’s overall health, cancer progression, cell type and other prior or future treatments.

Pemetrexed is also supplemented with folic acid, taken orally, and Vitamin B12 injections. This is meant to reduce the risk of a patient developing side effects associated with their chemotherapy regimen.

Possible Side Effects of Alimta

For patients diagnosed with malignant mesothelioma, treatments involving the use of Alimta have proven effective at killing cancer cells. However, patients may face a number of side effects, which can differ based on how the patient reacts to the treatment and whether or not pemetrexed is given alone or combined with other therapies. By itself, Alimta may cause side effects like fatigue, loss of appetite and nausea. For patients treated with Alimta in combination with cisplatin, more side effects may arise.

Side Effects of Alimta and Cisplatin
  • Low platelet count
  • Low red blood cell count
  • Low white blood cell count
  • Mouth sores
  • Vomiting

Like many other chemotherapy drugs, there is also a risk of the patient sustaining hair loss or thinning, though it’s low for patients taking Alimta combined with cisplatin. When Alimta is combined with carboplatin and pembrolizumab, additional side effects are possible, including headaches, skin rashes or a sore throat. Male patients may also develop fertility issues, though it’s unknown whether or not the issue is permanent.

Pemetrexed has also been linked to several serious side effects, ranging from painful skin reactions and low blood cell counts to kidney damage, lung issues and radiation recall. Radiation recall occurs when the body has been treated with radiation prior to receiving Alimta and generally results in swelling or blistering where the radiation was given.

Patients should also be sure to discuss any other medications and supplements they are taking with their doctors, as it could cause adverse reactions with pemetrexed. According to a 2017 study, researchers noticed that blood problems could develop in patients taking both nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and pemetrexed with carboplatin, especially for those with renal insufficiencies.

The manufacturers of Alimta have stated that over-the-counter medications like aspirin or ibuprofen may be given in low doses. Higher doses of these common medications are not recommended because there isn’t enough information about their interactions with pemetrexed.

Studies Associated with Alimta

In 2003, prior to receiving FDA approval, a phase 3 clinical study showed that patients who received pemetrexed and cisplatin survived about three months longer than those who received cisplatin alone (12.1 months compared to 9.3 months in the control group). Response rates for patients were also much higher in the group receiving the combination therapy, as opposed to the single agent treatment of cisplatin.

In more recent studies, researchers noted that patients with peritoneal mesothelioma also responded to treatments using pemetrexed as either a single agent or combined with a platinum-based drug like cisplatin. According to one study, patients who received pemetrexed alone had a 1-year survival rate of about 42%, while more than 57% of those who received the drug combined with cisplatin survived for one year. On average, peritoneal mesothelioma patients survive six months to one year.

In 2017, another study of 24 malignant peritoneal mesothelioma patients being treated with pemetrexed and cisplatin resulted in two complete responses and nine partial responses, totaling a 45.8% response rate. Patients also saw a median overall survival of 15.8 months using the drug combination.

Several studies from 2018 also observed the effects of pemetrexed and cisplatin in patients with a certain protein called AXL, which sometimes has an abnormally high expression in patients with mesothelioma. Researchers found that treating patients with an additional AXL inhibitor allowed the chemotherapy drugs to more effectively kill cancer cells. With further study, researchers hope to continue to improve the efficacy of pemetrexed.

Author: Linda Molinari

Editor in Chief, Mesothelioma Cancer Alliance

Linda Molinari

Reviewer: Annette Charlevois

Patient Support Coordinator

Annette Charlevois
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Sources

Boons CC, Van Tulder MW, et al. The Value of Pemetrexed for the Treatment of Malignant Pleural Mesothelioma: A Comprehensive Review. Anticancer Research. September 2013; 33(9):3553-3561.

Budde LS, Hanna NH. Pemetrexed (Alimta): improving outcomes in malignant pleural mesothelioma. Expert Review of Anticancer Therapy. June 2004; 4(3):361-368. doi: 10.1586/14737140.4.3.361

Carteni G, Manegold C, et al. Malignant peritoneal mesothelioma-Results from the International Expanded Access Program using pemetrexed alone or in combination with a platinum agent. Lung Cancer. May 2009; 64(2):211-218. doi: 10.1016/j.lungcan.2008.08.013

Eli Lilly and Company. FDA Expands Lilly's ALIMTA® (pemetrexed) Label to Include Combination with KEYTRUDA® (pembrolizumab) and Carboplatin as First-Line Treatment for Metastatic Nonsquamous Non-Small Cell Lung Cancer, Irrespective of PD-L1 Expression. June 2018.

Eli Lilly and Company. Medical Answers. Updated January 2017.

Eli Lilly and Company. What Is ALIMTA? June 2018.

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Gay CM, Balaji K, et al. Giving AXL the axe: targeting AXL in human malignancy. British Journal of Cancer. January 2017; 116(4):415-423. doi: 10.1038%2Fbjc.2016.428

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Kawazoe H, Yano A, et al. Non-steroidal anti-inflammatory drugs induce severe hematologic toxicities in lung cancer patients receiving pemetrexed plus carboplatin: A retrospective cohort study. PLOS ONE. February 2017; 12(2). doi: 10.1371/journal.pone.0171066

National Comprehensive Cancer Network. Malignant Pleural Mesothelioma. 2016.

Oien DB, Garay T, et al. Cisplatin and Pemetrexed Activate AXL and AXL Inhibitor BGB324 Enhances Mesothelioma Cell Death from Chemotherapy. Frontiers in Pharmacology. January 2018; 8:970. doi: 10.3389%2Ffphar.2017.00970

Schlei Z, Tan W, et al. Safety of Same-Day Vitamin B12 Supplementation in Patients Receiving Pemetrexed for the Treatment of Non–Small-Cell Lung Cancer or Pleural Mesothelioma: A Retrospective Analysis. Clinical Lung Cancer. June 2018. doi: 10.1016/j.cllc.2018.05.017

University of Iowa Healthcare. Dealing with cancer therapy hair loss. Updated October 2016.

University of Michigan Comprehensive Cancer Center. Drugs that Should Be Avoided While Taking Pemetrexed (Alimta®). Updated January 2011.

Vogelzang NJ, Rusthoven JJ, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. Journal of Clinical Oncology. July 2003; 21(14):2636-2644. doi: 10.1200/JCO.2003.11.136

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