|Trade names||Alimta, Pemfexy, Ciambra, others|
|Main uses||Mesothelioma, non-small cell lung cancer (NSCLC)|
|Side effects||Fever, infection, inflammation of the mouth, rash, nausea, tiredness, shortness of breath, chest pain|
|Typical dose||500 mg/m2|
|Elimination half-life||3.5 hours|
|Chemical and physical data|
|Molar mass||427.417 g·mol−1|
|3D model (JSmol)|
|(what is this?)|
Pemetrexed, sold under the brand name Alimta among others, is a medication used to treat mesothelioma and non-small cell lung cancer (NSCLC). It is used for mesothelioma which involves the pleura and cannot be removed by surgery. It is given by gradual injection into a vein.
Common side effects include fever, infection, inflammation of the mouth, rash, nausea, tiredness, shortness of breath, and chest pain. Other side effects may include bone marrow suppression. Use in pregnancy may harm the baby. It works by blocking the creation of DNA and RNA by inhibiting thymidylate transferase.
Pemetrexed was approved for medical use in the United States and Europe in 2004. It is available as a generic medication. In the United Kingdom 500 mg costs the NHS about £450 as of 2021. This amount in the United States is about 3,700 USD.
It is used for the treatment of malignant pleural mesothelioma, a type of tumor of the mesothelium, the thin layer of tissue that covers many of the internal organs, in combination with cisplatin in people whose disease is either unresectable or who are not otherwise candidates for curative surgery. It is a first-line treatment, in combination with cisplatin, against locally advanced and metastatic non-small cell lung cancer (NSCLC) in people with non-squamous histology.
Pemetrexed is also recommended in combination with carboplatin and pembrolizumab for the first-line treatment of advanced non-small cell lung cancer. However, the relative efficacy or toxicity of pemetrexed-cisplatin versus pemetrexed-carboplatin has not been established beyond what is generally thought about cisplatin or carboplatin doublet drug therapy.
Patients are recommended to take folic acid and vitamin B12 supplement even if levels are normal when they are on pemetrexed therapy. (In clinical trials for mesothelioma, folic acid and B12 supplementation reduced the frequency of adverse events.) It is also recommended for patients to be on a glucocorticoid (e.g. dexamethasone) on the day prior, day of, and day after pemetrexed infusion to avoid skin rashes.
It is given at a dose of 500 mg/m2 every three weeks.
Pemetrexed, whether used alone or in combination with cisplatin, has these side effects:
- Low blood cell counts, as measured by a complete blood count. This is a dose-limiting toxicity.
- Mental fatigue and sleepiness. Fatigue can be reduced through an off-label prescription of modafinil.
- Nausea and vomiting. Pemetrexed's emetogenic effects are managed with prophylactic antiemetics.
- Oral mucositis (mouth, throat, or lip sores). Oral ulcers can be mitigated by proper oral hygiene, including rinsing of the mouth with salt water following consumption of food or drink.
- Loss of appetite
- Skin rash. Physician-prescribed glucocorticoids administered on the day prior, day of, and day after infusion typically avoid skin rashes.
Mechanism of action
Pemetrexed is chemically similar to folic acid and is in the class of chemotherapy drugs called folate antimetabolites. It works by inhibiting three enzymes used in purine and pyrimidine synthesis—thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). By inhibiting the formation of precursor purine and pyrimidine nucleotides, pemetrexed prevents the formation of DNA and RNA, which are required for the growth and survival of both normal cells and cancer cells.
The molecular structure of pemetrexed was developed by Edward C. Taylor at Princeton University and clinically developed by Indianapolis-based drug maker, Eli Lilly and Company in 2004.
Society and culture
In addition to the brand name Alimta, this drug is also marketed in India by Abbott Healthcare as Pleumet and by Cadila Healthcare as Pemecad. In February 2020, Pemfexy was approved for use in the United States.
A Phase III study showed benefits of maintenance use of pemetrexed for non-squamous NSCLC. Activity has been shown in malignant peritoneal mesothelioma. Trials are currently[when?] testing it against esophageal cancer, chordoma and other cancers.
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