Pemetrexed, sold under the brand name Alimta among others, is a

chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

medication for the treatment of

pleural The pleural cavity, or pleural space (or sometimes intrapleural space), is the potential space between the pulmonary pleurae, pleurae of the pleural sac that surrounds each lung. A small amount of serous fluid, serous pleural fluid is maintained ...

mesothelioma Mesothelioma is a type of cancer that develops from the thin layer of tissue that covers many of the internal organs (known as the mesothelium). The area most commonly affected is the lining of the lungs and chest wall. Less commonly the lini ...

and

non-small cell lung cancer Non-small-cell lung cancer (NSCLC), or non-small-cell lung carcinoma, is any type of epithelial lung cancer other than small-cell lung cancer (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitiv ...

(NSCLC). It is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

Medical use

In February 2004, the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) approved pemetrexed for treatment of malignant pleural mesothelioma, a type of tumor of the

mesothelium The mesothelium is a membrane composed of simple squamous epithelium, simple squamous epithelial cells of mesodermal origin, which forms the lining of several body cavities: the pleura (pleural cavity around the lungs), peritoneum (abdominopelvic ...

, the thin layer of tissue that covers many of the internal organs, in combination with

cisplatin Cisplatin is a chemical compound with chemical formula, formula ''cis''-. It is a coordination complex of platinum that is used as a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, c ...

for patients whose disease is either unresectable or who are not otherwise candidates for curative surgery. In September 2008, the FDA granted approval as a first-line treatment, in combination with cisplatin, against locally advanced and metastatic

(NSCLC) in patients with non-squamous histology.

Carboplatin

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.

Supplementation

Patients are recommended to take

folic acid Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...

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 Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebra ...

(e.g.

dexamethasone Dexamethasone is a fluorinated glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive pulmonary disease (COPD), croup, brain swelling, eye pain following eye su ...

) on the day prior, day of, and day after pemetrexed infusion to avoid skin rashes.

Drug interaction

The administration of cisplatin and vitamin B₁₂ concomitantly does not modify the

pharmacokinetics Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to describing how the body affects a specific su ...

of the pemetrexed. It was recently shown that pemetrexed may play a role in cisplatin resistance in lung cancer by increasing the expression of Orai3 calcium channels as well as the expression of certain ABC transporters like MDR1 and MRP-5 responsible for cisplatin efflux and therefore a reduction of the effect of cisplatin As current therapies are based on the co-administration of pemetrexed and cisplatin, there may be interactions between pemetrexed and cisplatin, including a reduction in the therapeutic effects of cisplatin caused by pemetrexed.

Mechanism of action

Pemetrexed is chemically similar to

and is in the class of chemotherapy drugs called folate antimetabolites. It works by inhibiting three enzymes used in

purine Purine is a heterocyclic aromatic organic compound that consists of two rings (pyrimidine and imidazole) fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which include substituted puri ...

and

pyrimidine Pyrimidine (; ) is an aromatic, heterocyclic, organic compound similar to pyridine (). One of the three diazines (six-membered heterocyclics with two nitrogen atoms in the ring), it has nitrogen atoms at positions 1 and 3 in the ring. The oth ...

synthesis—

thymidylate synthase Thymidylate synthase (TS) () is an enzyme that catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP). Thymidine is one of the nucleotides in DNA. With inhibition of TS, an imbalance of deoxynucleot ...

(TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). By inhibiting the formation of precursor purine and pyrimidine

nucleotide Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...

s, pemetrexed prevents the formation of

DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...

and

RNA Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...

, which are required for the growth and survival of both normal cells and cancer cells.

Society and culture

Economics

In the United States, , each vial of the medication costs between and .

Brand names

In February 2020, Pemfexy was approved for use in the United States.

Research

A Phase III study showed benefits of maintenance use of pemetrexed for non-squamous NSCLC. Activity has been shown in malignant peritoneal mesothelioma.

References

External links

* * {{Portal bar , Medicine Mammalian dihydrofolate reductase inhibitors Drugs developed by Eli Lilly and Company Pyrrolopyrimidines Benzamides Antifolates Thymidylate synthase inhibitors Purines