In February 2004, the U.S.Food and Drug Administration (FDA) approved pemetrexed for treatment of malignant pleural mesothelioma, a type of tumor of themesothelium, the thin layer of tissue that covers many of the internal organs, in combination withcisplatin[8] for patients whose disease is either unresectable or who are not otherwise candidates for curative surgery.[9] In September 2008, the FDA granted approval as a first-line treatment, in combination with cisplatin, against locally advanced and metastaticnon-small cell lung cancer (NSCLC) in patients with non-squamous histology.[10][11][2]
Pemetrexed is also recommended in combination withcarboplatin andpembrolizumab for the first-line treatment of advanced non-small cell lung cancer.[12][13] 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.[14]
Patients are recommended to takefolic acid andvitamin B12 supplement even if levels are normal when they are on pemetrexed therapy.[15][2] (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 aglucocorticoid (e.g.dexamethasone) on the day prior, day of, and day after pemetrexed infusion to avoid skin rashes.[2]
The administration of cisplatin andvitamin B12 concomitantly does not modify thepharmacokinetics 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[16]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.
A Phase III study showed benefits of maintenance use of pemetrexed for non-squamous NSCLC.[21] Activity has been shown in malignant peritoneal mesothelioma.[22]
^Rossi A, Ricciardi S, Maione P, de Marinis F, Gridelli C (November 2009). "Pemetrexed in the treatment of advanced non-squamous lung cancer".Lung Cancer.66 (2):141–149.doi:10.1016/j.lungcan.2009.06.006.PMID19577816.
^Ettinger DS, et al."Non-small Cell Lung Cancer V.1.2007"(PDF).NCCN Clinical Practice Guidelines in Oncology. National Comprehensive Cancer Network (NCCN). Archived fromthe original(PDF) on 23 March 2007.
^Daoudi, Redoane (26 September 2024). "Characterization and implication of the Orai3 channel and ABC type transporters in the phenomenon of chemoresistance to cisplatin and pemetrexed in lung cancer".bioRxiv10.1101/2024.09.22.613742.
^Carteni G, Manegold C, Garcia GM, Siena S, Zielinski CC, Amadori D, et al. (May 2009). "Malignant peritoneal mesothelioma-Results from the International Expanded Access Program using pemetrexed alone or in combination with a platinum agent".Lung Cancer.64 (2):211–218.doi:10.1016/j.lungcan.2008.08.013.PMID19042053.
N
Y (what is this?) (verify)
