“Pemetrexed”的意思、由来-开放百科全书

Pemetrexed (brand name Alimta) is a chemotherapy drug manufactured and marketed by Eli Lilly and Company. Its indications are the treatment of pleural mesothelioma and non-small cell lung cancer.

Medical use

In February 2004, the Food and Drug Administration approved pemetrexed for 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^[1] for patients whose disease is either unresectable or who are not otherwise candidates for curative surgery.^[2] In September 2008, the FDA granted approval as a first-line treatment, in combination with cisplatin, against locally advanced and metastatic non-small cell lung cancer (NSCLC) in patients with non-squamous histology.^[3]^[4]^[5] A Phase III study showed benefits of maintenance use of pemetrexed for non-squamous NSCLC.^[6] Activity has been shown in malignant peritoneal mesothelioma.^[7] Trials are currently testing it against esophageal and other cancers.

Carboplatin

Pemetrexed is also recommended in combination with carboplatin for the first-line treatment of advanced non-small cell lung cancer.^[8] 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.^[9]

Supplementation

Patients should take folic acid and vitamin B₁₂ supplement even if levels are normal when they are on pemetrexed therapy.^[10]^[11] (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 steroid (e.g., dexamethasone 4 mg twice daily) on the day prior, day of, and day after Pemetrexed infusion to avoid skin rashes.^[12]

Side effects

Pemetrexed, whether used alone or in combination with cisplatin, has these side effects:^[13]

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^[16]^[17] (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.

History

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

Trade names

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.{{Citation needed|date=April 2012}}

Cost

In the United States as of 2015 each vial of medicine costs between {{US$}}2,623 and {{US$}}3,100.^[18]

References

1. ^{{cite journal |author=Manegold C |title=Pemetrexed (Alimta, MTA, multitargeted antifolate, LY231514) for malignant pleural mesothelioma |journal=Semin. Oncol. |volume=30 |issue=4 Suppl 10 |pages=32–6 |date=August 2003 |pmid=12917819 |url=http://linkinghub.elsevier.com/retrieve/pii/S0093775403002835 |doi=10.1016/S0093-7754(03)00283-5}}
2. ^National Cancer Institute: FDA Approval for Pemetrexed Disodium
3. ^{{cite journal |vauthors=Cohen MH, Justice R, Pazdur R |title=Approval summary: pemetrexed in the initial treatment of advanced/metastatic non-small cell lung cancer |journal=Oncologist |volume=14 |issue=9 |pages=930–5 |date=September 2009 |pmid=19737998 |doi=10.1634/theoncologist.2009-0092 |url=http://theoncologist.alphamedpress.org/cgi/pmidlookup?view=long&pmid=19737998}}
4. ^{{cite journal |vauthors=Rossi A, Ricciardi S, Maione P, de Marinis F, Gridelli C |title=Pemetrexed in the treatment of advanced non-squamous lung cancer |journal=Lung Cancer |volume=66 |issue=2 |pages=141–9 |date=November 2009 |pmid=19577816 |doi=10.1016/j.lungcan.2009.06.006 |url=http://linkinghub.elsevier.com/retrieve/pii/S0169-5002(09)00330-4}}
5. ^{{cite web |title = Healthcare Professional Website |work = ALIMTA.com |publisher = Eli Lilly and Company |url = http://www.alimta.com/hcp/index.jsp |accessdate = 1 December 2008 |archive-url = https://web.archive.org/web/20090107041350/http://www.alimta.com/hcp/index.jsp |archive-date = 7 January 2009 |dead-url = yes |df = dmy-all}}
6. ^{{cite web | title = Maintenance pemetrexed (Pem) plus best supportive care (BSC) versus placebo (Plac) plus BSC: A randomized phase III study in advanced non-small cell lung cancer (NSCLC). | publisher = American Society of Clinical Oncology | url = http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=65&abstractID=33019 | accessdate = 22 July 2009}}
7. ^{{cite journal |vauthors=Carteni G, Manegold C, Garcia GM, etal |title=Malignant peritoneal mesothelioma-Results from the International Expanded Access Program using pemetrexed alone or in combination with a platinum agent |journal=Lung Cancer |volume=64 |issue=2 |pages=211–8 |date=May 2009 |pmid=19042053 |doi=10.1016/j.lungcan.2008.08.013 |url=http://linkinghub.elsevier.com/retrieve/pii/S0169-5002(08)00459-5}}
8. ^Ettinger DS et al. NCCN Clinical Practice Guidelines in Oncology: Non-small Cell Lung Cancer V.2.2009 available from www.nccn.org
9. ^{{cite journal |vauthors=Azzoli CG, Kris MG, Pfister DG |title=Cisplatin versus carboplatin for patients with metastatic non-small-cell lung cancer—an old rivalry renewed |journal=J. Natl. Cancer Inst. |volume=99 |issue=11 |pages=828–9 |date=June 2007 |pmid=17551137 |doi=10.1093/jnci/djk222 |url=http://jnci.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=17551137}}
10. ^{{cite journal |vauthors=Hazarika M, White RM, Johnson JR, Pazdur R |title=FDA drug approval summaries: pemetrexed (Alimta) |journal=Oncologist |volume=9 |issue=5 |pages=482–8 |year=2004 |pmid=15477632 |doi=10.1634/theoncologist.9-5-482 |url=http://theoncologist.alphamedpress.org/cgi/pmidlookup?view=long&pmid=15477632}}
11. ^{{cite web | title = Alimta Patient Packet Insert | work = ALIMTA.com | publisher = Eli Lilly and Company | date = 26 September 2008 | url = http://pi.lilly.com/us/alimta-ppi.pdf | format = PDF | accessdate = 1 December 2008}}
12. ^{{cite web | title = Alimta Prescribing Information | work = ALIMTA.com | publisher = Eli Lilly and Company | date = 26 September 2008 | url = http://pi.lilly.com/us/alimta-pi.pdf | format = PDF | accessdate = 1 December 2008}}
13. ^{{cite web |title = Important Safety Information |work = ALIMTA.com |publisher = Eli Lilly and Company |date = 26 September 2008 |url = http://www.alimta.com/pat/safetyInformationPAT.jsp |accessdate = 1 December 2008 |archive-url = https://web.archive.org/web/20081020082649/http://www.alimta.com/pat/safetyInformationPAT.jsp |archive-date = 20 October 2008 |dead-url = yes |df = dmy-all}}
14. ^{{cite journal |author1 = James P. |author2 = Wilmot Cancer Center |title = Scientists Help Breast Cancer Survivor Lift the Fog of "Chemo Brain" |journal = Dialogue |volume = Fall 2007 |issue = |pages = 2–3 |publisher = University of Rochester Medical Center |url = http://www.urmc.rochester.edu/cancer-center/documents/fall07.pdf |accessdate = 1 December 2008}}{{dead link|date=March 2018 |bot=InternetArchiveBot |fix-attempted=yes }}
15. ^{{cite web | title = Oral Complications of Chemotherapy and Head/Neck Radiation | work = Cancer Topics – Coping with Cancer | publisher = National Cancer Institute | url = http://www.cancer.gov/cancertopics/pdq/supportivecare/oralcomplications/Patient/page5 | accessdate = 1 December 2008}}
16. ^{{Cite journal | vauthors = McLeod HL, Cassidy J, Powrie RH, Priest DG, Zorbas MA, Synold TW, Shibata S, Spicer D, Bissett D, Pithavala YK, Collier MA, Paradiso LJ, Roberts JD | title = Pharmacokinetic and Pharmacodynamic Evaluation of the Glycinamide Ribonucleotide Formyltransferase Inhibitor AG2034 | journal = Clinical Cancer Research; Clinical Trials | volume = 6 | pages = 2677–84 | date = July 2000 | url = http://clincancerres.aacrjournals.org/cgi/content/abstract/6/7/2677 | pmid = 10914709 | issue = 7}}
17. ^{{cite book | last1 = Avendano | first1 = Carmen | author2 = Menendez, J. Carlos | title = Medicinal Chemistry of Anticancer Drugs | publisher = Elsevier | date = April 2008 | location = Amsterdam | page = 37 | url = https://books.google.com/books?id=GjhXyqB5iLcC | isbn = 0-444-52824-5}}
18. ^{{cite news|last1=Langreth|first1=Robert|title=Decoding Big Pharma's Secret Drug Pricing Practices|url=https://www.bloomberg.com/graphics/2016-drug-prices/|accessdate=15 July 2016|publisher=Bloomberg|date=June 29, 2016}}

词条	Pemetrexed
释义	Medical use Carboplatin Supplementation Side effects Mechanism of action History Society and culture Trade names Cost References External links {{Use dmy dates\|date=March 2014}}{{Drugbox \| Verifiedfields = changed \| verifiedrevid = 464197624 \| IUPAC_name = (2S)-2-{[4-[2-(2-amino-4-oxo-1,7-dihydro pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]amino} pentanedioic acid \| image = Pemetrexed.svg \| image2 = Pemetrexed ball-and-stick.png \| tradename = Alimta \| Drugs.com = {{drugs.com\|monograph\|alimta}} \| licence_EU = yes \| licence_US = Pemetrexed \| pregnancy_US = D \| legal_UK = POM \| legal_US = Rx-only \| routes_of_administration = Intravenous \| bioavailability = NA \| protein_bound = 81% \| metabolism = Negligible \| elimination_half-life = 3.5 hours \| excretion = Renal \| CAS_number_Ref = {{cascite\|changed\|??}} \| CAS_number = 137281-23-3 \| ATC_prefix = L01 \| ATC_suffix = BA04 \| ATC_supplemental = \| PubChem = 446556 \| DrugBank_Ref = {{drugbankcite\|correct\|drugbank}} \| DrugBank = DB00642 \| ChemSpiderID_Ref = {{chemspidercite\|correct\|chemspider}} \| ChemSpiderID = 393879 \| UNII_Ref = {{fdacite\|correct\|FDA}} \| UNII = 04Q9AIZ7NO \| KEGG_Ref = {{keggcite\|correct\|kegg}} \| KEGG = D07472 \| ChEMBL_Ref = {{ebicite\|correct\|EBI}} \| ChEMBL = 225072 \| C=20 \| H=21 \| N=5 \| O=6 \| molecular_weight = 427.411 g/mol \| smiles = Nc3nc2[nH]cc(CCc1ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc1)c2c(=O)[nH]3 \| StdInChI_Ref = {{stdinchicite\|correct\|chemspider}} \| StdInChI = 1S/C20H21N5O6/c21-20-24-16-15(18(29)25-20)12(9-22-16)6-3-10-1-4-11(5-2-10)17(28)23-13(19(30)31)7-8-14(26)27/h1-2,4-5,9,13H,3,6-8H2,(H,23,28)(H,26,27)(H,30,31)(H4,21,22,24,25,29)/t13-/m0/s1 \| StdInChIKey_Ref = {{stdinchicite\|correct\|chemspider}} \| StdInChIKey = WBXPDJSOTKVWSJ-ZDUSSCGKSA-N }} Pemetrexed (brand name Alimta) is a chemotherapy drug manufactured and marketed by Eli Lilly and Company. Its indications are the treatment of pleural mesothelioma and non-small cell lung cancer. Medical use In February 2004, the Food and Drug Administration approved pemetrexed for 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^[1] for patients whose disease is either unresectable or who are not otherwise candidates for curative surgery.^[2] In September 2008, the FDA granted approval as a first-line treatment, in combination with cisplatin, against locally advanced and metastatic non-small cell lung cancer (NSCLC) in patients with non-squamous histology.^[3]^[4]^[5] A Phase III study showed benefits of maintenance use of pemetrexed for non-squamous NSCLC.^[6] Activity has been shown in malignant peritoneal mesothelioma.^[7] Trials are currently testing it against esophageal and other cancers. Carboplatin Pemetrexed is also recommended in combination with carboplatin for the first-line treatment of advanced non-small cell lung cancer.^[8] 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.^[9] Supplementation Patients should take folic acid and vitamin B₁₂ supplement even if levels are normal when they are on pemetrexed therapy.^[10]^[11] (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 steroid (e.g., dexamethasone 4 mg twice daily) on the day prior, day of, and day after Pemetrexed infusion to avoid skin rashes.^[12] Side effects Pemetrexed, whether used alone or in combination with cisplatin, has these side effects:^[13] 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 Provigil.^[14] Nausea and vomiting. Pemetrexed's emetogenic effects are managed with prophylactic antiemetics. Diarrhea 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.^[15] Loss of appetite Skin rash. Physician-prescribed steroids administered on the day prior, day of, and day after infusion typically avoid skin rashes. Constipation 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^[16]^[17] (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. History 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. It has been researched in the PARAMOUNT trial. Society and culture Trade names 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.{{Citation needed\|date=April 2012}} Cost In the United States as of 2015 each vial of medicine costs between {{US$}}2,623 and {{US$}}3,100.^[18] References 1. ^{{cite journal \|author=Manegold C \|title=Pemetrexed (Alimta, MTA, multitargeted antifolate, LY231514) for malignant pleural mesothelioma \|journal=Semin. Oncol. \|volume=30 \|issue=4 Suppl 10 \|pages=32–6 \|date=August 2003 \|pmid=12917819 \|url=http://linkinghub.elsevier.com/retrieve/pii/S0093775403002835 \|doi=10.1016/S0093-7754(03)00283-5}} 2. ^National Cancer Institute: FDA Approval for Pemetrexed Disodium 3. ^{{cite journal \|vauthors=Cohen MH, Justice R, Pazdur R \|title=Approval summary: pemetrexed in the initial treatment of advanced/metastatic non-small cell lung cancer \|journal=Oncologist \|volume=14 \|issue=9 \|pages=930–5 \|date=September 2009 \|pmid=19737998 \|doi=10.1634/theoncologist.2009-0092 \|url=http://theoncologist.alphamedpress.org/cgi/pmidlookup?view=long&pmid=19737998}} 4. ^{{cite journal \|vauthors=Rossi A, Ricciardi S, Maione P, de Marinis F, Gridelli C \|title=Pemetrexed in the treatment of advanced non-squamous lung cancer \|journal=Lung Cancer \|volume=66 \|issue=2 \|pages=141–9 \|date=November 2009 \|pmid=19577816 \|doi=10.1016/j.lungcan.2009.06.006 \|url=http://linkinghub.elsevier.com/retrieve/pii/S0169-5002(09)00330-4}} 5. ^{{cite web \|title = Healthcare Professional Website \|work = ALIMTA.com \|publisher = Eli Lilly and Company \|url = http://www.alimta.com/hcp/index.jsp \|accessdate = 1 December 2008 \|archive-url = https://web.archive.org/web/20090107041350/http://www.alimta.com/hcp/index.jsp \|archive-date = 7 January 2009 \|dead-url = yes \|df = dmy-all}} 6. ^{{cite web \| title = Maintenance pemetrexed (Pem) plus best supportive care (BSC) versus placebo (Plac) plus BSC: A randomized phase III study in advanced non-small cell lung cancer (NSCLC). \| publisher = American Society of Clinical Oncology \| url = http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=65&abstractID=33019 \| accessdate = 22 July 2009}} 7. ^{{cite journal \|vauthors=Carteni G, Manegold C, Garcia GM, etal \|title=Malignant peritoneal mesothelioma-Results from the International Expanded Access Program using pemetrexed alone or in combination with a platinum agent \|journal=Lung Cancer \|volume=64 \|issue=2 \|pages=211–8 \|date=May 2009 \|pmid=19042053 \|doi=10.1016/j.lungcan.2008.08.013 \|url=http://linkinghub.elsevier.com/retrieve/pii/S0169-5002(08)00459-5}} 8. ^Ettinger DS et al. NCCN Clinical Practice Guidelines in Oncology: Non-small Cell Lung Cancer V.2.2009 available from www.nccn.org 9. ^{{cite journal \|vauthors=Azzoli CG, Kris MG, Pfister DG \|title=Cisplatin versus carboplatin for patients with metastatic non-small-cell lung cancer—an old rivalry renewed \|journal=J. Natl. Cancer Inst. \|volume=99 \|issue=11 \|pages=828–9 \|date=June 2007 \|pmid=17551137 \|doi=10.1093/jnci/djk222 \|url=http://jnci.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=17551137}} 10. ^{{cite journal \|vauthors=Hazarika M, White RM, Johnson JR, Pazdur R \|title=FDA drug approval summaries: pemetrexed (Alimta) \|journal=Oncologist \|volume=9 \|issue=5 \|pages=482–8 \|year=2004 \|pmid=15477632 \|doi=10.1634/theoncologist.9-5-482 \|url=http://theoncologist.alphamedpress.org/cgi/pmidlookup?view=long&pmid=15477632}} 11. ^{{cite web \| title = Alimta Patient Packet Insert \| work = ALIMTA.com \| publisher = Eli Lilly and Company \| date = 26 September 2008 \| url = http://pi.lilly.com/us/alimta-ppi.pdf \| format = PDF \| accessdate = 1 December 2008}} 12. ^{{cite web \| title = Alimta Prescribing Information \| work = ALIMTA.com \| publisher = Eli Lilly and Company \| date = 26 September 2008 \| url = http://pi.lilly.com/us/alimta-pi.pdf \| format = PDF \| accessdate = 1 December 2008}} 13. ^{{cite web \|title = Important Safety Information \|work = ALIMTA.com \|publisher = Eli Lilly and Company \|date = 26 September 2008 \|url = http://www.alimta.com/pat/safetyInformationPAT.jsp \|accessdate = 1 December 2008 \|archive-url = https://web.archive.org/web/20081020082649/http://www.alimta.com/pat/safetyInformationPAT.jsp \|archive-date = 20 October 2008 \|dead-url = yes \|df = dmy-all}} 14. ^{{cite journal \|author1 = James P. \|author2 = Wilmot Cancer Center \|title = Scientists Help Breast Cancer Survivor Lift the Fog of "Chemo Brain" \|journal = Dialogue \|volume = Fall 2007 \|issue = \|pages = 2–3 \|publisher = University of Rochester Medical Center \|url = http://www.urmc.rochester.edu/cancer-center/documents/fall07.pdf \|accessdate = 1 December 2008}}{{dead link\|date=March 2018 \|bot=InternetArchiveBot \|fix-attempted=yes }} 15. ^{{cite web \| title = Oral Complications of Chemotherapy and Head/Neck Radiation \| work = Cancer Topics – Coping with Cancer \| publisher = National Cancer Institute \| url = http://www.cancer.gov/cancertopics/pdq/supportivecare/oralcomplications/Patient/page5 \| accessdate = 1 December 2008}} 16. ^{{Cite journal \| vauthors = McLeod HL, Cassidy J, Powrie RH, Priest DG, Zorbas MA, Synold TW, Shibata S, Spicer D, Bissett D, Pithavala YK, Collier MA, Paradiso LJ, Roberts JD \| title = Pharmacokinetic and Pharmacodynamic Evaluation of the Glycinamide Ribonucleotide Formyltransferase Inhibitor AG2034 \| journal = Clinical Cancer Research; Clinical Trials \| volume = 6 \| pages = 2677–84 \| date = July 2000 \| url = http://clincancerres.aacrjournals.org/cgi/content/abstract/6/7/2677 \| pmid = 10914709 \| issue = 7}} 17. ^{{cite book \| last1 = Avendano \| first1 = Carmen \| author2 = Menendez, J. Carlos \| title = Medicinal Chemistry of Anticancer Drugs \| publisher = Elsevier \| date = April 2008 \| location = Amsterdam \| page = 37 \| url = https://books.google.com/books?id=GjhXyqB5iLcC \| isbn = 0-444-52824-5}} 18. ^{{cite news\|last1=Langreth\|first1=Robert\|title=Decoding Big Pharma's Secret Drug Pricing Practices\|url=https://www.bloomberg.com/graphics/2016-drug-prices/\|accessdate=15 July 2016\|publisher=Bloomberg\|date=June 29, 2016}} External links Alimta website NCI Drug Information Summary on Pemetrexed Disodium {{Chemotherapeutic agents}}{{Purinergics}}{{Eli Lilly and Company}} 6 : Mammalian dihydrofolate reductase inhibitors\|Eli Lilly and Company\|Pyrrolopyrimidines\|Benzamides\|Antifolates\|Thymidylate synthase inhibitors
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