Pemetrexed
From Wikipedia, the free encyclopedia
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| Systematic (IUPAC) name | |
|---|---|
| 2-[4-[2-(4-amino-2-oxo-3,5,7-triazabicyclo[4.3.0] nona-3,8,10-trien-9-yl)ethyl] benzoyl] aminopentanedioic acid | |
| Identifiers | |
| CAS number | 137281-23-3 |
| ATC code | L01BA04 |
| PubChem | 60843 |
| DrugBank | APRD00573 |
| Chemical data | |
| Formula | C20H21N5O6 |
| Mol. mass | 427.411 g/mol |
| Pharmacokinetic data | |
| Bioavailability | NA |
| Protein binding | 81% |
| Metabolism | Negligible |
| Half life | 3.5 hours |
| Excretion | Renal |
| Therapeutic considerations | |
| Licence data | |
| Pregnancy cat. |
D(US) |
| Legal status | |
| Routes | Intravenous |
Pemetrexed (brand name Alimta) is a chemotherapy drug manufactured and marketed by Eli Lilly and Company. Its indications are the treatment of pleural mesothelioma as well as non-small cell lung cancer.
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[edit] 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.
[edit] 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[1][2] (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.
[edit] Clinical use
In February 2004, the Food and Drug Administration approved pemetrexed for treatment of malignant pleural mesothelioma, a type of tumor of the lining of the lung, in combination with cisplatin. In September 2008, the FDA granted approval as a first-line treatment, in combination with cisplatin, against of locally-advanced and metastatic non-small cell lung cancer, or NSCLC, in patients with non-squamous histology[3]. A Phase III study showed benefits of maintenance use of pemetrexed for non-squamous NSCLC[4]. Trials are currently testing it against esophagus and other cancers.
[edit] Carboplatin
Pemetrexed is also recommended in combination with carboplatin for the first-line treatment of advanced non-small cell lung cancer[5]. 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[6]
[edit] Supplementation
Patients are required to be on folic acid and vitamin B12 supplementation when they are on pemetrexed therapy[7]. (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 4mg twice daily) on the day prior, day of, and day after Pemetrexed infusion to avoid skin rashes[8].
[edit] Side effects
Pemetrexed, whether used alone or in combination with cisplatin, has these side effects[9]:
- Low blood cell counts, as measured by a Complete Blood Count. This is a dose-limiting toxicity.
- Mental fatigue and Sleepiness. Fatigure can be reduced through an Off-label prescription of Provigil[10].
- 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[11].
- Loss of appetite
- Skin Rash. Physician-prescribed steroids administered on the day prior, day of, and day after infusion typically avoid skin rashes.
- Constipation
[edit] External links
- Alimta / Pemetrexed Virtual Cancer Centre
- Alimta website
- NCI Drug Information Summary on Pemetrexed Disodium
[edit] References
- ^ McLeod, Howard L.; James Cassidy, Robert H. Powrie, David G. Priest, Mark A. Zorbas, Timothy W. Synold, Stephen Shibata, Darcy Spicer, Donald Bissett, Yazdi K. Pithavala, Mary A. Collier, Linda J. Paradiso, John D. Roberts (Jul-2000), "Pharmacokinetic and Pharmacodynamic Evaluation of the Glycinamide Ribonucleotide Formyltransferase Inhibitor AG2034", Clinical Cancer Research (American Association for Cancer Research) 6: 2677-2684, http://clincancerres.aacrjournals.org/cgi/content/abstract/6/7/2677, retrieved 2-Dec-2008
- ^ Avendano, Carmen; Menendez, J. Carlos (16-Apr-2008). Medicinal Chemistry of Anticancer Drugs. Amsterdam: Elsevier. p. 37. ISBN 0-4445-2824-5. http://books.google.com/books?id=GjhXyqB5iLcC.
- ^ "Healthcare Professional Website" (HTML). ALIMTA.com. Eli Lilly and Company. http://www.alimta.com/hcp/index.jsp. Retrieved 1-Dec-2008.
- ^ "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)." (HTML). American Society of Clinical Oncology. http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=65&abstractID=33019. Retrieved 22-Jul-2009.
- ^ Ettinger DS et al. NCCN Clinical Practice Guidelines in Oncology: Non-small Cell Lung Cancer V.2.2009 available from www.nccn.org
- ^ Azzoli CG, Kris MG, Pfister DG. (2007) Cisplatin versus carboplatin for patients with metastatic non-small-cell lung cancer- An old rivalry renewed. JNCI v99(11) pg. 828-829
- ^ "Alimta Patient Packet Insert" (PDF). ALIMTA.com. Eli Lilly and Company. 26-Sep-2008. http://pi.lilly.com/us/alimta-ppi.pdf. Retrieved 1-Dec-2008.
- ^ "Alimta Prescribing Information" (PDF). ALIMTA.com. Eli Lilly and Company. 26-Sep-2008. http://pi.lilly.com/us/alimta-pi.pdf. Retrieved 1-Dec-2008.
- ^ "Important Safety Information" (HTML). ALIMTA.com. Eli Lilly and Company. 26-Sep-2008. http://www.alimta.com/pat/safetyInformationPAT.jsp. Retrieved 1-Dec-2008.
- ^ James P. Wilmot Cancer Center. "Scientists Help Breast Cancer Survivor Lift the Fog of “Chemo Brain”". Dialogue (University of Rochester Medical Center) Fall 2007: 2-3. http://www.urmc.rochester.edu/cancer-center/documents/fall07.pdf. Retrieved 1-Dec-2008.
- ^ "Oral Complications of Chemotherapy and Head/Neck Radiation" (HTML). Cancer Topics - Coping with Cancer. National Cancer Institute. http://www.cancer.gov/cancertopics/pdq/supportivecare/oralcomplications/Patient/page5. Retrieved 1-Dec-2008.
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