|Systematic (IUPAC) name|
|Pregnancy cat.||D (AU) D (US)|
|Legal status||POM (UK) ℞-only (US)|
|Routes||Intravenous infusion, oral|
|Bioavailability||31.4 % in humans |
|CAS number||119413-54-6 (hydrochloride)|
|Mol. mass||457.9 g/mol|
|(what is this?)|
Topotecan (trade name Hycamtin) is a chemotherapeutic agent that is a topoisomerase inhibitor. It is a water-soluble derivative of camptothecin. It is used in form of the hydrochloride to treat ovarian cancer and lung cancer, as well as other cancer types.
After GlaxoSmithKline received final FDA approval for Hycamtin Capsules on October 15, 2007, topotecan is the first topoisomerase I inhibitor for oral use.
Indications (approved uses)
- Ovarian cancer (FDA May 1996).
- Cervical cancer (FDA June 2006).
- Small cell lung cancer (SCLC) (FDA Oct 2007).
Mode of action
Hycamtin or topotecan is a semi-synthetic derivative of camptothecin. Camptothecin is a natural product extracted from the bark of the tree Camptotheca acuminata. Topoisomerase-I is a nuclear enzyme that relieves torsional strain in DNA by opening single strand breaks. Once topoisomerase-I creates a single strand break, the DNA can rotate in front of the advancing replication fork. Topotecan intercalates between DNA bases. This intercalation disrupts the DNA duplication machinery when it reaches a site where topotecan is intercalated. This disruption prevents DNA replication, and ultimately leads to cell death. Mammalian cells cannot efficiently repair these double strand breaks. This process leads to breaks in the DNA strand resulting in apoptosis.
- Low blood counts
- Susceptibility to infection
Two generic versions have been approved in EU, and in Nov 2010 the US FDA approved a generic version.
- http://www.fda.gov/CDER/Offices/OODP/whatsnew/topotecan.htm FDA
- http://www.drugs.com/newdrugs/gsk-receives-approval-hycamtin-topotecan-capsules-relapsed-small-cell-lung-cancer-671.html Press release
- Pommier, Y., Leo, E., Zhang, H., Marchand, C. 2010. DNA topoisomerases and their poisoning by anticancer and antibacterial drugs. Chem. Biol. 17: 421-433.
- Staker, B.L. et al (2002). "The mechanism of topoisomerase I poisoning by a camptothecin analog". PNAS 99 (24): 15387–15392. doi:10.1073/pnas.242259599.
- "FDA Rubber-Stamps APP Pharma’s Generic Topotecan for Small Cell Lung and Cervical Cancers". 30 Nov 2010.
- DNA Topoisomerases and Cancer, Yves Pommier Editor, Humana Press 2012
- NCI Drug Dictionary Definition of Topotecan
- NCI Drug Information for Patients
- Use for ovarian cancer