Topotecan

from Wikipedia, the free encyclopedia
Structural formula
Structure of topotecan
General
Non-proprietary name Topotecan
other names
  • ( S ) -9-Dimethylaminomethyl-10-hydroxycamptothecin
  • ( S ) -10 - [(Dimethylamino) methyl] -4-ethyl-4,9-dihydroxy-1 H -pyrano [3 ', 4': 6.7] indolizino [1,2- b ] quinoline-3, 14- (4 H , 12 H ) -dione
  • TOPO, TPT, TTC, NSC-609699, SKF-S 104864, SKF 104864
Molecular formula C 23 H 23 N 3 O 5
External identifiers / databases
CAS number
PubChem 60700
DrugBank DB01030
Wikidata Q419953
Drug information
ATC code

L01 XX17

Drug class

Cytostatic

Mechanism of action

Topoisomerase I inhibitors

properties
Molar mass 421.45 g · mol -1
Physical state

firmly

Melting point

213–218 ° C (topotecan hydrochloride )

solubility

1 mg ml −1 in water

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances

Hydrochloride hydrate

08 - Dangerous to health

Caution

H and P phrases H: 341
P: 281
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Topotecan (INN; trade name Hycamtin ® ; manufacturer Novartis ) is a medicinal substance that is produced semi-synthetically as a derivative ( derivative ) of the phytonutrient camptothecin . Camptothecin is an alkaloid and is obtained from the plant Camptotheca acuminata .

Topotecan is a slightly yellowish to greenish powder and is used as a chemotherapeutic agent for the treatment of cancer diseases . Topotecan belongs to the cytostatic group of topoisomerase inhibitors .

Mechanism of action

Topotecan (like camptothecin) is an inhibitor of DNA topoisomerase I. DNA topoisomerase I has the physiological function of breaking down the shear stress of the DNA double strand by causing DNA single strand breaks. Topotecan attaches itself to the complex of topoisomerase I and DNA and prevents the reclosure of the previously made DNA single strand break . According to current knowledge, the cause replication of DNA by the corresponding enzymes such as DNA polymerases in contact with the complex of topotecan, DNA and DNA topoisomerase I has a double-strand break of the DNA and hence discontinuation of DNA replication . Mammalian cells do not have sufficiently efficient DNA repair mechanisms to repair such DNA double-strand breaks.
In terms of the cell cycle , topotecan is only effective in the S phase of the cell cycle ( DNA synthesis ). Dormant cells (healthy and diseased), which do not synthesize DNA and are therefore not in the S-phase of the cell cycle, are not damaged by topotecan.
Related substances with the same mechanism of action are irinotecan and camptothecin . Etoposide (VP16) and teniposide (VM26) are also topoisomerase inhibitors; however, they inhibit DNA topoisomerase II.

Metabolism

Like irinotecan, topotecan is water-soluble. However, unlike irinotecan, topotecan is not a prodrug .

Application areas)

Ovarian cancer, metastatic and refractory to therapy

In the Federal Republic of Germany, topotecan is approved for the treatment of metastatic (spread) ovarian carcinoma (ovarian cancer) if the ovarian carcinoma did not respond or responded only insufficiently to primary (1st line) treatment (literally: failure of primary or subsequent therapy ).

Lung carcinoma, small-cell, therapy-refractory

In the USA, topotecan is approved for the treatment of small cell lung carcinoma ( SCLC ), which have not responded to primary (1st line) treatment and are sensitive to topotecan.
In the Federal Republic of Germany, topotecan is approved for (quote) "Patients with relapsed small cell lung cancer (SCLC) who are not suitable for re-treatment with the treatment regimen used in primary therapy." (Technical information Hycamtin® 1 mg from 01/2006)

Children and young people

Topotecan is currently being tested in clinical studies in children and adolescents.

According to the current state of knowledge, topotecan is not a standard therapy for the aforementioned tumor diseases .

Contraindications

Topotecan must not be given under any circumstances if:

An indication under the strictest risk-benefit assessment is given for:

  • severely impaired kidney function
  • severely impaired liver function (due to liver cirrhosis with serum bilirubin values> 10 mg / dl)
  • moderate bone marrow depression

Topotecan has not been adequately tested in children and is consequently not approved for children and adolescents. The treatment of children with cancer with the use of topotecan in the context of chemotherapy should - if at all - only be carried out in the context of studies .

Side effects

Individual evidence

  1. Entry on topotecan. In: Römpp Online . Georg Thieme Verlag, accessed on October 1, 2014.
  2. ^ Entry on topotecan in the DrugBank of the University of Alberta .
  3. a b Data sheet Topotecan hydrochloride hydrate from Sigma-Aldrich , accessed on April 24, 2011 ( PDF ).

Web links