Oxaliplatin

from Wikipedia, the free encyclopedia
Structural formula
Structural formula of oxaliplatin
General
Non-proprietary name Oxaliplatin
other names
  • Oxalatoplatin
  • trans - L - (-) - diaminocyclohexanoxalatoplatinum
  • Oxalato [(1 R , 2 R ) -cyclohexanediamine] platinum (II)
  • Pt- (Oxalato) -trans-1-diaminocyclohexane
Molecular formula C 8 H 14 N 2 O 4 Pt
External identifiers / databases
CAS number 61825-94-3
EC number 621-248-1
ECHA InfoCard 100.150.118
PubChem 11947679
DrugBank DB00526
Wikidata Q422327
Drug information
ATC code

L01 XA03

Drug class

Cytostatic

properties
Molar mass 397.28 g mol −1
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
07 - Warning 08 - Dangerous to health

Caution

H and P phrases H: 315-317-319-335-351
P: 261-280-305 + 351 + 338
Toxicological data

14.3 mg kg −1 ( LD 50 ,  rat ,  ip )

As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Oxaliplatin is a cytostatically active drug from the group of platinum derivatives. It is approved in combination with 5-fluorouracil (5-FU) and folinic acid (FS) for the treatment of colorectal cancer ( FOLFOX scheme).

chemistry

Oxaliplatin is an antineoplastic substance and belongs to a new class of platinum complexes in which the platinum ion is complexed with a 1,2-diaminocyclohexane ligand ( DACH ligand for short) and an oxalate ion. Oxaliplatin is a pure enantiomer , the cis - [oxalato ( trans - L -1,2-diaminocyclohexane) platinum].

pharmacology

effectiveness

The effectiveness of the combination therapy of oxaliplatin with 5-fluorouracil / folinic acid (5-FU / FS) has been proven in numerous studies . Oxaliplatin is included in all guidelines for the treatment of colorectal cancer for the respective indication areas with the highest level of recommendation. Current studies indicate that an additional combination with the monoclonal antibody bevacizumab or panitumumab can further improve survival rates significantly.

application

Oxaliplatin is used in combination with 5-fluorouracil and folinic acid and is approved for adults

  • for the adjuvant treatment of stage III colon cancer (Dukes C) after complete removal of the primary tumor,
  • for the treatment of metastatic colorectal cancer.

A common combination is the FOLFOX4 regimen with an oxaliplatin infusion on the first day and subsequent continuous infusion of 5-fluorouracil over two days.

Mechanism of action

Oxaliplatin has the effect that metabolic products formed in the body, similar to cis- or carboplatin, interact with the DNA and form cross-links in and between the DNA strands. The 1,2-diaminocyclohexane ligand (DACH ligand) influences the ability of the cell to tolerate DNA-platinum adducts. The difference in the effect of oxaliplatin and cis- / carboplatin is based on this. The DACH-platinum adducts, which are formed from oxaliplatinum, inhibit DNA synthesis more strongly than the cis-diamino-platinum adducts, which are formed from cis- and carboplatinum.

Side effects

The most common side effects of oxaliplatin in combination with 5-fluorouracil and folinic acid are diarrhea , nausea, vomiting and inflammation of the mucous membranes, changes in the blood count and peripheral sensory neuropathy (s) (neurological abnormalities). The latter is often dose-limiting.

development

  • 1996 - Oxaliplatin approved for second line treatment of metastatic colorectal cancer in France
  • 1998 - Approval extension also for first line therapy
  • 1999 - Approval of oxaliplatin for first line therapy as part of the mutual recognition process in Germany and the other European countries
  • 2002 - FDA approved oxaliplatin for second-line treatment of advanced colorectal cancer in the US
  • 2004 - Approval extensions also for first line therapy in the USA and for the adjuvant treatment of colon cancer in the early stages in Europe

Trade names

Monopreparations

Bendaplatin (D), Croloxat (D), Eloxatin (D, A, CH), Medoxa (D), various generics (D, A)

Individual evidence

  1. ↑ a b Oxaliplatin data sheet from Sigma-Aldrich , accessed on April 16, 2011 ( PDF ).
  2. ↑ Entry on oxaliplatin in the ChemIDplus database of the United States National Library of Medicine (NLM)