Temozolomide

Structural formula
General
Non-proprietary name	Temozolomide
other names	4-methyl-5-oxo-2,3,4,6,8-pentazabicyclo [4.3.0] nona-2,7,9-triene-9-carboxamide
Molecular formula	C 6 H 6 N 6 O 2
External identifiers / databases
EC number	630-358-9
ECHA InfoCard	100.158.652
PubChem	5394
DrugBank	DB00853
Wikidata	Q425088
Drug information
ATC code	L01 AX03
Drug class	Cytostatic
properties
Molar mass	194.15 g · mol -1
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
H and P phrases	H: 302-315-319-335-350-360
	P: 201-261-305 + 351 + 338-308 + 313
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Temozolomide (trade names Temodal ^® , Temodar ) is an orally and intravenously administered alkylating cytostatic agent . Temozolomide is used for the simultaneous, adjuvant and palliative therapy of glioblastomas in combination with radiation therapy.

Effect and pharmacokinetics

The alkylating cytostatic effect antineoplastic by the tumor cell , the DNA replication is disturbed.

The substance is a prodrug that is only activated in the body through metabolism. Temozolomide is hydrolytically cleaved spontaneously, so that MTIC is formed (= 5- (3- N -methyltriazen-1-yl) -imidazole-4-carboxamide). MTIC is also very unstable and quickly breaks down into the products AIC (= 5 (4) -aminoimidazole-4 (5) -carboxamide) and methylhydrazine. Methylhydrazine then methylates bases in the DNA. If this base is in a promoter region of a gene, the methylation leads to inactivation of the gene, which is then no longer expressed. In most cases, cell death is brought about in this way. However, some tumor cells have a repair mechanism that makes them resistant to this active ingredient.

The advantage of temozolomide over the older active ingredient dacarbazine (DTIC) is that the activation up to methylhydrazine is completely spontaneous. Dacarbazine, on the other hand, has to be activated enzymatically.

The absorption takes place quickly, the maximum active ingredient concentration is reached after about 20 minutes. The plasma half-life is 1.8 hours.

Temozolomide can cross the blood-brain barrier , making it suitable for use in brain tumors .

indication

Temozolomide is approved for adults with an initially diagnosed glioblastoma multiforme for first-line therapy with adjuvant radiotherapy. There is also approval for use in children and adolescents with recurrent malignant glioma or with malignant glioma that does not respond to standard therapy . It is sometimes used in malignant melanoma . However, there is no official approval for this.

Side effects

Thrombocytopenia and neutropenia can occur as side effects .

Cases of severe liver toxicity have also been reported during treatment with temozolomide. There have been several cases of liver damage including fatal liver failure . The liver can also only be damaged a few weeks after the start of treatment and also after discontinuation. Because of this, there are special recommendations for close monitoring of liver function during treatment with temozolomide.

literature

Stupp, R. et al. : Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. In: N Engl J Med. 352 (10); 987-96; doi : 10.1056 / NEJMoa043330 (free full text). PMID 15758009 .
Temodal hard capsules - Information for professionals

Individual evidence

↑ ^a ^b Data sheet Temozolomide from Sigma-Aldrich , accessed on April 23, 2011 ( PDF ).
↑ FDA data sheet Temodar (PDF) Last revision February 2011 (English).
↑ Middleton MR, Grob JJ, Aaronson N, Fierlbeck G, Tilgen W, Seiter S, Gore M, Aamdal S, Cebon J, Coates A, Dreno B, Henz M, Schadendorf D, Kapp A, Weiss J, Fraass U, Statkevich P, Muller M, Thatcher N: Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol 2000; 18: 158-166.
↑ Chemotherapy for melanoma patients with inoperable metastases. (No longer available online.) Archived from the original on November 7, 2014 ; accessed on November 6, 2014 . Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. @1@ 2
↑ Important information: Occurrence of severe liver toxicity associated with temozolomide .

[sigma-1] Data sheet Temozolomide from Sigma-Aldrich , accessed on April 23, 2011 ( PDF ).

[FDA-Label-2] FDA data sheet Temodar (PDF) Last revision February 2011 (English).

[3] Middleton MR, Grob JJ, Aaronson N, Fierlbeck G, Tilgen W, Seiter S, Gore M, Aamdal S, Cebon J, Coates A, Dreno B, Henz M, Schadendorf D, Kapp A, Weiss J, Fraass U, Statkevich P, Muller M, Thatcher N: Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol 2000; 18: 158-166.

[4] Chemotherapy for melanoma patients with inoperable metastases. (No longer available online.) Archived from the original on November 7, 2014 ; accessed on November 6, 2014 . Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. @1@ 2

[5] Important information: Occurrence of severe liver toxicity associated with temozolomide .