Cabazitaxel

Structural formula
General
Surname	Cabazitaxel
other names	(1 S , 2 S , 3 R , 4 S , 7 R , 9 S , 10 S , 12 R , 15 S ) -4- (acetyloxy) -15 - {[(2 R , 3 S ) -3- { [( tert -butoxy) carbonyl] amino} -2-hydroxy-3-phenylpropanoyl] oxy} -1-hydroxy-9,12-dimethoxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo [ 11.3.1.0 3.10 .0 4.7 ] heptadec-13-en-2-ylbenzoate
Molecular formula	C 45 H 57 NO 14
Brief description	white solid
External identifiers / databases
EC number	680-632-7
ECHA InfoCard	100.205.741
PubChem	9854073
ChemSpider	8029779
DrugBank	DB06772
Wikidata	Q412963
Drug information
ATC code	L01 CD04
properties
Molar mass	835.93 g mol −1
Physical state	firmly
solubility	almost insoluble in water; soluble in ethanol;
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
H and P phrases	H: 302-311-315-341-360-362-372
	P: ?
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Cabazitaxel (trade name Jevtana ^® , manufacturer: Sanofi-Aventis ) is a semi-synthetically obtained cytostatic from the group of taxanes for the treatment of advanced prostate cancer after treatment with another chemotherapy; it is an additional line of therapy for castration-resistant cancer. Cabazitaxel is one of the microtubule inhibitors. In the cell division phase, it inhibits the development of the spindle apparatus (mitosis inhibitor; cytotoxic effect).

synthesis

Cabazitaxel is produced semi-synthetically from the natural substance 10-deacetylbaccatin III , which is obtained by extraction from yew needles (Taxus sp.).

application areas

Cabazitaxel is used as a second-line therapy after docetaxel for castration-resistant prostate cancer . Cabazitaxel is administered every three weeks at a dose of 25 mg / m ² BSA as a one-hour infusion in combination with 10 mg prednisone daily. The patient must have at least 1500 neutrophil granulocytes per cubic millimeter (µl) of blood, otherwise serious infections can occur.

Side effects

Allergic reactions to cabazitaxel are possible. Other side effects include ( febrile ) neutropenia , thrombocytopenia and diarrhea , as well as abdominal pain , back pain , fatigue and fever.

Early benefit assessment (Section 35a SGB V)

In 2012, the Federal Joint Committee (G-BA) passed a resolution regarding the additional benefit of cabazitaxel on the basis of Section 35a SGB V ( AMNOG ) ( early benefit assessment ). Cabazitaxel was compared with Best Supportive Care for patients with hormone-refractory metastatic prostate cancer who progressed during or after docetaxel-containing chemotherapy and for whom re-treatment with docetaxel is no longer an option . For patients who have progressed after chemotherapy containing docetaxel but are still eligible for adequate chemotherapy containing docetaxel, the appropriate comparator therapy was docetaxel in combination with prednisone or prednisolone. According to the G-BA decision, there is an indication of a minor additional benefit if another docetaxel therapy is not an option; an added benefit has not been proven for the other patients.

literature

Sartor AO, Cabazitaxel or mitoxantrone with prednisone in patients with metatstatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel: Final results of a multinational phase III trial (TROPIC) . ASCO 2010
Information from the Drugs Commission of the German Medical Association (AkdÄ) for doctors about newly approved drugs / newly approved indications in the European Union (EU).
Matthew D. Galsky, Argyris Dritselis, Peter Kirkpatrick, William K. Oh: Cabazitaxel . In: Nature Reviews Drug Discovery . tape 9 , no. 9 , 2010, p. 677-678 , doi : 10.1038 / nrd3254 .

Web links

Individual evidence

↑ ^a ^b ^c Medkoo: Cabazitaxel .
↑ ^a ^b Entry on Cabazitaxel in the DrugBank of the University of Alberta , accessed February 6, 2017.
↑ Template: CL Inventory / not harmonized There is not yet a harmonized classification for this substance . A labeling of 7,10-dimethyl-docetaxel in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on February 6, 2017, is reproduced from a self-classification by the distributor .
↑ Michel Bolla, Hendrik van Poppel (Ed.): Management of Prostate Cancer: A Multidisciplinary Approach . 2nd Edition. Springer, Cham 2017, ISBN 978-3-319-42769-0 , pp. 334 ( limited preview in Google Book search).
↑ Prostate Cancer: New Mitosis Inhibitor Approved in the US , Pharmazeutische Zeitung , June 22, 2010.
↑ Johann Sebastian de Bono, Stephane Oudard, Mustafa Ozguroglu, Steinbjørn Hansen, Jean-Pascal Machiels, Ivo Kocak, Gwenaëlle Gravis, Istvan Bodrogi, Mary J Mackenzie, Liji Shen, Martin Roessner, Sunil Gupta, A Oliver Sartor: Prednisone plus cabazitel mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomized open-label trial . In: The Lancet . tape 376 , no. 9747 , 2010, p. 1147-1154 , doi : 10.1016 / S0140-6736 (10) 61389-X .
↑ Dt. Abstract by: JS de Bono et al., Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomized open-label trial , The Lancet, October 2, 2010.
↑ Castration-Resistant Prostate Cancer: Overcoming the Therapy Gap with a New Taxane , 46th ASCO Annual Conference Report.
↑ A11-24 Cabazitaxel - Benefit assessment according to Section 35a SGB V (dossier assessment); Accessed March 26, 2020.
↑ Benefit assessment procedure for the active substance cabazitaxel (prostate carcinoma, docetaxel pretreatment, combination with prednisone or prednisolone); Accessed March 26, 2020.
↑ Jevtana ^® (Cabazitaxel) (PDF; 122 kB) New Medicines Information from the Medicines Commission of the German Medical Association (AkdÄ).

[medkoo-1] Medkoo: Cabazitaxel .

[drugbank-2] Entry on Cabazitaxel in the DrugBank of the University of Alberta , accessed February 6, 2017.

[ECHA-3] Template: CL Inventory / not harmonized There is not yet a harmonized classification for this substance . A labeling of 7,10-dimethyl-docetaxel in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on February 6, 2017, is reproduced from a self-classification by the distributor .

[4] Michel Bolla, Hendrik van Poppel (Ed.): Management of Prostate Cancer: A Multidisciplinary Approach . 2nd Edition. Springer, Cham 2017, ISBN 978-3-319-42769-0 , pp. 334 ( limited preview in Google Book search).

[5] Prostate Cancer: New Mitosis Inhibitor Approved in the US , Pharmazeutische Zeitung , June 22, 2010.

[6] Johann Sebastian de Bono, Stephane Oudard, Mustafa Ozguroglu, Steinbjørn Hansen, Jean-Pascal Machiels, Ivo Kocak, Gwenaëlle Gravis, Istvan Bodrogi, Mary J Mackenzie, Liji Shen, Martin Roessner, Sunil Gupta, A Oliver Sartor: Prednisone plus cabazitel mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomized open-label trial . In: The Lancet . tape 376 , no. 9747 , 2010, p. 1147-1154 , doi : 10.1016 / S0140-6736 (10) 61389-X .

[7] Dt. Abstract by: JS de Bono et al., Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomized open-label trial , The Lancet, October 2, 2010.

[8] Castration-Resistant Prostate Cancer: Overcoming the Therapy Gap with a New Taxane , 46th ASCO Annual Conference Report.

[9] A11-24 Cabazitaxel - Benefit assessment according to Section 35a SGB V (dossier assessment); Accessed March 26, 2020.

[10] Benefit assessment procedure for the active substance cabazitaxel (prostate carcinoma, docetaxel pretreatment, combination with prednisone or prednisolone); Accessed March 26, 2020.

[11] Jevtana ^® (Cabazitaxel) (PDF; 122 kB) New Medicines Information from the Medicines Commission of the German Medical Association (AkdÄ).