DOCETAXEL ANHYDROUS

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C43H53NO14
Molecular Weight	807.8792
Optical Activity	UNSPECIFIED
Defined Stereocenters	11 / 11
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]12[C@H](OC(=O)C3=CC=CC=C3)[C@]4(O)C[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C5=CC=CC=C5)C(C)=C([C@@H](O)C(=O)[C@]1(C)[C@@H](O)C[C@H]6OC[C@@]26OC(C)=O)C4(C)C

InChI

InChIKey=ZDZOTLJHXYCWBA-VCVYQWHSSA-N

InChI=1S/C43H53NO14/c1-22-26(55-37(51)32(48)30(24-15-11-9-12-16-24)44-38(52)58-39(3,4)5)20-43(53)35(56-36(50)25-17-13-10-14-18-25)33-41(8,34(49)31(47)29(22)40(43,6)7)27(46)19-28-42(33,21-54-28)57-23(2)45/h9-18,26-28,30-33,35,46-48,53H,19-21H2,1-8H3,(H,44,52)/t26-,27-,28+,30-,31+,32+,33-,35-,41+,42-,43+/m0/s1

HIDE SMILES / InChI

Molecular Formula	C43H53NO14
Molecular Weight	807.8792
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	10 / 11
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020449s075lbl.pdf
Curator's Comment: description was created based on several sources, including

Docetaxel was protected by patents (U.S. patent and European patent) which were owned by Sanofi-Aventis, and so was available only under the Taxotere brand name internationally. The European patent expired in 2010. Docetaxel is a clinically well-established anti-mitotic chemotherapy medication used for the treatment of patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy. Also used as a single agent in the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of prior platinum-based chemotherapy. It is also used in combination with prednisone, in the treatment of patients with androgen independent (hormone refractory) metastatic prostate cancer. Furthermore, docetaxel has uses in the treatment of gastric adenocarcinoma and head and neck cancer. Docetaxel interferes with the normal function of microtubule growth. Whereas drugs like colchicine cause the depolymerization of microtubules in vivo, docetaxel arrests their function by having the opposite effect; it hyper-stabilizes their structure. This destroys the cell's ability to use its cytoskeleton in a flexible manner. Specifically, docetaxel binds to the β-subunit of tubulin. Tubulin is the "building block" of mictotubules, and the binding of docetaxel locks these building blocks in place. The resulting microtubule/docetaxel complex does not have the ability to disassemble. This adversely affects cell function because the shortening and lengthening of microtubules (termed dynamic instability) is necessary for their function as a transportation highway for the cell. Chromosomes, for example, rely upon this property of microtubules during mitosis. Further research has indicated that docetaxel induces programmed cell death (apoptosis) in cancer cells by binding to an apoptosis stopping protein called Bcl-2 (B-cell leukemia 2) and thus arresting its function.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Tubulin 69 Target ID: CHEMBL2095182 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18281755	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Breast cancer 434 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020449s075lbl.pdf	Primary	Approved 8429	TAXOTERE Approved Use INDICATIONS & USAGE Docetaxel injection concentrate is a microtubule inhibitor indicated for: Breast Cancer (BC): single agent for locally advanced or metastatic BC after chemotherapy failure; and with doxorubicin and cyclophosphamide as adjuvant treatment of operable node-positive BC (1.1) Non-Small Cell Lung Cancer (NSCLC): single agent for locally advanced or metastatic NSCLC after platinum therapy failure; and with cisplatin for unresectable, locally advanced or metastatic untreated NSCLC (1.2) Hormone Refractory Prostate Cancer (HRPC): with prednisone in androgen independent (hormone refractory) metastatic prostate cancer (1.3) Gastric Adenocarcinoma (GC): with cisplatin and fluorouracil for untreated, advanced GC, including the gastroesophageal junction (1.4) Squamous Cell Carcinoma of the Head and Neck Cancer (SCCHN): with cisplatin and fluorouracil for induction treatment of locally advanced SCCHN (1.5) 1.1 Breast Cancer Docetaxel injection concentrate is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy. Docetaxel injection concentrate in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with operable node-positive breast cancer. 1.2 Non-Small Cell Lung Cancer Docetaxel injection concentrate as a single agent is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of prior platinum-based chemotherapy. Docetaxel injection concentrate in combination with cisplatin is indicated for the treatment of patients with unresectable, locally advanced or metastatic non-small cell lung cancer who have not previously received chemotherapy for this condition. 1.3 Prostate Cancer Docetaxel injection concentrate in combination with prednisone is indicated for the treatment of patients with androgen independent (hormone refractory) metastatic prostate cancer. 1.4 Gastric Adenocarcinoma Docetaxel injection concentrate in combination with cisplatin and fluorouracil is indicated for the treatment of patients with advanced gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have not received prior chemotherapy for advanced disease. 1.5 Head and Neck Cancer Docetaxel injection concentrate in combination with cisplatin and fluorouracil is indicated for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). Launch Date 1996
Non-small cell lung cancer 206 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020449s075lbl.pdf	Primary	Approved 8429	TAXOTERE Approved Use INDICATIONS & USAGE Docetaxel injection concentrate is a microtubule inhibitor indicated for: Breast Cancer (BC): single agent for locally advanced or metastatic BC after chemotherapy failure; and with doxorubicin and cyclophosphamide as adjuvant treatment of operable node-positive BC (1.1) Non-Small Cell Lung Cancer (NSCLC): single agent for locally advanced or metastatic NSCLC after platinum therapy failure; and with cisplatin for unresectable, locally advanced or metastatic untreated NSCLC (1.2) Hormone Refractory Prostate Cancer (HRPC): with prednisone in androgen independent (hormone refractory) metastatic prostate cancer (1.3) Gastric Adenocarcinoma (GC): with cisplatin and fluorouracil for untreated, advanced GC, including the gastroesophageal junction (1.4) Squamous Cell Carcinoma of the Head and Neck Cancer (SCCHN): with cisplatin and fluorouracil for induction treatment of locally advanced SCCHN (1.5) 1.1 Breast Cancer Docetaxel injection concentrate is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy. Docetaxel injection concentrate in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with operable node-positive breast cancer. 1.2 Non-Small Cell Lung Cancer Docetaxel injection concentrate as a single agent is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of prior platinum-based chemotherapy. Docetaxel injection concentrate in combination with cisplatin is indicated for the treatment of patients with unresectable, locally advanced or metastatic non-small cell lung cancer who have not previously received chemotherapy for this condition. 1.3 Prostate Cancer Docetaxel injection concentrate in combination with prednisone is indicated for the treatment of patients with androgen independent (hormone refractory) metastatic prostate cancer. 1.4 Gastric Adenocarcinoma Docetaxel injection concentrate in combination with cisplatin and fluorouracil is indicated for the treatment of patients with advanced gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have not received prior chemotherapy for advanced disease. 1.5 Head and Neck Cancer Docetaxel injection concentrate in combination with cisplatin and fluorouracil is indicated for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). Launch Date 1996
Head and neck squamous cell carcinoma 32 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020449s075lbl.pdf	Primary	Approved 8429	TAXOTERE Approved Use INDICATIONS & USAGE Docetaxel injection concentrate is a microtubule inhibitor indicated for: Breast Cancer (BC): single agent for locally advanced or metastatic BC after chemotherapy failure; and with doxorubicin and cyclophosphamide as adjuvant treatment of operable node-positive BC (1.1) Non-Small Cell Lung Cancer (NSCLC): single agent for locally advanced or metastatic NSCLC after platinum therapy failure; and with cisplatin for unresectable, locally advanced or metastatic untreated NSCLC (1.2) Hormone Refractory Prostate Cancer (HRPC): with prednisone in androgen independent (hormone refractory) metastatic prostate cancer (1.3) Gastric Adenocarcinoma (GC): with cisplatin and fluorouracil for untreated, advanced GC, including the gastroesophageal junction (1.4) Squamous Cell Carcinoma of the Head and Neck Cancer (SCCHN): with cisplatin and fluorouracil for induction treatment of locally advanced SCCHN (1.5) 1.1 Breast Cancer Docetaxel injection concentrate is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy. Docetaxel injection concentrate in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with operable node-positive breast cancer. 1.2 Non-Small Cell Lung Cancer Docetaxel injection concentrate as a single agent is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of prior platinum-based chemotherapy. Docetaxel injection concentrate in combination with cisplatin is indicated for the treatment of patients with unresectable, locally advanced or metastatic non-small cell lung cancer who have not previously received chemotherapy for this condition. 1.3 Prostate Cancer Docetaxel injection concentrate in combination with prednisone is indicated for the treatment of patients with androgen independent (hormone refractory) metastatic prostate cancer. 1.4 Gastric Adenocarcinoma Docetaxel injection concentrate in combination with cisplatin and fluorouracil is indicated for the treatment of patients with advanced gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have not received prior chemotherapy for advanced disease. 1.5 Head and Neck Cancer Docetaxel injection concentrate in combination with cisplatin and fluorouracil is indicated for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). Launch Date 1996
Gastric adenocarcinoma 12 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020449s075lbl.pdf	Primary	Approved 8429	TAXOTERE Approved Use INDICATIONS & USAGE Docetaxel injection concentrate is a microtubule inhibitor indicated for: Breast Cancer (BC): single agent for locally advanced or metastatic BC after chemotherapy failure; and with doxorubicin and cyclophosphamide as adjuvant treatment of operable node-positive BC (1.1) Non-Small Cell Lung Cancer (NSCLC): single agent for locally advanced or metastatic NSCLC after platinum therapy failure; and with cisplatin for unresectable, locally advanced or metastatic untreated NSCLC (1.2) Hormone Refractory Prostate Cancer (HRPC): with prednisone in androgen independent (hormone refractory) metastatic prostate cancer (1.3) Gastric Adenocarcinoma (GC): with cisplatin and fluorouracil for untreated, advanced GC, including the gastroesophageal junction (1.4) Squamous Cell Carcinoma of the Head and Neck Cancer (SCCHN): with cisplatin and fluorouracil for induction treatment of locally advanced SCCHN (1.5) 1.1 Breast Cancer Docetaxel injection concentrate is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy. Docetaxel injection concentrate in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with operable node-positive breast cancer. 1.2 Non-Small Cell Lung Cancer Docetaxel injection concentrate as a single agent is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of prior platinum-based chemotherapy. Docetaxel injection concentrate in combination with cisplatin is indicated for the treatment of patients with unresectable, locally advanced or metastatic non-small cell lung cancer who have not previously received chemotherapy for this condition. 1.3 Prostate Cancer Docetaxel injection concentrate in combination with prednisone is indicated for the treatment of patients with androgen independent (hormone refractory) metastatic prostate cancer. 1.4 Gastric Adenocarcinoma Docetaxel injection concentrate in combination with cisplatin and fluorouracil is indicated for the treatment of patients with advanced gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have not received prior chemotherapy for advanced disease. 1.5 Head and Neck Cancer Docetaxel injection concentrate in combination with cisplatin and fluorouracil is indicated for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). Launch Date 1996
Hormone refractory prostate cancer 5 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020449s075lbl.pdf	Primary	Approved 8429	TAXOTERE Approved Use INDICATIONS & USAGE Docetaxel injection concentrate is a microtubule inhibitor indicated for: Breast Cancer (BC): single agent for locally advanced or metastatic BC after chemotherapy failure; and with doxorubicin and cyclophosphamide as adjuvant treatment of operable node-positive BC (1.1) Non-Small Cell Lung Cancer (NSCLC): single agent for locally advanced or metastatic NSCLC after platinum therapy failure; and with cisplatin for unresectable, locally advanced or metastatic untreated NSCLC (1.2) Hormone Refractory Prostate Cancer (HRPC): with prednisone in androgen independent (hormone refractory) metastatic prostate cancer (1.3) Gastric Adenocarcinoma (GC): with cisplatin and fluorouracil for untreated, advanced GC, including the gastroesophageal junction (1.4) Squamous Cell Carcinoma of the Head and Neck Cancer (SCCHN): with cisplatin and fluorouracil for induction treatment of locally advanced SCCHN (1.5) 1.1 Breast Cancer Docetaxel injection concentrate is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy. Docetaxel injection concentrate in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with operable node-positive breast cancer. 1.2 Non-Small Cell Lung Cancer Docetaxel injection concentrate as a single agent is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of prior platinum-based chemotherapy. Docetaxel injection concentrate in combination with cisplatin is indicated for the treatment of patients with unresectable, locally advanced or metastatic non-small cell lung cancer who have not previously received chemotherapy for this condition. 1.3 Prostate Cancer Docetaxel injection concentrate in combination with prednisone is indicated for the treatment of patients with androgen independent (hormone refractory) metastatic prostate cancer. 1.4 Gastric Adenocarcinoma Docetaxel injection concentrate in combination with cisplatin and fluorouracil is indicated for the treatment of patients with advanced gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have not received prior chemotherapy for advanced disease. 1.5 Head and Neck Cancer Docetaxel injection concentrate in combination with cisplatin and fluorouracil is indicated for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). Launch Date 1996

C_max

Value	Dose	Co-administered	Analyte	Population
742 nM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/17956601	20 mg/m² 1 times / week multiple, intravenous dose: 20 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		DOCETAXEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3737 nM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/17956601	100 mg/m² 1 times / 3 weeks multiple, intravenous dose: 100 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		DOCETAXEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
1284 nM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/17956601	20 mg/m² 1 times / week multiple, intravenous dose: 20 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		DOCETAXEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
5562 nM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/17956601	100 mg/m² 1 times / 3 weeks multiple, intravenous dose: 100 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		DOCETAXEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
0.99 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/17956601	20 mg/m² 1 times / week multiple, intravenous dose: 20 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	DOCETAXEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.74 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/17956601	100 mg/m² 1 times / 3 weeks multiple, intravenous dose: 100 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	DOCETAXEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
11.1 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022234s000lbl.pdf	100 mg/m² 1 times / hour multiple, intravenous dose: 100 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	DOCETAXEL plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
3% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022234s000lbl.pdf	100 mg/m² 1 times / hour multiple, intravenous dose: 100 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		DOCETAXEL plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
75 mg/m2 1 times / 3 weeks multiple, intravenous Dose: 75 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 75 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/8761385	unhealthy, 51 years (range: 36 - 65 years) n = 39 Health Status: unhealthy Condition: advanced breast cancer: Age Group: 51 years (range: 36 - 65 years) Sex: F Population Size: 39 Sources: https://pubmed.ncbi.nlm.nih.gov/8761385	Disc. AE: Fluid retention... AEs leading to discontinuation/dose reduction: Fluid retention (16 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/8761385
43 mg/m2 1 times / week multiple, intravenous MTD Dose: 43 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 43 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/9626217	unhealthy, 58 years (range: 41-81 years) n = 10 Health Status: unhealthy Condition: Advanced Refractory Cancer Age Group: 58 years (range: 41-81 years) Sex: M+F Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/9626217	DLT: Fatigue, Asthenia... Other AEs: Nail toxicity, Alopecia... Dose limiting toxicities: Fatigue (grade 3-4, 2 patients) Asthenia (grade 3-4, 2 patients) Skin toxicity (grade 3-4, 1 patient) Diarrhea (grade 3-4, 1 patient) Other AEs: Nail toxicity (grade 3-4, 1 patient) Alopecia (grade 2, 1 patient) Leukopenia (grade 3, 2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/9626217
52 mg/m2 1 times / week multiple, intravenous Dose: 52 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 52 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/9626217	unhealthy, 58 years (range: 41-81 years) n = 3 Health Status: unhealthy Condition: Advanced Refractory Cancer Age Group: 58 years (range: 41-81 years) Sex: M+F Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/9626217	DLT: Fatigue, Asthenia... Dose limiting toxicities: Fatigue (grade 3-4, 3 patients) Asthenia (grade 3-4, 3 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/9626217
150 mg/m2 single, intravenous Overdose Dose: 150 mg/m2 Route: intravenous Route: single Dose: 150 mg/m2 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022534s000lbl.pdf	unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022534s000lbl.pdf	Other AEs: Neutropenia, Asthenia... Other AEs: Neutropenia (severe) Asthenia (mild) Epidermal and dermal conditions Paresthesia (mild) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022534s000lbl.pdf
200 mg/m2 single, intravenous Overdose Dose: 200 mg/m2 Route: intravenous Route: single Dose: 200 mg/m2 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022534s000lbl.pdf	unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022534s000lbl.pdf	Other AEs: Neutropenia, Asthenia... Other AEs: Neutropenia (severe) Asthenia (mild) Epidermal and dermal conditions Paresthesia (mild) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022534s000lbl.pdf
60 mg/m2 1 times / 3 weeks multiple, intravenous Recommended Dose: 60 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 60 mg/m2, 1 times / 3 weeks Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022534s000lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022534s000lbl.pdf	Disc. AE: Hypersensitivity... AEs leading to discontinuation/dose reduction: Hypersensitivity (severe) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022534s000lbl.pdf
100 mg/m2 1 times / 3 weeks multiple, intravenous Dose: 100 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 100 mg/m2, 1 times / 3 weeks Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022534s000lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022534s000lbl.pdf	Other AEs: Hepatotoxicity... Other AEs: Hepatotoxicity (grade 5) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022534s000lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	substrate 1037	substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP3A 191 P-gp 1537 CYP1A2 1054 CYP2C8 693 CYP2E1 667 CYP3A5 395 OATP1B3 350 MRP2 205 OAT2 115 OATP1A2 62 OATP1B1 406 OAT1 326 OAT3 339 OCT1 327 OCT2 355 OCT3 80 MRP4 77 BCRP 561

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A 191	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022534Orig1s000ClinPhamR.pdf#page=12 Page: 12.0	major	likely Comment: In vivo studies showed that the exposure o f docetaxel increased 2.2-fold when it was coadministered with ketoconazole, a potent inhibitor o f CYP3A4. Protease inhibitors, particularly ritonavir, may increase the exposure o f docetaxe Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022534Orig1s000ClinPhamR.pdf#page=12 Page: 12.0
BCRP 561	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18509327/ Page: -	no
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/8640817/ Page: -	no
CYP2C8 693	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/8640817/ Page: -	no
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/8640817/ Page: -	no
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/8640817/ Page: -	no
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/8640817/ Page: -	no
MRP4 77	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18509327/ Page: -	no
OAT1 326	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18509327/ Page: -	no
OAT3 339	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18509327/ Page: -	no
OATP1B1 406	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18509327/ Page: -	no
OCT1 327	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18509327/ Page: -	no
OCT2 355	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18509327/ Page: -	no
OCT3 80	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18509327/ Page: -	no
CYP3A5 395	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/8640817/ Page: -	yes
MRP2 205	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18509327/ Page: -	yes
OAT2 115	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18509327/ Page: -	yes
OATP1A2 62	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18509327/ Page: -	yes
OATP1B3 350	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18509327/ Page: -	yes
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/8736622/ Page: -	yes
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022534Orig1s000ClinPhamR.pdf#page=13 Page: 13.0	yes	yes (co-administration study) Comment: The effect o f ketoconazole (a strong CYP3A4 inhibitor) on the pharmacokinetics o f docetaxel was investigated in 7 cancer patients. Patients were randomized to receive either docetaxel (100 mg/m2 intravenous) alone or docetaxel (10 mg/m2 intravenous) in combination with ketoconazole (200 mg orally once daily for 3 days) in a crossover design with a 3-week washout period. The results o f this study indicated that the mean dose-normalized AUC o f docetaxel was increased 2.2-fold and its clearance was reduced by 49% when docetaxel was coadministration with ketoconazole Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022534Orig1s000ClinPhamR.pdf#page=13 Page: 13.0

PubMed

Title	Date	PubMed
Down-regulation of intratumoral aromatase messenger RNA levels by docetaxel in human breast cancers.	2004 Dec 15	15623590
Primary systemic chemotherapy with sequential, dose-dense epirubicin and docetaxel for inoperable, locally advanced inflammatory breast cancer: a phase II study.	2005	16076697
Docetaxel plus epirubicin as first-line chemotherapy in MBC (KCSG 01-10-05): phase II trial and the predictive values of circulating HER2 extracellular domain and vascular endothelial growth factor.	2005 Aug	16012734
Clinical response to neoadjuvant docetaxel predicts improved outcome in patients with large locally advanced breast cancers.	2005 Dec	16261403
Focal adhesion kinase silencing augments docetaxel-mediated apoptosis in ovarian cancer cells.	2005 Dec 15	16361572
Enhanced Bax in oral SCC in relation to antitumor effects of chemotherapy.	2005 Feb	15641988
Randomized phase II trial of the anti-angiogenic potential of doxorubicin and docetaxel; primary chemotherapy as Biomarker Discovery Laboratory.	2005 Jan	15692762
Morphological and morphometric analysis of paclitaxel and docetaxel-induced peripheral neuropathy in rats.	2005 Jul	15913989
HER-2/neu expression as a predictor of response to neoadjuvant docetaxel in patients with operable breast carcinoma.	2005 Jun 1	15834928
Farnesyltransferase inhibitor R115777 (Zarnestra, Tipifarnib) synergizes with paclitaxel to induce apoptosis and mitotic arrest and to inhibit tumor growth of multiple myeloma cells.	2005 Jun 15	15728126
Cyclooxygenase-2 inhibitor celecoxib augments chemotherapeutic drug-induced apoptosis by enhancing activation of caspase-3 and -9 in prostate cancer cells.	2005 Jun 20	15688368
A phase I/II study of exisulind in combination with docetaxel/carboplatin in patients with metastatic non-small-cell lung cancer.	2005 May	15943897
A phase I/II dose-escalation study of exisulind and docetaxel in patients with hormone-refractory prostate cancer.	2005 May	15839914
Differential effect of anti-apoptotic genes Bcl-xL and c-FLIP on sensitivity of MCF-7 breast cancer cells to paclitaxel and docetaxel.	2005 May-Jun	16080463
Life-threatening complications from doxorubicin-docetaxel chemotherapy for breast cancer.	2005 Nov 2	16264153
PAR1-mediated NFkappaB activation promotes survival of prostate cancer cells through a Bcl-xL-dependent mechanism.	2005 Oct 15	16052512
[Antisense RNA targeting survivin enhances the chemosensitivity of LOVO/Adr cells to taxotere].	2005 Sep	16224667
Docetaxel induces p53-dependent apoptosis and synergizes with farnesyl transferase inhibitor r115777 in human epithelial cancer cells.	2005 Sep 1	15970518
Metronomic low-dose chemotherapy boosts CD95-dependent antiangiogenic effect of the thrombospondin peptide ABT-510: a complementation antiangiogenic strategy.	2005 Sep 15	16166447
MRP2 (ABCC2) transports taxanes and confers paclitaxel resistance and both processes are stimulated by probenecid.	2005 Sep 20	15849751
Phase I study of S-1 and biweekly docetaxel combination chemotherapy for advanced and recurrent gastric cancer.	2006 Apr	16525670
Bortezomib inhibits docetaxel-induced apoptosis via a p21-dependent mechanism in human prostate cancer cells.	2006 Aug	16928825
Schedule dependent efficacy of gefitinib and docetaxel for bladder cancer.	2006 Aug	16813948
Synergistic effects of docetaxel and S-1 by modulating the expression of metabolic enzymes of 5-fluorouracil in human gastric cancer cell lines.	2006 Aug 15	16557585
Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer.	2006 Feb 23	16495393
Induction of tubulin by docetaxel is associated with p53 status in human non small cell lung cancer cell lines.	2006 Jan 15	16080190
Enhancement of antitumor activity of docetaxel by celecoxib in lung tumors.	2006 Jan 15	16052515
Vitamin D compounds: clinical development as cancer therapy and prevention agents.	2006 Jul-Aug	16886663
Docetaxel induces apoptosis in hormone refractory prostate carcinomas during multiple treatment cycles.	2006 Jun 5	16685278
Small molecule, oligonucleotide-based telomerase template inhibition in combination with cytolytic therapy in an in vitro androgen-independent prostate cancer model.	2006 Mar-Apr	16520278
Sequential combination of flavopiridol and docetaxel reduces the levels of X-linked inhibitor of apoptosis and AKT proteins and stimulates apoptosis in human LNCaP prostate cancer cells.	2006 May	16731754
Enhanced sensitivity to chemotherapy in esophageal cancer through inhibition of NF-kappaB.	2006 May	16337965
Sequential combinations of flavopiridol and docetaxel inhibit prostate tumors, induce apoptosis, and decrease angiogenesis in the Ggamma/T-15 transgenic mouse model of prostate cancer.	2006 Oct 1	16921509
Azidothymidine and cisplatin increase p14ARF expression in OVCAR-3 ovarian cancer cell line.	2006 Oct 1	16797627
The in vitro anti-tumour activity of zoledronic acid and docetaxel at clinically achievable concentrations in prostate cancer.	2007	17562444
Toxicity of dose-dense docetaxel followed by doxorubicin with cyclophosphamide as adjuvant therapy for breast cancer in a phase II study.	2007 Aug	17919350
[Comparison of efficacy of docetaxel combined cisplatin (TP regimen) and cisplatin combined 5-fluorouracil (PF regimen) on locally advanced nasopharyngeal carcinoma].	2007 Aug	17697552
Anticancer drugs and hyperthermia enhance cytotoxicity induced by polyamine enzymatic oxidation products.	2007 Aug	17610128
Docetaxel-induced apoptosis in melanoma cells is dependent on activation of caspase-2.	2007 Feb	17308071
Gene amplification and expression in lung cancer cells with acquired paclitaxel resistance.	2007 Feb	17284363
Gene expression profiling of breast cancer patients treated with docetaxel, doxorubicin, and cyclophosphamide within the GEPARTRIO trial: HER-2, but not topoisomerase II alpha and microtubule-associated protein tau, is highly predictive of tumor response.	2007 Feb	17010609
Docetaxel-induced apoptosis of human melanoma is mediated by activation of c-Jun NH2-terminal kinase and inhibited by the mitogen-activated protein kinase extracellular signal-regulated kinase 1/2 pathway.	2007 Feb 15	17317842
Down-regulation of inhibitor of apoptosis proteins by deguelin selectively induces apoptosis in breast cancer cells.	2007 Jan	17035597
p-53 gene mutations as a predictive marker in a population of advanced breast cancer patients randomly treated with doxorubicin or docetaxel in the context of a phase III clinical trial.	2007 Jun	17369602
Docetaxel-induced growth inhibition and apoptosis in androgen independent prostate cancer cells are enhanced by 1alpha,25-dihydroxyvitamin D3.	2007 Mar 8	16644109
Phase I/II trial of adjuvant dose-dense docetaxel/epirubicin/cyclophosphamide (TEC) in stage II and III breast cancer.	2007 May-Jun	17461902
Epigenetic inactivation of the CHFR gene in cervical cancer contributes to sensitivity to taxanes.	2007 Oct	17786301
Diethylstilbestrol and docetaxel: a Phase II study of tubulin active agents in patients with metastatic, androgen-independent prostate cancer.	2007 Sep 1	17639587
Weekly docetaxel, zoledronic acid and estramustine in hormone-refractory prostate cancer (HRPC).	2008 Feb	17846704
Pulmonary toxicity in patients treated with gemcitabine plus vinorelbine or docetaxel for advanced non-small cell lung cancer: outcome data on a randomized phase II study.	2008 Feb	17805486

Patents

Sample Use Guides

In Vivo Use Guide

Breast Cancer: 60 mg/m2 to 100 mg/m2 administered intravenously over 1 hour every 3 weeks. Non-Small Cell Lung Cancer: 75 mg/m2 administered intravenously over 1 hour every 3 weeks. Prostate Cancer: 75 mg/m2 every 3 weeks as a 1 hour intravenous infusion. Gastric Adenocarcinoma: 75 mg/m2 as a 1 hour intravenous infusion, followed by cisplatin 75 mg/m2 , as a 1 to 3 hour intravenous infusion (both on day 1 only), followed by fluorouracil 750 mg/m2 per day given as a 24-hour continuous intravenous infusion for 5 days, starting at the end of the cisplatin infusion Head and Neck Cancer: Induction chemotherapy followed by radiotherapy: For the induction treatment of locally advanced inoperable SCCHN, the recommended dose of TAXOTERE (docetaxel) is 75 mg/m2 as a 1 hour intravenous infusion followed by cisplatin 75 mg/m2 intravenously over 1 hour, on day one, followed by fluorouracil as a continuous intravenous infusion at 750 mg/m2 per day for five days. This regimen is administered every 3 weeks for 4 cycles. Following chemotherapy, patients should receive radiotherapy.

Route of Administration: Intravenous

In Vitro Use Guide

The in vitro antiproliferative effect of docetaxel (Taxotere), paclitaxel (Taxol) and cisplatin was assessed in a range of human tumour types, including 25 tumour cell lines and 35 primary cultures. In all comparisons docetaxel and paclitaxel were much more potent than cisplatin with IC50 values of the taxoids being in the nanomolar range. Docetaxel generally was two- to four-fold more cytotoxic than paclitaxel. The sensitivity profile of the cell lines, which was based on the IC50 values, indicated a certain degree of cross-sensitivity between paclitaxel and docetaxel (linear regression analysis; r = 0.73, p < 0.001

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:38:30 GMT 2023` Edited by `admin` on `Fri Dec 15 15:38:30 GMT 2023`
Record UNII	699121PHCA
Record Status	`Validated (UNII)`
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Name

Type

Language

DOCETAXEL ANHYDROUS

Common Name

English

DOCETAXEL TEVA

Brand Name

English

BIND 014

Common Name

English

docetaxel [INN]

Common Name

English

BIND 014 [WHO-DD]

Common Name

English

DOCETAXEL WINTHROP

Brand Name

English

DOCETAXEL KABI

Brand Name

English

(2R,3S)-N-CARBOXY-3-PHENYLISOSERINE, N-TERT-BUTYL ESTER, 13-ESTER WITH 5.BETA.,20-EPOXY-1,2.ALPHA.,4,7.BETA.,10.BETA.,13.ALPHA.-HEXAHYDROXYTAX-11-EN-9-ONE 4-ACETATE 2-BENZOATE

Common Name

English

DOCEFREZ

Brand Name

English

DOCETAXEL [MI]

Common Name

English

Docetaxel anhydrous [WHO-DD]

Common Name

English

DOCETAXEL [HSDB]

Common Name

English

CABAZITAXEL METABOLITE (RP56976)

Common Name

English

DOCETAXEL [JAN]

Common Name

English

NSC-628503

Code

English

DOCETAXEL TEVA PHARMA

Brand Name

English

DOCETAXEL, ANHYDROUS

Common Name

English

RP56976

Common Name

English

CKD-810

Code

English

DOCETAXEL MYLAN

Brand Name

English

DOCETAXEL ACCORD

Brand Name

English

Classification Tree Code System Code

EMA ASSESSMENT REPORTS

DOCETAXEL WINTHROP (AUTHORIZED: STOMACH NEOPLASMS)