Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C51H68N2O15 |
| Molecular Weight | 949.09 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 11 / 11 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
[H][C@]12[C@H](OC(=O)C3=CC=CC=C3)[C@]4(O)C[C@H](OC(=O)[C@H](OC(=O)CCCN(CC)CC)[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=ZTUNLNJLXRFYQL-FSBDEDPYSA-N
InChI=1S/C51H68N2O15/c1-11-53(12-2)25-19-24-36(56)65-40(38(31-20-15-13-16-21-31)52-46(61)68-47(5,6)7)45(60)64-33-27-51(62)43(66-44(59)32-22-17-14-18-23-32)41-49(10,42(58)39(57)37(29(33)3)48(51,8)9)34(55)26-35-50(41,28-63-35)67-30(4)54/h13-18,20-23,33-35,38-41,43,55,57,62H,11-12,19,24-28H2,1-10H3,(H,52,61)/t33-,34-,35+,38-,39+,40+,41-,43-,49+,50-,51+/m0/s1
| Molecular Formula | C51H68N2O15 |
| Molecular Weight | 949.09 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 10 / 11 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
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.
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL2095182 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | TAXOTERE Approved UseINDICATIONS & 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 Date1996 |
|||
| Primary | TAXOTERE Approved UseINDICATIONS & 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 Date1996 |
|||
| Primary | TAXOTERE Approved UseINDICATIONS & 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 Date1996 |
|||
| Primary | TAXOTERE Approved UseINDICATIONS & 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 Date1996 |
|||
| Primary | TAXOTERE Approved UseINDICATIONS & 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 Date1996 |
Cmax
| 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 |
T1/2
| Value | Dose | Co-administered | 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 |
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 |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
3% |
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: |
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: |
Disc. AE: Fluid retention... AEs leading to discontinuation/dose reduction: Fluid retention (16 patients) Sources: |
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: |
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: |
DLT: Fatigue, Asthenia... Other AEs: Nail toxicity, Alopecia... Dose limiting toxicities: Fatigue (grade 3-4, 2 patients) Other AEs:Asthenia (grade 3-4, 2 patients) Skin toxicity (grade 3-4, 1 patient) Diarrhea (grade 3-4, 1 patient) Nail toxicity (grade 3-4, 1 patient) Sources: Alopecia (grade 2, 1 patient) Leukopenia (grade 3, 2 patients) |
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: |
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: |
DLT: Fatigue, Asthenia... Dose limiting toxicities: Fatigue (grade 3-4, 3 patients) Sources: Asthenia (grade 3-4, 3 patients) |
150 mg/m2 single, intravenous Overdose Dose: 150 mg/m2 Route: intravenous Route: single Dose: 150 mg/m2 Sources: |
unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: |
Other AEs: Neutropenia, Asthenia... Other AEs: Neutropenia (severe) Sources: Asthenia (mild) Epidermal and dermal conditions Paresthesia (mild) |
200 mg/m2 single, intravenous Overdose Dose: 200 mg/m2 Route: intravenous Route: single Dose: 200 mg/m2 Sources: |
unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: |
Other AEs: Neutropenia, Asthenia... Other AEs: Neutropenia (severe) Sources: Asthenia (mild) Epidermal and dermal conditions Paresthesia (mild) |
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: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Disc. AE: Hypersensitivity... AEs leading to discontinuation/dose reduction: Hypersensitivity (severe) Sources: |
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: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Other AEs: Hepatotoxicity... Other AEs: Hepatotoxicity (grade 5) Sources: |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Fluid retention | 16 patients Disc. AE |
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: |
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: |
| Alopecia | grade 2, 1 patient | 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: |
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: |
| Leukopenia | grade 3, 2 patients | 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: |
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: |
| Nail toxicity | grade 3-4, 1 patient | 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: |
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: |
| Diarrhea | grade 3-4, 1 patient DLT |
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: |
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: |
| Skin toxicity | grade 3-4, 1 patient DLT |
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: |
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: |
| Asthenia | grade 3-4, 2 patients DLT |
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: |
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: |
| Fatigue | grade 3-4, 2 patients DLT |
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: |
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: |
| Asthenia | grade 3-4, 3 patients DLT |
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: |
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: |
| Fatigue | grade 3-4, 3 patients DLT |
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: |
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: |
| Epidermal and dermal conditions | 150 mg/m2 single, intravenous Overdose Dose: 150 mg/m2 Route: intravenous Route: single Dose: 150 mg/m2 Sources: |
unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: |
|
| Asthenia | mild | 150 mg/m2 single, intravenous Overdose Dose: 150 mg/m2 Route: intravenous Route: single Dose: 150 mg/m2 Sources: |
unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: |
| Paresthesia | mild | 150 mg/m2 single, intravenous Overdose Dose: 150 mg/m2 Route: intravenous Route: single Dose: 150 mg/m2 Sources: |
unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: |
| Neutropenia | severe | 150 mg/m2 single, intravenous Overdose Dose: 150 mg/m2 Route: intravenous Route: single Dose: 150 mg/m2 Sources: |
unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: |
| Epidermal and dermal conditions | 200 mg/m2 single, intravenous Overdose Dose: 200 mg/m2 Route: intravenous Route: single Dose: 200 mg/m2 Sources: |
unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: |
|
| Asthenia | mild | 200 mg/m2 single, intravenous Overdose Dose: 200 mg/m2 Route: intravenous Route: single Dose: 200 mg/m2 Sources: |
unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: |
| Paresthesia | mild | 200 mg/m2 single, intravenous Overdose Dose: 200 mg/m2 Route: intravenous Route: single Dose: 200 mg/m2 Sources: |
unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: |
| Neutropenia | severe | 200 mg/m2 single, intravenous Overdose Dose: 200 mg/m2 Route: intravenous Route: single Dose: 200 mg/m2 Sources: |
unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: |
| Hypersensitivity | severe Disc. AE |
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: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
| Hepatotoxicity | grade 5 | 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: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| 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 |
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| 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 |
|---|---|---|
| A phase II trial of docetaxel and CPT-11 in patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction, and gastric cardia. | 2002 |
|
| Docetaxel in combination with dacarbazine in patients with advanced melanoma. | 2002 |
|
| Exisulind in combination with docetaxel inhibits growth and metastasis of human lung cancer and prolongs survival in athymic nude rats with orthotopic lung tumors. | 2002 Mar |
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| Treatment of advanced breast cancer with docetaxel and gemcitabine with and without human granulocyte colony-stimulating factor. | 2002 May |
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| Atrial fibrillation during adjuvant chemotherapy with docetaxel: a case report. | 2002 Nov-Dec |
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| A phase II trial of gemcitabine and docetaxel in patients with chemotherapy-naive, advanced nonsmall cell lung carcinoma. | 2002 Oct 15 |
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| Cystic maculopathy with normal capillary permeability secondary to docetaxel. | 2003 Apr |
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| Bone pain associated with once-per-cycle pegfilgrastim is similar to daily filgrastim in patients with breast cancer. | 2003 Feb |
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| Docetaxel enhances the therapeutic effect of the angiogenesis inhibitor TNP-470 (AGM-1470) in metastatic human transitional cell carcinoma. | 2003 Feb |
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| Amelioration of docetaxel/cisplatin induced polyneuropathy by alpha-lipoic acid. | 2003 Feb |
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| Docetaxel-related skin, nail, and vascular toxicity. | 2003 Jan |
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| Increased frequency of venous thromboembolism with the combination of docetaxel and thalidomide in patients with metastatic androgen-independent prostate cancer. | 2003 Mar |
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| Reversible life-threatening encephalopathy in the absence of hepatic failure following conventional doses of docetaxel. | 2003 May |
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| Phase II clinical trial of carboplatin and docetaxel in patients with metastatic ovarian cancer: active combination with low incidence of peripheral neuropathy. | 2003 May-Jun |
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| Pulmonary toxicity during prostate cancer treatment with docetaxel and thalidomide. | 2003 May-Jun |
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| ERK inhibitor PD98059 enhances docetaxel-induced apoptosis of androgen-independent human prostate cancer cells. | 2003 Nov 10 |
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| HER-2/neu as a predictive marker in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin or single-agent docetaxel. | 2004 Aug |
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| Genome-wide discovery of loci influencing chemotherapy cytotoxicity. | 2004 Aug 10 |
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| Docetaxel versus paclitaxel for adjuvant treatment of ovarian cancer: case-control analysis of toxicity. | 2004 Feb |
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| The proteasome inhibitor bortezomib enhances the activity of docetaxel in orthotopic human pancreatic tumor xenografts. | 2004 Jan |
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| All-trans retinoic acid potentiates Taxotere-induced cell death mediated by Jun N-terminal kinase in breast cancer cells. | 2004 Jan 15 |
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| Use of gabapentin in the prevention of taxane-induced arthralgias and myalgias. | 2004 May 1 |
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| Primary systemic chemotherapy with sequential, dose-dense epirubicin and docetaxel for inoperable, locally advanced inflammatory breast cancer: a phase II study. | 2005 |
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| Clinical response to neoadjuvant docetaxel predicts improved outcome in patients with large locally advanced breast cancers. | 2005 Dec |
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| Morphological and morphometric analysis of paclitaxel and docetaxel-induced peripheral neuropathy in rats. | 2005 Jul |
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| 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 |
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| A phase I/II dose-escalation study of exisulind and docetaxel in patients with hormone-refractory prostate cancer. | 2005 May |
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| 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 |
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| [Antisense RNA targeting survivin enhances the chemosensitivity of LOVO/Adr cells to taxotere]. | 2005 Sep |
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| Docetaxel induces p53-dependent apoptosis and synergizes with farnesyl transferase inhibitor r115777 in human epithelial cancer cells. | 2005 Sep 1 |
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| Metronomic low-dose chemotherapy boosts CD95-dependent antiangiogenic effect of the thrombospondin peptide ABT-510: a complementation antiangiogenic strategy. | 2005 Sep 15 |
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| MRP2 (ABCC2) transports taxanes and confers paclitaxel resistance and both processes are stimulated by probenecid. | 2005 Sep 20 |
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| Phase I study of S-1 and biweekly docetaxel combination chemotherapy for advanced and recurrent gastric cancer. | 2006 Apr |
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| 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 |
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| Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. | 2006 Feb 23 |
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| Induction of tubulin by docetaxel is associated with p53 status in human non small cell lung cancer cell lines. | 2006 Jan 15 |
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| Docetaxel induces apoptosis in hormone refractory prostate carcinomas during multiple treatment cycles. | 2006 Jun 5 |
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| Small molecule, oligonucleotide-based telomerase template inhibition in combination with cytolytic therapy in an in vitro androgen-independent prostate cancer model. | 2006 Mar-Apr |
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| Azidothymidine and cisplatin increase p14ARF expression in OVCAR-3 ovarian cancer cell line. | 2006 Oct 1 |
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| Toxicity of dose-dense docetaxel followed by doxorubicin with cyclophosphamide as adjuvant therapy for breast cancer in a phase II study. | 2007 Aug |
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| Anticancer drugs and hyperthermia enhance cytotoxicity induced by polyamine enzymatic oxidation products. | 2007 Aug |
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| Docetaxel-induced apoptosis in melanoma cells is dependent on activation of caspase-2. | 2007 Feb |
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| Gene amplification and expression in lung cancer cells with acquired paclitaxel resistance. | 2007 Feb |
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| 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 |
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| Down-regulation of inhibitor of apoptosis proteins by deguelin selectively induces apoptosis in breast cancer cells. | 2007 Jan |
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| Docetaxel-induced growth inhibition and apoptosis in androgen independent prostate cancer cells are enhanced by 1alpha,25-dihydroxyvitamin D3. | 2007 Mar 8 |
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| Epigenetic inactivation of the CHFR gene in cervical cancer contributes to sensitivity to taxanes. | 2007 Oct |
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| Diethylstilbestrol and docetaxel: a Phase II study of tubulin active agents in patients with metastatic, androgen-independent prostate cancer. | 2007 Sep 1 |
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| Weekly docetaxel, zoledronic acid and estramustine in hormone-refractory prostate cancer (HRPC). | 2008 Feb |
|
| 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 |
Patents
Sample Use Guides
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
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
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