Font size

Email to a Friend

> Home > Oncology > About Taxotere® > Mechanism Of Action

Important Safety Info.

Clinical Pharmacology

Mechanism Of Action

Pharmacokinetics Profile

Drug Interactions

Adverse Events

Learn more about The PACT+ ^SM Program.

Keep dosing at your fingertips

Pre-med sheets for Breast, Lung, Prostate, Gastric, and Head and Neck Cancer.

Mechanism of Action

The antitumor activity of Taxotere^® (docetaxel) is derived from its ability to disrupt the normal process of microtubule assembly and disassembly.^*,1,2

Microtubules are cylindrical structures that form the basis of the cellular skeleton and are essential to the reproduction, growth and spread of tumor cells.^*,1 Normally, as a part of the mitotic process, microtubules are reorganized to form a spindle. Assembly of microtubules from tubulin requires the presence of guanosine triphosphate (GTP).^*,1,2

Dividing cell demonstrating microtubule spindle

Dividing cell demonstrating ^*,1 microtubule spindle

Taxotere^® binds tubulin, promoting polymerization and preventing depolymerization of microtubules in the absence of GTP.^*,2 It binds to the ß-subunit of the tubulin within the microtubule, promoting the formation of stable microtubules, which form abnormal bundles that do the following:

Resist physiologic disassembly
Accumulate within tumor cells
Inhibit cell proliferation leading to cell death

Microtubule and the presence of Taxotere®

Microtubule and the presence of Taxotere^®

In addition, research has found Taxotere^® to have:

A high binding affinity to tubulin and is a potent promoter of microtubule formation^*,3,4
Increased cellular uptake and slow efflux^*,5

* Preclinical data may not necessarily be indicative of clinical efficacy and safety.

References

Bissery M-C, Nohynek G, Sanderink G-J, Lavelle F. Docetaxel (Taxotere^®): a review of preclinical and clinical experience. Part 1: preclinical experience. Anticancer Drugs. 1995;6:339-355.
Eisenhauer EA, Vermorken JB. The taxoids: comparative clinical pharmacology and therapeutic potential. Drugs. 1998;55:5-30.
Ringel I, Horwitz SB. Studies with RP 56976 (Taxotere^®): a semisynthetic afalogue of Taxol. J Natl Cancer Inst. 1991;83:288-291
Díaz JF, Andreu JM. Assembly of purified GDP-tubulin into microtubules induced by Taxol and Taxotere^®: reversibility, ligand stoichiometry, and competition. Biochemistry. 1993;32:2747-2755.
Riou J-F, Petitgenet O, Combeau C, Lavelle F. Cellular uptake and efflux of docetaxel (Taxotere^®) and paclitaxel (Taxol^®) in P388 cell line. Proc Am Assoc Cancer Res. 1994;35:385. Abstract 2292.

WARNING

Taxotere® should be administered only under the supervision of a qualified physician experienced in the use of antineoplastic agents. Appropriate management of complications is possible only when adequate diagnostic and treatment facilities are readily available
The incidence of treatment-related mortality associated with Taxotere® therapy is increased in patients with abnormal liver function, in patients receiving higher doses, and in patients with non-small cell lung carcinoma and a history of prior treatment with platinum-based chemotherapy who receive Taxotere® as a single agent at a dose of 100 mg/m² (see WARNINGS section of the prescribing information)
Taxotere® should generally not be given to patients with bilirubin > upper limit of normal (ULN), or to patients with serum glutamic-oxaloacetic transferase (SGOT) and/or serum glutamic-pyruvic transferase (SGPT) > 1.5 X ULN concomitant with alkaline phosphatase > 2.5 X ULN
- Patients with elevations of bilirubin or abnormalities of transaminase concurrent with alkaline phosphatase are at increased risk for the development of grade 4 neutropenia, febrile neutropenia, infections, severe thrombocytopenia, severe stomatitis, severe skin toxicity, and toxic death
- Patients with isolated elevations of transaminase > 1.5 X ULN also had a higher rate of febrile neutropenia grade 4 but did not have an increased incidence of toxic death
- Bilirubin, SGOT or SGPT, and alkaline phosphatase values should be obtained prior to each cycle of Taxotere® therapy and reviewed by the treating physician
Taxotere® therapy should not be given to patients with neutrophil counts of < 1500 cells/mm³
- In order to monitor the occurrence of neutropenia, which may be severe and result in infection, frequent blood-cell counts should be performed on all patients receiving Taxotere®
Severe hypersensitivity reactions characterized by generalized rash/erythema, hypotension and/or bronchospasm, or very rarely fatal anaphylaxis, have been reported in patients who received the recommended 3-day dexamethasone premedication
- Patients should be observed closely for hypersensitivity reactions, especially during the first and second infusions
Taxotere® must not be given to patients who have a history of severe hypersensitivity reactions to Taxotere® or to other drugs formulated with polysorbate 80
- All patients should be premedicated with oral corticosteroids such as dexamethasone (see DOSAGE AND ADMINISTRATION section of the prescribing information)
Severe fluid retention occurred in 6.5% (6/92) of patients despite use of a 3-day dexamethasone premedication regimen. It was characterized by one or more of the following events: poorly tolerated peripheral edema, generalized edema, pleural effusion requiring urgent drainage, dyspnea at rest, cardiac tamponade, or pronounced abdominal distention (due to ascites) (see PRECAUTIONS section of the prescribing information)

Additional Warnings

Treatment-related acute myeloid leukemia (AML) or myelodysplasia has occurred in patients given anthracyclines and/or cyclophosphamide, including use with Taxotere® in adjuvant therapy of breast cancer

Taxotere® can cause fetal harm when administered to pregnant women. Women of childbearing potential should be advised to avoid becoming pregnant during therapy with Taxotere®

Precautions

Localized erythema of the extremities with edema followed by desquamation has been observed

— In case of severe skin toxicity, an adjustment in dosage is recommended (see DOSAGE AND ADMINISTRATION section of the prescribing information)

Severe neurosensory symptoms (paresthesia, dysesthesia, pain) were observed in 5.5% (53/965) of metastatic breast cancer patients, and resulted in treatment discontinuation in 6.1%

— When these symptoms occur, dosage must be adjusted; if symptoms persist, treatment should be discontinued (see DOSAGE AND ADMINISTRATION section of the prescribing information)

Severe asthenia was reported in 14.9% (144/965) of metastatic breast cancer patients, but led to treatment discontinuation in only 1.8%

— Symptoms of fatigue and weakness may last a few days up to several weeks and may be associated with deterioration of performance status in patients with progressive disease

In patients treated with TCF for gastric cancer, the incidence of serious adverse events was higher in patients >65 years than in younger patients. Adverse events (all grades) occurring at rates >10% higher in elderly patients included lethargy, stomatitis, diarrhea, dizziness, edema, and febrile neutropenia/neutropenic infection.

Please see important safety information and full prescribing information, including boxed WARNING.

Taxotere Indications

Breast Cancer
TAXOTERE® is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy
TAXOTERE® in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with operable node-positive breast cancer

Non-Small Cell Lung Cancer
TAXOTERE®, as a single agent, is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of prior platinum-based chemotherapy
TAXOTERE® in combination with cisplatin is indicated for the treatment of patients with unresectable, locally advanced or metastatic NSCLC who have not previously received chemotherapy for this condition.

Prostate Cancer
TAXOTERE® in combination with prednisone is indicated for the treatment of patients with androgen independent (hormone refractory) metastatic prostate cancer.

Gastric Cancer
TAXOTERE® in combination with cisplatin and flouroucil is indicated for the treatment of patients with advanced gastric adenocercinoma, including adenocarcinoma of the gastroesophageal junction, who have not received prior chemotherapy for advanced disease.

Head and neck Cancer
TAXOTERE® in combination with cisplatin and flourouracil is indicated for the induction treatment of patients with locally advanced squamous cell cercinoma of the head and neck (SCCHN).