Taxotere (Docetaxel) - Indications and Dosage

INDICATIONS AND USAGE

Breast Cancer: TAXOTERE is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy.

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 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 non-small cell lung cancer 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.

DOSAGE AND ADMINISTRATION

Breast Cancer: The recommended dose of TAXOTERE is 60-100 mg/m² administered intravenously over 1 hour every 3 weeks.

Non-Small Cell Lung Cancer: For treatment after failure of prior platinum-based chemotherapy, TAXOTERE was evaluated as monotherapy, and the recommended dose is 75 mg/m² administered intravenously over 1 hour every 3 weeks. A dose of 100 mg/m² in patients previously treated with chemotherapy was associated with increased hematologic toxicity, infection, and treatment-related mortality in randomized, controlled trials (see BOX WARNING, WARNINGS and CLINICAL STUDIES sections).

For chemotherapy-naïve patients, TAXOTERE was evaluated in combination with cisplatin. The recommended dose of TAXOTERE is 75 mg/m² administered intravenously over 1 hour immediately followed by cisplatin 75 mg/m² over 30-60 minutes every 3 weeks.

Prostate cancer: For hormone-refractory metastatic prostate cancer, the recommended dose of TAXOTERE is 75 mg/m² every 3 weeks as a 1 hour infusion. Prednisone 5 mg orally twice daily is administered continuously.

Premedication Regimen: All patients should be premedicated with oral corticosteroids (see below for prostate cancer) such as dexamethasone 16 mg per day (e.g., 8 mg BID) for 3 days starting 1 day prior to TAXOTERE administration in order to reduce the incidence and severity of fluid retention as well as the severity of hypersensitivity reactions (see BOX WARNING, WARNINGS, and PRECAUTIONS sections).

For hormone-refractory metastatic prostate cancer, given the concurrent use of prednisone, the recommended premedication regimen is oral dexamethasone 8 mg, at 12 hours, 3 hours and 1 hour before the TAXOTERE infusion (see WARNINGS, and PRECAUTIONS sections).

DOSAGE ADJUSTMENTS DURING TREATMENT

Breast Cancer: Patients who are dosed initially at 100 mg/m² and who experience either febrile neutropenia, neutrophils < 500 cells/mm³ for more than 1 week, or severe or cumulative cutaneous reactions during TAXOTERE therapy should have the dosage adjusted from 100 mg/m² to 75 mg/m². If the patient continues to experience these reactions, the dosage should either be decreased from 75 mg/m² to 55 mg/m² or the treatment should be discontinued. Conversely, patients who are dosed initially at 60 mg/m² and who do not experience febrile neutropenia, neutrophils <500 cells/mm³ for more than 1 week, severe or cumulative cutaneous reactions, or severe peripheral neuropathy during TAXOTERE therapy may tolerate higher doses. Patients who develop ≥ grade 3 peripheral neuropathy should have TAXOTERE treatment discontinued entirely.

NON-SMALL CELL LUNG CANCER:

MONOTHERAPY WITH TAXOTERE FOR NSCLC TREATMENT AFTER FAILURE OF PRIOR PLATINUM-BASED CHEMOTHERAPY

Patients who are dosed initially at 75 mg/m² and who experience either febrile neutropenia, neutrophils <500 cells/mm³ for more than one week, severe or cumulative cutaneous reactions, or other grade 3/4 non-hematological toxicities during TAXOTERE treatment should have treatment withheld until resolution of the toxicity and then resumed at 55 mg/m². Patients who develop ≥ grade 3 peripheral neuropathy should have TAXOTERE treatment discontinued entirely.

COMBINATION THERAPY WITH TAXOTERE FOR CHEMOTHERAPY-NA&IUML;VE NSCLC

For patients who are dosed initially at TAXOTERE 75 mg/m² in combination with cisplatin, and whose nadir of platelet count during the previous course of therapy is <25,000 cells/mm³, in patients who experience febrile neutropenia, and in patients with serious non-hematologic toxicities, the TAXOTERE dosage in subsequent cycles should be reduced to 65 mg/m². In patients who require a further dose reduction, a dose of 50 mg/m² is recommended. For cisplatin dosage adjustments, see manufacturers' prescribing information.

COMBINATION THERAPY WITH TAXOTERE FOR HORMONE-REFRACTORY METASTATIC PROSTATE CANCER

TAXOTERE should be administered when the neutrophil count is ≥ 1,500 cells/mm³. Patients who experience either febrile neutropenia, neutrophils < 500 cells/mm³ for more than one week, severe or cumulative cutaneous reactions or moderate neurosensory signs and/or symptoms during TAXOTERE therapy should have the dosage of TAXOTERE reduced from 75 to 60 mg/m². If the patient continues to experience these reactions at 60 mg/m², the treatment should be discontinued.

SPECIAL POPULATIONS:

Hepatic Impairment: Patients with bilirubin > ULN should generally not receive TAXOTERE. Also, patients with SGOT and/or SGPT > 1.5 × ULN concomitant with alkaline phosphatase > 2.5 × ULN should generally not receive TAXOTERE.

Children: The safety and effectiveness of docetaxel in pediatric patients below the age of 16 years have not been established.

Elderly: See Precautions, Geriatric Use. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy in elderly patients.

PREPARATION AND ADMINISTRATION

ADMINISTRATION PRECAUTIONS

TAXOTERE is a cytotoxic anticancer drug and, as with other potentially toxic compounds, caution should be exercised when handling and preparing TAXOTERE solutions. The use of gloves is recommended. Please refer to Handling and Disposal section.

If TAXOTERE Injection Concentrate, initial diluted solution, or final dilution for infusion should come into contact with the skin, immediately and thoroughly wash with soap and water.

If TAXOTERE Injection Concentrate, initial diluted solution, or final dilution for infusion should come into contact with mucosa, immediately and thoroughly wash with water.

Contact of the TAXOTERE concentrate with plasticized PVC equipment or devices used to prepare solutions for infusion is not recommended. In order to minimize patient exposure to the plasticizer DEHP (di-2-ethylhexyl phthalate), which may be leached from PVC infusion bags or sets, the final TAXOTERE dilution for infusion should be stored in bottles (glass, polypropylene) or plastic bags (polypropylene, polyolefin) and administered through polyethylene-lined administration sets.

TAXOTERE Injection Concentrate requires two dilutions prior to administration. Please follow the preparation instructions provided below. Note: Both the TAXOTERE Injection Concentrate and the diluent vials contain an overfill to compensate for liquid loss during preparation. This overfill ensures that after dilution with the entire contents of the accompanying diluent, there is an initial diluted solution containing 10 mg/mL docetaxel.

The table below provides the fill range of the diluent, the approximate extractable volume of diluent when the entire contents of the diluent vial are withdrawn, and the concentration of the initial diluted solution for TAXOTERE 20 mg and TAXOTERE 80 mg.

PREPARATION AND ADMINISTRATION

1. Initial Diluted Solution
   
   1. TAXOTERE vials should be stored between 2 and 25°C (36 and 77°F). If the vials are stored under refrigeration, allow the appropriate number of vials of TAXOTERE Injection Concentrate and diluent (13% ethanol in water for injection) vials to stand at room temperature for approximately 5 minutes.
   2. Aseptically withdraw the entire contents of the appropriate diluent vial (approximately 1.8 mL for TAXOTERE 20 mg and approximately 7.1 mL for TAXOTERE 80 mg) into a syringe by partially inverting the vial, and transfer it to the appropriate vial of TAXOTERE Injection Concentrate. If the procedure is followed as described, an initial diluted solution of 10mg docetaxel/mL will result.
   3. Mix the initial diluted solution by repeated inversions for at least 45 seconds to assure full mixture of the concentrate and diluent. Do not shake.
   4. The initial diluted TAXOTERE solution (10 mg docetaxel/mL) should be clear; however, there may be some foam on top of the solution due to the polysorbate 80. Allow the solution to stand for a few minutes to allow any foam to dissipate. It is not required that all foam dissipate prior to continuing the preparation process.
      The initial diluted solution may be used immediately or stored either in the refrigerator or at room temperature for a maximum of 8 hours.
2. Final Dilution for Infusion
   
   1. Aseptically withdraw the required amount of initial diluted TAXOTERE solution (10 mg docetaxel/mL) with a calibrated syringe and injectinto a 250 mL infusion bag or bottle of either 0.9% Sodium Chloride solution or 5% Dextrose solution to produce a final concentration of 0.3 to 0.74 mg/mL.
      If a dose greater than 200 mg of TAXOTERE is required, use a larger volume of the infusion vehicle so that a concentration of 0.74 mg/mL TAXOTERE is not exceeded.
   2. Thoroughly mix the infusion by manual rotation.
   3. As with all parenteral products, TAXOTERE should be inspected visually for particulate matter or discoloration prior to administration whenever the solution and container permit. If the TAXOTERE initial diluted solution or final dilution for infusion is not clear or appears to have precipitation, these should be discarded.

The final TAXOTERE dilution for infusion should be administered intravenously as a 1-hour infusion under ambient room temperature and lighting conditions.

Stability: TAXOTERE infusion solution, if stored between 2 and 25°C (36 and 77°F) is stable for 4 hours. Fully prepared TAXOTERE infusion solution (in either 0.9% Sodium Chloride solution or 5% Dextrose solution) should be used within 4 hours (including the 1 hour i.v. administration).

HOW SUPPLIED

TAXOTERE Injection Concentrate is supplied in a single-dose vial as a sterile, pyrogen-free, non-aqueous, viscous solution with an accompanying sterile, non-pyrogenic, Diluent (13% ethanol in water for injection) vial. The following strengths are available:

TAXOTERE 80 MG/2 ML(NDC 0075-8001-80)

TAXOTERE (docetaxel) Injection Concentrate 80 mg/2 mL: 80 mg docetaxel in 2 mL polysorbate 80 and Diluent for TAXOTERE 80 mg (13% (w/w) ethanol in water for injection). Both items are in a blister pack in one carton.

TAXOTERE 20 MG/0.5 ML(NDC 0075-8001-20)

TAXOTERE (docetaxel) Injection Concentrate 20 mg/0.5 mL: 20 mg docetaxel in 0.5 mL polysorbate 80 and diluent for TAXOTERE 20 mg (13% (w/w) ethanol in water for injection). Both items are in a blister pack in one carton.

Storage: Store between 2 and 25°C (36 and 77°F). Retain in the original package to protect from bright light. Freezing does not adversely affect the product.

Handling and Disposal: Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published^1-7. There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.