For all indications, toxicities may warrant dosage adjustments. Administer in a facility equipped to manage possible complications (e.g. anaphylaxis).
For locally advanced or metastatic breast cancer after failure of prior chemotherapy, the recommended dose of DOCETAXEL is 60 mg/m² to 100 mg/m² administered intravenously over 1 hour every 3 weeks.
For the adjuvant treatment of operable node-positive breast cancer, the recommended DOCETAXEL dose is 75 mg/m² administered 1 hour after doxorubicin 50 mg/m² and cyclophosphamide 500 mg/m² every 3 weeks for 6 courses. Prophylactic G-CSF may be used to mitigate the risk of hematological toxicities.
Non-Small Cell Lung Cancer
For treatment after failure of prior platinum-based chemotherapy, DOCETAXEL 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 BOXED WARNING, WARNINGS AND PRECAUTIONS, Clinical Studies].
For chemotherapy-naïve patients, DOCETAXEL was evaluated in combination with cisplatin. The recommended dose of DOCETAXEL is 75 mg/m² administered intravenously over 1 hour immediately followed by cisplatin 75 mg/m² over 30-60 minutes every 3 weeks.
For hormone-refractory metastatic prostate cancer, the recommended dose of DOCETAXEL is 75 mg/m² every 3 weeks as a 1 hour intravenous infusion. Prednisone 5 mg orally twice daily is administered continuously.
For gastric adenocarcinoma, the recommended dose of DOCETAXEL is 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. Treatment is repeated every three weeks. Patients must receive premedication with antiemetics and appropriate hydration for cisplatin administration.
Head and Neck Cancer
Patients must receive premedication with antiemetics, and appropriate hydration (prior to and after cisplatin administration). Prophylaxis for neutropenic infections should be administered. All patients treated on the DOCETAXEL containing arms of the TAX323 and TAX324 studies received prophylactic antibiotics.
Induction chemotherapy followed by radiotherapy (TAX323)
For the induction treatment of locally advanced inoperable SCCHN, the recommended dose of 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..
Induction chemotherapy followed by chemoradiotherapy (TAX324)
For the induction treatment of patients with locally advanced (unresectable, low surgical cure, or organ preservation) SCCHN, the recommended dose of DOCETAXEL is 75 mg/m² as a 1 hour intravenous infusion on day 1, followed by cisplatin 100 mg/m² administered as a 30-minute to 3 hour infusion, followed by fluorouracil 1000 mg/m²/day as a continuous infusion from day 1 to day 4. This regimen is administered every 3 weeks for 3 cycles. Following chemotherapy, patients should receive chemoradiotherapy.
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 DOCETAXEL administration in order to reduce the incidence and severity of fluid retention as well as the severity of hypersensitivity reactions [see BOXED WARNING, WARNINGS AND PRECAUTIONS].
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 DOCETAXEL infusion [see WARNINGS AND PRECAUTIONS].
Dosage Adjustments During Treatment
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 DOCETAXEL 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 DOCETAXEL therapy may tolerate higher doses. Patients who develop ≥ grade 3 peripheral neuropathy should have DOCETAXEL treatment discontinued entirely.
Combination Therapy with DOCETAXEL in the Adjuvant Treatment of Breast Cancer
DOCETAXEL in combination with doxorubicin and cyclophosphamide should be administered when the neutrophil count is ≥ 1,500 cells/mm³. Patients who experience febrile neutropenia should receive G-CSF in all subsequent cycles. Patients who continue to experience this reaction should remain on G-CSF and have their DOCETAXEL dose reduced to 60 mg/m². Patients who experience grade 3 or 4 stomatitis should have their DOCETAXEL dose decreased to 60 mg/m². Patients who experience severe or cumulative cutaneous reactions or moderate neurosensory signs and/or symptoms during DOCETAXEL therapy should have their dosage of DOCETAXEL reduced from 75 to 60 mg/m². If the patient continues to experience these reactions at 60 mg/m², treatment should be discontinued.
Non-Small Cell Lung Cancer
Monotherapy with DOCETAXEL 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 DOCETAXEL 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 DOCETAXEL treatment discontinued entirely.
Combination therapy with DOCETAXEL for chemotherapy-naïve NSCLC
For patients who are dosed initially at DOCETAXEL 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 DOCETAXEL 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 DOCETAXEL for hormone-refractory metastatic prostate cancer
DOCETAXEL 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 DOCETAXEL therapy should have the dosage of DOCETAXEL reduced from 75 to 60 mg/m². If the patient continues to experience these reactions at 60 mg/m², the treatment should be discontinued.
Gastric or Head and Neck Cancer
DOCETAXEL in combination with cisplatin and fluorouracil in gastric cancer or head and neck cancer
Patients treated with DOCETAXEL in combination with cisplatin and fluorouracil must receive antiemetics and appropriate hydration according to current institutional guidelines. In both studies, G-CSF was recommended during the second and/or subsequent cycles in case of febrile neutropenia, or documented infection with neutropenia, or neutropenia lasting more than 7 days. If an episode of febrile neutropenia, prolonged neutropenia or neutropenic infection occurs despite G-CSF use, the DOCETAXEL dose should be reduced from 75 to 60 mg/m². If subsequent episodes of complicated neutropenia occur the DOCETAXEL dose should be reduced from 60 to 45 mg/m². In case of grade 4 thrombocytopenia the DOCETAXEL dose should be reduced from 75 to 60 mg/m². Patients should not be retreated with subsequent cycles of DOCETAXEL until neutrophils recover to a level > 1,500 cells/mm³ and platelets recover to a level > 100,000 cells/mm³. Discontinue treatment if these toxicities persist. [see WARNINGS AND PRECAUTIONS].
The dose modifications for cisplatin and fluorouracil in the gastric cancer study are provided below:
Cisplatin dose modifications and delays
Peripheral neuropathy: A neurological examination should be performed before entry into the study, and then at least every 2 cycles and at the end of treatment. In the case of neurological signs or symptoms, more frequent examinations should be performed and the following dose modifications can be made according to NCIC-CTC grade:
Grade 2: Reduce cisplatin dose by 20%.
Grade 3: Discontinue treatment.
Ototoxicity: In the case of grade 3 toxicity, discontinue treatment.
Nephrotoxicity: In the event of a rise in serum creatinine ≥ grade 2 ( > 1.5 x normal value) despite adequate rehydration, CrCl should be determined before each subsequent cycle and the following dose reductions should be considered (see Table 2).
Fluorouracil dose modifications and treatment delays
In the event of grade 2 or greater plantar-palmar toxicity, fluorouracil should be stopped until recovery. The fluorouracil dosage should be reduced by 20%.
For other greater than grade 3 toxicities, except alopecia and anemia, chemotherapy should be delayed (for a maximum of 2 weeks from the planned date of infusion) until resolution to grade ≤ 1 and then recommenced, if medically appropriate.
For other fluorouracil dosage adjustments, also refer to the manufacturers' prescribing information.
Combination Therapy with Strong CYP3A4 inhibitors
Avoid using concomitant strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and voriconazole). There are no clinical data with a dose adjustment in patients receiving strong CYP3A4 inhibitors. Based on extrapolation from a pharmacokinetic study with ketoconazole in 7 patients, consider a 50% docetaxel dose reduction if patients require co-administration of a strong CYP3A4 inhibitor.
DOCETAXEL is a cytotoxic anticancer drug and, as with other potentially toxic compounds, caution should be exercised when handling and preparing DOCETAXEL solutions. The use of gloves is recommended. Please refer to [see HOW SUPPLIED/ Storage and Handling]. If DOCETAXEL 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 DOCETAXEL 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 DOCETAXEL 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 DOCETAXEL dilution for infusion should be stored in bottles (glass, polypropylene) or plastic bags (polypropylene, polyolefin) and administered through polyethylene-lined administration sets.
Two-vial formulation (Injection Concentrate and Diluent)
DOCETAXEL Injection Concentrate requires two dilutions prior to administration. Please follow the preparation instructions provided below. Note: Both the DOCETAXEL 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 DOCETAXEL 20 mg and DOCETAXEL 80 mg.
Preparation and Administration
DO NOT use the two-vial formulation (Injection Concentrate and diluent) with the one-vial formulation.
Two-vial formulation (Injection Concentrate and Diluent)
A.Initial Diluted Solution
DOCETAXEL vials should be stored between 2°C and 25°C (36°F and 77°F). If the vials are stored under refrigeration, allow the appropriate number of vials of DOCETAXEL Injection Concentrate and diluent (13% ethanol in water for injection) vials to stand at room temperature for approximately 5 minutes.
Aseptically withdraw the entire contents of the appropriate diluent vial (approximately 1.8 mL for DOCETAXEL 20 mg and approximately 7.1 mL for DOCETAXEL 80 mg) into a syringe by partially inverting the vial, and transfer it to the appropriate vial of DOCETAXEL Injection Concentrate. If the procedure is followed as described, an initial diluted solution of 10 mg docetaxel/mL will result.
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.
The initial diluted DOCETAXEL 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.
B.Final Dilution for Infusion
Aseptically withdraw the required amount of initial diluted DOCETAXEL solution (10 mg docetaxel/mL) with a calibrated syringe and inject into 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 DOCETAXEL is required, use a larger volume of the infusion vehicle so that a concentration of 0.74 mg/mL DOCETAXEL is not exceeded.
Thoroughly mix the infusion by manual rotation.
As with all parenteral products, DOCETAXEL should be inspected visually for particulate matter or discoloration prior to administration whenever the solution and container permit. If the DOCETAXEL initial diluted solution or final dilution for intravenous infusion is not clear or appears to have precipitation, these should be discarded.
The final DOCETAXEL dilution for infusion should be administered intravenously as a 1-hour infusion under ambient room temperature and lighting conditions.
DOCETAXEL final dilution for infusion, if stored between 2°C and 25°C (36°F and 77°F) is stable for 4 hours. DOCETAXEL final dilution for infusion (in either 0.9% Sodium Chloride solution or 5% Dextrose solution) should be used within 4 hours (including the 1 hour intravenous administration).