Docetaxel Information
Docetaxel (Docetaxel) . Indications And Usage
Docetaxel (Docetaxel) Injection is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy.
Docetaxel (Docetaxel) Injection in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with operable node-positive breast cancer.
Docetaxel (Docetaxel) Injection 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 (Docetaxel) Injection 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.
Docetaxel (Docetaxel) . Dosage And Administration
For all indications, toxicities may warrant dosage adjustments .
Administer in a facility equipped to manage possible complications (e.g. anaphylaxis).
Docetaxel (Docetaxel) . Warnings And Precautions
Patients with combined abnormalities of transaminases and alkaline phosphatase should not be treated with Docetaxel (Docetaxel) Injection .
Perform frequent peripheral blood cell counts on all patients receiving Docetaxel (Docetaxel) Injection. Patients should not be retreated with subsequent cycles of Docetaxel (Docetaxel) Injection until neutrophils recover to a level >1500 cells/mm and platelets recover to a level > 100,000 cells/mm.
A 25% reduction in the dose of Docetaxel (Docetaxel) Injection is recommended during subsequent cycles following severe neutropenia (
Neutropenia (
Febrile neutropenia occurred in about 12% of patients given 100 mg/m but was very uncommon in patients given 60 mg/m. Hematologic responses, febrile reactions and infections, and rates of septic death for different regimens are dose related .
Three breast cancer patients with severe liver impairment (bilirubin >1.7 times ULN) developed fatal gastrointestinal bleeding associated with severe drug-induced thrombocytopenia. In gastric cancer patients treated with Docetaxel (Docetaxel) in combination with cisplatin and fluorouracil (TCF), febrile neutropenia and/or neutropenic infection occurred in 12% of patients receiving G-CSF compared to 28% who did not. Patients receiving TCF should be closely monitored during the first and subsequent cycles for febrile neutropenia and neutropenic infection
Patients should be observed closely for hypersensitivity reactions, especially during the first and second infusions. Severe hypersensitivity reactions characterized by generalized rash/erythema, hypotension and/or bronchospasm, or very rarely fatal anaphylaxis, have been reported in patients premedicated with 3 days of corticosteroids. Severe hypersensitivity reactions require immediate discontinuation of the Docetaxel (Docetaxel) Injection infusion and aggressive therapy. Patients with a history of severe hypersensitivity reactions should not be rechallenged with Docetaxel (Docetaxel) Injection.
Hypersensitivity reactions may occur within a few minutes following initiation of a Docetaxel (Docetaxel) Injection infusion. If minor reactions such as flushing or localized skin reactions occur, interruption of therapy is not required. All patients should be premedicated with an oral corticosteroid prior to the initiation of the infusion of Docetaxel (Docetaxel) Injection
Severe fluid retention has been reported following Docetaxel (Docetaxel) therapy. Patients should be premedicated with oral corticosteroids prior to each Docetaxel (Docetaxel) Injection administration to reduce the incidence and severity of fluid retention Patients with pre-existing effusions should be closely monitored from the first dose for the possible exacerbation of the effusions.
When fluid retention occurs, peripheral edema usually starts in the lower extremities and may become generalized with a median weight gain of 2 kg.
Among 92 breast cancer patients premedicated with 3-day corticosteroids, moderate fluid retention occurred in 27.2% and severe fluid retention in 6.5%. The median cumulative dose to onset of moderate or severe fluid retention was 819 mg/m. Nine of 92 patients (9.8%) of patients discontinued treatment due to fluid retention: 4 patients discontinued with severe fluid retention; the remaining 5 had mild or moderate fluid retention. The median cumulative dose to treatment discontinuation due to fluid retention was 1021 mg/m. Fluid retention was completely, but sometimes slowly, reversible with a median of 16 weeks from the last infusion of Docetaxel (Docetaxel) to resolution (range: 0 to 42+ weeks). Patients developing peripheral edema may be treated with standard measures, ., salt restriction, oral diuretic(s).
Docetaxel (Docetaxel) Injection can cause fetal harm when administered to a pregnant woman. Docetaxel (Docetaxel) caused embryofetal toxicities including intrauterine mortality when administered to pregnant rats and rabbits during the period of organogenesis. Embryofetal effects in animals occurred at doses as low as 1/50 and 1/300 the recommended human dose on a body surface area basis.
There are no adequate and well-controlled studies in pregnant women using Docetaxel (Docetaxel) Injection. If Docetaxel (Docetaxel) Injection is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant during therapy with Docetaxel (Docetaxel) Injection
Docetaxel (Docetaxel) . Adverse Reactions
The most serious adverse reactions from Docetaxel (Docetaxel) are:
The most common adverse reactions across all Docetaxel (Docetaxel) indications are infections, neutropenia, anemia, febrile neutropenia, hypersensitivity, thrombocytopenia, neuropathy, dysgeusia, dyspnea, constipation, anorexia, nail disorders, fluid retention, asthenia, pain, nausea, diarrhea, vomiting, mucositis, alopecia, skin reactions, and myalgia. Incidence varies depending on the indication.
Adverse reactions are described according to indication. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Responding patients may not experience an improvement in performance status on therapy and may experience worsening. The relationship between changes in performance status, response to therapy, and treatment-related side effects has not been established.
Docetaxel (Docetaxel) . Overdosage
There is no known antidote for Docetaxel (Docetaxel) Injection overdosage. In case of overdosage, the patient should be kept in a specialized unit where vital functions can be closely monitored. Anticipated complications of overdosage include: bone marrow suppression, peripheral neurotoxicity, and mucositis. Patients should receive therapeutic G-CSF as soon as possible after discovery of overdose. Other appropriate symptomatic measures should be taken, as needed.
In two reports of overdose, one patient received 150 mg/m and the other received 200 mg/m as 1-hour infusions. Both patients experienced severe neutropenia, mild asthenia, cutaneous reactions, and mild paresthesia, and recovered without incident.
In mice, lethality was observed following single intravenous doses that were ≥154 mg/kg (about 4.5 times the human dose of 100 mg/m on a mg/m basis); neurotoxicity associated with paralysis, non-extension of hind limbs, and myelin degeneration was observed in mice at 48 mg/kg (about 1.5 times the human dose of 100 mg/m basis). In male and female rats, lethality was observed at a dose of 20 mg/kg (comparable to the human dose of 100 mg/m on a mg/m basis) and was associated with abnormal mitosis and necrosis of multiple organs.
Docetaxel (Docetaxel) . Description
Docetaxel (Docetaxel) is an antineoplastic agent belonging to the taxoid family. It is prepared by semisynthesis beginning with a precursor extracted from the renewable needle biomass of yew plants. The chemical name for Docetaxel (Docetaxel) is (2R,3S)-N-carboxy-3-phenylisoserine,N--butyl ester, 13-ester with 5β-20-epoxy-1,2α,4,7β,10β,13α-hexahydroxytax-11-en-9-one 4-acetate 2-benzoate. Docetaxel (Docetaxel) has the following structural formula:
Docetaxel (Docetaxel) is a white to off-white powder with an empirical formula of CHNO, and a molecular weight of 807.88. It is highly lipophilic and practically insoluble in water.
Docetaxel (Docetaxel) Injection is a clear yellow to brownish-yellow viscous solution. Docetaxel (Docetaxel) Injection is sterile, non-pyrogenic, and is available in single-dose vials containing 20 mg (0.5 mL) or 80 mg (2 mL) Docetaxel (Docetaxel) (anhydrous). Each mL contains 40 mg Docetaxel (Docetaxel) (anhydrous), 60 mg dehydrated alcohol and 1040 mg polysorbate 80. Citric acid (anhydrous) may be used to adjust the pH.
Docetaxel (Docetaxel) Injection requires dilution with Diluent prior to addition to the infusion bag. A sterile, non-pyrogenic, single-dose diluent is supplied for that purpose. The diluent for Docetaxel (Docetaxel) Injection contains 13% polyethylene glycol 400 in water for injection, and is supplied in vials.
Docetaxel (Docetaxel) . Clinical Studies
The safety and efficacy of Docetaxel (Docetaxel) in combination with prednisone in patients with androgen independent (hormone refractory) metastatic prostate cancer were evaluated in a randomized multicenter active control trial. A total of 1006 patients with Karnofsky Performance Status (KPS) ≥60 were randomized to the following treatment groups:
All 3 regimens were administered in combination with prednisone 5 mg twice daily, continuously.
In the Docetaxel (Docetaxel) every three week arm, a statistically significant overall survival advantage was demonstrated compared to mitoxantrone. In the Docetaxel (Docetaxel) weekly arm, no overall survival advantage was demonstrated compared to the mitoxantrone control arm. Efficacy results for the Docetaxel (Docetaxel) every 3 week arm versus the control arm are summarized in Table 19 and Figure 5.
A multicenter, open-label, randomized trial was conducted to evaluate the safety and efficacy of Docetaxel (Docetaxel) for the treatment of patients with advanced gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who had not received prior chemotherapy for advanced disease. A total of 445 patients with KPS >70 were treated with either Docetaxel (Docetaxel) (T) (75 mg/m on day 1) in combination with cisplatin (C) (75 mg/m on day 1) and fluorouracil (F) (750 mg/m per day for 5 days) or cisplatin (100 mg/m on day 1) and fluorouracil (1000 mg/m per day for 5 days). The length of a treatment cycle was 3 weeks for the TCF arm and 4 weeks for the CF arm. The demographic characteristics were balanced between the two treatment arms. The median age was 55 years, 71% were male, 71% were Caucasian, 24% were 65 years of age or older, 19% had a prior curative surgery and 12% had palliative surgery. The median number of cycles administered per patient was 6 (with a range of 1 to 16) for the TCF arm compared to 4 (with a range of 1 to 12) for the CF arm. Time to progression (TTP) was the primary endpoint and was defined as time from randomization to disease progression or death from any cause within 12 weeks of the last evaluable tumor assessment or within 12 weeks of the first infusion of study drugs for patients with no evaluable tumor assessment after randomization. The hazard ratio (HR) for TTP was 1.47 (CF/TCF, 95% CI: 1.19 to 1.83) with a significantly longer TTP (p=0.0004) in the TCF arm. Approximately 75% of patients had died at the time of this analysis. Overall survival was significantly longer (p=0.0201) in the TCF arm with a HR of 1.29 (95% CI: 1.04 to 1.61). Efficacy results are summarized in Table 20 and Figures 6 and 7.
Subgroup analyses were consistent with the overall results across age, gender and race.
Docetaxel (Docetaxel) . How Supplied/storage And Handling
Docetaxel (Docetaxel) Injection is supplied in a single-use vial as a sterile, pyrogen-free, non-aqueous, viscous solution with an accompanying sterile, non-pyrogenic, Diluent (13% polyethylene glycol 400 in water for injection) vial.
Docetaxel (Docetaxel) Injection 80 mg/2 mL (NDC 16729-228-50) Docetaxel (Docetaxel) Injection 80 mg/2 mL: 80 mg Docetaxel (Docetaxel) in 2 mL polysorbate 80 and Diluent for Docetaxel (Docetaxel) Injection 80 mg (13% (w/v) polyethylene glycol 400 in water for injection). Both items are in a blister pack in one carton.
Docetaxel (Docetaxel) Injection 20 mg/0.5 mL (NDC 16729-120-49) Docetaxel (Docetaxel) Injection 20 mg/0.5 mL: 20 mg Docetaxel (Docetaxel) in 0.5 mL polysorbate 80 and Diluent for Docetaxel (Docetaxel) Injection 20 mg (13% (w/v) polyethylene glycol 400 in water for injection). Both items are in a blister pack in one carton.
Docetaxel (Docetaxel) . Patient Counseling Information
Docetaxel (Docetaxel)
Docetaxel (Docetaxel) Package Label-principal Display Panel - Mg/ - Before Initial Dilution
NDC 16729--31
Rx Only 20 mg/0.5 mL Docetaxel (Docetaxel) in polysorbate 80
Docetaxel (Docetaxel) Package Label-principal Display Panel - Mg-diluent
NDC 16729--31
(13% polyethylene glycol 400 in water for injection)
Rx Only
Docetaxel (Docetaxel) Package Label-principal Display Panel - Mg/ Ml -before Initial Dilution
NDC 16729--33
Rx Only
80 mg/2 mL Docetaxel (Docetaxel) in polysorbate 80
Docetaxel (Docetaxel) Package Label-principal Display Panel - Mg-diluent
NDC 16729--33
(13% polyethylene glycol 400 in water for injection)
Rx Only
Docetaxel (Docetaxel) Package Label-principal Display Panel - Carton - Ndc --
NDC 16729--49
Rx Only * see side panel for concentration obtained after initial dilution step
Each Docetaxel (Docetaxel) Injection Vial, NDC 16729-120-31 contains 20 mg / 0.5 mL Docetaxel (Docetaxel) in polysorbate 80
Each Diluent for Docetaxel (Docetaxel) Injection Vial, NDC 16729-121-31 contains approxi- mately 1.95 mL of 13% (wv) polyethylene glycol 400 in water for injection. Single-dose vials
Docetaxel (Docetaxel) Package Label-principal Display Panel - Carton - Ndc --
NDC 16729--50
Rx Only * see side panel for concentration obtained after initial dilution step
Each Docetaxel (Docetaxel) Injection Vial, NDC 16729-120-33 contains 80 mg / 2 mL Docetaxel (Docetaxel) in polysorbate 80
Each Diluent for Docetaxel (Docetaxel) Injection Vial, NDC 16729-121-33 contains approxi- mately 7.2 mL of 13% (wv) polyethylene glycol 400 in water for injection. Single-dose vials
