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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(doe se TAKS el)
Generic Available (U.S.)
Yes: Excludes injection solution concentrate
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of breast cancer (locally advanced/metastatic or adjuvant treatment of operable node-positive); locally-advanced or metastatic nonsmall cell lung cancer (NSCLC); hormone refractory, metastatic prostate cancer; advanced gastric adenocarcinoma; locally-advanced squamous cell head and neck cancer
Use: Unlabeled
Treatment of bladder cancer (metastatic), ovarian cancer, cervical cancer (relapsed), esophageal cancer, small cell lung cancer (relapsed), soft tissue sarcoma, Ewing's sarcoma, osteosarcoma, and unknown-primary adenocarcinoma
Pregnancy Risk Factor
D
Pregnancy Considerations
Animal studies have demonstrated embryotoxicity, fetal toxicity, and maternal toxicity. There are no adequate and well-controlled studies in pregnant women; however, fetal harm may occur. Women of childbearing potential should avoid becoming pregnant. A pregnancy registry is available for all cancers diagnosed during pregnancy at Cooper Health (856-757-7876).
Lactation
Excretion in breast milk unknown/not recommended
Breast-Feeding Considerations
Due to the potential for serious adverse reactions in nursing the infant, breast-feeding is not recommended.
Contraindications
Severe hypersensitivity to docetaxel or any component of the formulation; severe hypersensitivity to other medications containing polysorbate 80; neutrophil count <1500/mm3
Warnings/Precautions
Boxed warnings:
• Bone marrow suppression: See “Concerns related to adverse effects” below.
• Fluid retention: See “Concerns related to adverse effects” below.
• Hepatic impairment: See “Disease-related concerns” below.
• Hypersensitivity reactions: See “Concerns related to adverse effects” below.
• Treatment-related mortality: See “Concerns related to adverse effects” below.
Special handling:
• Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects:
• Bone marrow suppression: [U.S. Boxed Warning]: Patients with an absolute neutrophil count <1500/mm3 should not receive docetaxel. Platelets should recover to >100,000/mm3 prior to treatment. The dose-limiting toxicity is neutropenia. Patients with increased liver function tests experienced more episodes of neutropenia with a greater number of severe infections. When administered as sequential infusions, taxane derivatives (docetaxel, paclitaxel) should be administered before platinum derivatives (carboplatin, cisplatin) to limit myelosuppression and to enhance efficacy.
• Cutaneous reactions: Cutaneous reactions, including erythema (with edema) and desquamation, have been reported; may require dose reduction.
• Fluid retention: [U.S. Boxed Warning]: Severe fluid retention, characterized by pleural effusion (requiring immediate drainage), ascites, peripheral edema (poorly tolerated), dyspnea at rest, cardiac tamponade, and weight gain (2-15 kg) has been reported. The incidence and severity of fluid retention increases sharply at cumulative doses ≥400 mg/m2. Patients should be premedicated with a corticosteroid (starting 1 day prior to administration) to prevent or reduce the severity of fluid retention. Closely monitor patients with existing effusions.
• Hypersensitivity reactions: [U.S. Boxed Warning]: Severe hypersensitivity reactions, characterized by generalized rash/erythema, hypotension, bronchospasms, or anaphylaxis may occur; do not administer to patients with a history of severe hypersensitivity to docetaxel or polysorbate 80. Minor reactions including flushing or localized skin reactions may also occur. Observe for hypersensitivity, especially with the first 2 infusions. Discontinue for severe reactions; do not rechallenge if severe. Patients should be premedicated with a corticosteroid (starting 1 day prior to administration) to prevent or reduce the severity of hypersensitivity reactions.
• Neurosensory symptoms: Dosage adjustment is recommended with severe neurosensory symptoms (paresthesia, dysesthesia, pain); persistent symptoms may require discontinuation. Reversal of symptoms may be delayed after discontinuation.
• Secondary malignancies: Treatment-related acute myeloid leukemia or myelodysplasia occurred in patients receiving docetaxel in combination with anthracyclines and/or cyclophosphamide.
• Treatment-related mortality: [U.S. Boxed Warning]: Patients with abnormal liver function, those receiving higher doses, and patients with nonsmall cell lung cancer and a history of prior treatment with platinum derivatives who receive single-agent docetaxel at a dose of 100 mg/m2 are at higher risk for treatment-related mortality.
• Weakness: Fatigue and weakness (may be severe) have been reported; symptoms may last a few days up to several weeks. In patients with progressive disease, weakness may be associated with a decrease in performance status.
Disease-related concerns:
• Hepatic impairment: [U.S. Boxed Warning]: Avoid use in patients with bilirubin exceeding upper limit of normal (ULN) or AST and/or ALT >1.5 times ULN in conjunction with alkaline phosphatase >2.5 times ULN. Patients with abnormal liver function are at increased risk of treatment-related adverse events, including grade 4 neutropenia, neutropenic fever, infections, and sever thrombocytopenia, stomatitis, skin toxicity or toxic death. Obtain liver function tests prior to each treatment cycle.
Concurrent drug therapy issues:
• CYP3A4 inhibitors: Avoid concomitant use with strong CYP3A4 inhibitors. Although data is limited, a 50% dose reduction is suggested if concomitant therapy with a strong CYP3A4 inhibitor is required.
Adverse Reactions
Percentages reported for docetaxel monotherapy; frequency may vary depending on diagnosis, dose, liver function, prior treatment, and premedication. The incidence of adverse events was usually higher in patients with elevated liver function tests.
>10%:
Cardiovascular: Fluid retention (13% to 60%; dose dependent)
Central nervous system: Neurosensory events (20% to 58%; including neuropathy), fever (31% to 35%), neuromotor events (16%)
Dermatologic: Alopecia (56% to 76%), cutaneous events (20% to 48%), nail disorder (11% to 41%)
Gastrointestinal: Stomatitis (19% to 53%; severe 1% to 8%), diarrhea (23% to 43%; severe: 5% to 6%), nausea (34% to 42%), vomiting (22% to 23%)
Hematologic: Neutropenia (84% to 99%; grade 4: 75% to 86%; nadir (median): 7 days, duration (severe neutropenia): 7 days; dose dependent), leukopenia (84% to 99%; grade 4: 32% to 44%), anemia (65% to 94%; dose dependent; grades 3/4: 8% to 9%), thrombocytopenia (8% to 14%; grade 4: 1%; dose dependent), febrile neutropenia (6% to 12%; dose dependent)
Hepatic: Transaminases increased (4% to 19%)
Neuromuscular & skeletal: Weakness (53% to 66%; severe 13% to 18%), myalgia (3% to 23%)
Respiratory: Pulmonary events (41%)
Miscellaneous: Infection (1% to 34%; dose dependent), hypersensitivity (1% to 21%; with premedication 15%)
1% to 10%:
Cardiovascular: Left ventricular ejection fraction decreased (prostate cancer: 10%; metastatic breast cancer: 8%), hypotension (3%)
Gastrointestinal: Taste perversion (6%)
Hepatic: Bilirubin increased (9%), alkaline phosphatase increased (4% to 7%)
Local: Infusion-site reactions (4%, including hyperpigmentation, inflammation, redness, dryness, phlebitis, extravasation, swelling of the vein)
Neuromuscular and skeletal: Arthralgia (3% to 9%)
Ocular: Epiphora associated with canalicular stenosis (≤77% with weekly administration; ≤1% with every 3-week administration)
<1%, postmarketing, and/or case reports (limited to important or life-threatening): Acute myeloid leukemia (AML), acute respiratory distress syndrome (ARDS), anaphylactic shock, arrhythmia, ascites, atrial fibrillation, atrial flutter, AV block, bleeding episodes, bradycardia, bronchospasm, cardiac tamponade, chest pain, chest tightness, colitis, conjunctivitis, constipation, cutaneous lupus erythematosus, deep vein thrombosis, dehydration, disseminated intravascular coagulation (DIC), drug fever, duodenal ulcer, dyspnea, dysrhythmia, ECG abnormalities, erythema multiforme, esophagitis, gastrointestinal hemorrhage, gastrointestinal obstruction, gastrointestinal perforation, hand and foot syndrome, hearing loss, heart failure, hepatitis, hypertension, ileus, interstitial pneumonia, ischemic colitis, lacrimal duct obstruction, loss of consciousness (transient), MI, multiorgan failure, myelodysplastic syndrome, myocardial ischemia, neutropenic enterocolitis, neutropenic typhlitis, ototoxicity, pericardial effusion, pleural effusion, pruritus, pulmonary edema, pulmonary embolism, pulmonary fibrosis, radiation pneumonitis, radiation recall, renal failure, renal insufficiency, scleroderma-like changes, seizure, sepsis, sinus tachycardia, Stevens-Johnson syndrome, syncope, toxic epidermal necrolysis, tachycardia, thrombophlebitis, unstable angina, visual disturbances (transient)
Metabolism/Transport Effects
Substrate of CYP3A4 (major), P-glycoprotein; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP3A4 (weak)
Drug Interactions
Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of DOCEtaxel. Risk D: Consider therapy modification
Antineoplastic Agents (Anthracycline, Systemic): Taxane Derivatives may enhance the adverse/toxic effect of Antineoplastic Agents (Anthracycline, Systemic). Taxane Derivatives may increase the serum concentration of Antineoplastic Agents (Anthracycline, Systemic). Taxane Derivatives may also increase the formation of toxic anthracycline metabolites in heart tissue. Risk D: Consider therapy modification
ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole systemic exposure/affects with concomitant use of a weak CYP3A4 inhibitor. Decrease aripiprazole dose to 25% of the usual dose in patients receiving both a CYP3A4 and a CYP2D6 inhibitor (regardless of potencies). Risk C: Monitor therapy
BCG: Immunosuppressants may diminish the therapeutic effect of BCG. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for agranulocytosis may be increased. Risk X: Avoid combination
Coccidioidin Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioidin Skin Test. Risk C: Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Risk C: Monitor therapy
Dronedarone: May increase the serum concentration of DOCEtaxel. Management: Avoid this combination whenever possible. If this combination must be used, consider using a reduced docetaxel dose, and/or increase monitoring for evidence of serious docetaxel toxicity (e.g., neutropenia, mucositis, etc.). Risk D: Consider therapy modification
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Risk X: Avoid combination
Platinum Derivatives: May enhance the myelosuppressive effect of Taxane Derivatives. Administer Taxane derivative before Platinum derivative when given as sequential infusions to limit toxicity. Risk D: Consider therapy modification
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Risk D: Consider therapy modification
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Risk C: Monitor therapy
SORAfenib: May increase the serum concentration of DOCEtaxel. Risk C: Monitor therapy
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Risk X: Avoid combination
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (due to GI irritation).
Herb/Nutraceutical: Avoid St John's wort (may decrease docetaxel levels).
Storage
Docetaxel 10 mg/mL: Store intact vials at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from bright light. Freezing does not adversely affect the product. Multi-use vials (80 mg/8 mL and 160 mg/16 mL) are stable for up to 28 days after first entry when stored between 2°C to 8°C (36°F to 46°F) and protected from light.
Docetaxel concentrate (Taxotere®) 20 mg/mL: Store intact vials between 2°C to 25°C (36°F to 77°F). Protect from bright light. Freezing does not adversely affect the product.
Docetaxel lyophilized powder (Docefrez™): Store intact vials between 2°C to 8°C (36°F to 46°F). Protect from light. Allow vials (and provided diluent) to stand at room temperature for 5 minutes prior to reconstitution. After reconstitution, may be stored refrigerated or at room temperature for up to 8 hours.
Solutions diluted for infusion should be used within 4 hours of preparation, including infusion time.
Two-vial formulation
(discontinued product):
Reconstituted solutions of the two-vial formulation are stable in the vial for 8 hours at room temperature or under refrigeration. Solutions diluted for infusion in polyolefin containers should be used within 4 hours of preparation, including infusion time.
Reconstitution
Note: Multiple concentrations: Docetaxel is available as a one-vial formulation at concentrations of 10 mg/mL (generic formulation) and 20 mg/mL (concentrate; Taxotere®, and as a lyophilized powder (Docefrez™) which is reconstituted (with provided diluent) to 20 mg/0.8 mL (20 mg vial) or 24 mg/mL (80 mg vial). Admixture errors have occurred due to the availability of various concentrations. Docetaxel was previously available as a two-vial formulation which included two vials (a concentrated docetaxel vial and a diluent vial), resulting in a reconstituted concentration of 10 mg/mL; the two-vial formulation has been discontinued by the manufacturer.
Use appropriate precautions for handling and disposal.
One-vial formulations: Further dilute for infusion in 250-500 mL of NS or D5W in a non-DEHP container (eg, glass, polypropylene, polyolefin) to a final concentration of 0.3-0.74 mg/mL. Gently rotate to mix thoroughly.
Lyophilized powder: Dilute with the provided diluent (contains ethanol in polysorbate 80); add 1 mL to each 20 mg vial (resulting concentration is 20 mg/0.8 mL) and 4 mL to each 80 mg vial (resulting concentration is 24 mg/mL). Shake well to dissolve completely. If air bubbles are present, allow to stand for a few minutes while air bubbles dissipate. Further dilute in 250 mL of NS or D5W in a non-DEHP container (eg, glass, polypropylene, polyolefin) to a final concentration of 0.3-0.74 mg/mL (for doses >200 mg, use a larger volume of NS or D5W, not to exceed a final concentration of 0.74 mg/mL). Mix thoroughly by manual agitation. Solutions diluted for infusion should be used within 4 hours of preparation, including infusion time.
Two-vial formulation
(discontinued product):
Vials should be diluted with 13% (w/w) ethanol/water (provided with the drug) to a final concentration of 10 mg/mL. Do not shake. Further dilute for infusion in 250-500 mL of NS or D5W in a non-DEHP container (eg, glass, polypropylene, polyolefin) to a final concentration of 0.3-0.74 mg/mL. Gently rotate to mix thoroughly. Do not use the two-vial formulation with the one-vial formulation for the same admixture product.
Compatibility
Stable in D5W, LR, NS.
Y-site administration: Compatible: Acyclovir, amifostine, amikacin, aminophylline, ampicillin, ampicillin/sulbactam, anidulafungin, aztreonam, bumetanide, buprenorphine, butorphanol, calcium gluconate, cefazolin, cefepime, cefotaxime, cefotetan, cefoxitin, ceftazidime, cefuroxime, chlorpromazine, cimetidine, ciprofloxacin, clindamycin, dexamethasone sodium phosphate, dexrazoxane, diphenhydramine, dobutamine, dopamine, doripenem, doxycycline, droperidol, enalaprilat, famotidine, fluconazole, furosemide, gallium nitrate, ganciclovir, gemcitabine, gentamicin, granisetron, haloperidol, heparin, hydrocortisone sodium succinate, hydromorphone, hydroxyzine, imipenem/cilastatin, leucovorin calcium, lorazepam, magnesium sulfate, mannitol, meperidine, meropenem, mesna, metoclopramide, metronidazole, minocycline, morphine, ondansetron, oxaliplatin, palonosetron, pemetrexed, piperacillin, piperacillin/tazobactam, potassium chloride, prochlorperazine edisylate, promethazine, ranitidine, sodium bicarbonate, sulfamethoxazole/trimethoprim, ticarcillin/clavulanate, tobramycin, vancomycin, zidovudine. Incompatible: Amphotericin B, doxorubicin liposome, methylprednisolone sodium succinate, nalbuphine. Variable (consult detailed reference): Ceftriaxone.
Compatibility in syringe: Incompatible: Ceftriaxone.
Mechanism of Action
Docetaxel promotes the assembly of microtubules from tubulin dimers, and inhibits the depolymerization of tubulin which stabilizes microtubules in the cell. This results in inhibition of DNA, RNA, and protein synthesis. Most activity occurs during the M phase of the cell cycle.
Pharmacodynamics/Kinetics
Exhibits linear pharmacokinetics at the recommended dosage range
Distribution: Extensive extravascular distribution and/or tissue binding; Vd: 80-90 L/m2, Vdss: 113 L (mean steady state)
Protein binding: ~94% to 97%, primarily to alpha1-acid glycoprotein, albumin, and lipoproteins
Metabolism: Hepatic; oxidation via CYP3A4 to metabolites
Half-life elimination: Terminal: ~11 hours
Excretion: Feces (~75%, <8% as unchanged drug); urine (<5%)
Dosage
Adults: I.V. infusion: Note: Premedicate with corticosteroids, beginning the day before docetaxel administration, (administer corticosteroids for 3 days) to reduce the severity of hypersensitivity reactions and fluid retention. Details concerning dosing in combination regimens should also be consulted.
Breast cancer:
Locally-advanced or metastatic: 60-100 mg/m2 every 3 weeks (as a single agent)
Operable, node-positive (adjuvant treatment): 75 mg/m2 every 3 weeks for 6 courses (in combination with doxorubicin and cyclophosphamide)
Weekly administration (unlabeled dosing): 40 mg/m2/dose once a week (as a single agent) for 6 weeks followed by a 2-week rest, repeat until disease progression or unacceptable toxicity (Burstein, 2000) or 35 mg/m2/dose once a week (in combination with trastuzumab) for 3 weeks followed by a 1-week rest; repeat until disease progression or unacceptable toxicity (Esteva, 2002)
Nonsmall cell lung cancer: 75 mg/m2 every 3 weeks (as monotherapy or in combination with cisplatin)
Prostate cancer: 75 mg/m2 every 3 weeks (in combination with prednisone)
Gastric adenocarcinoma: 75 mg/m2 every 3 weeks (in combination with cisplatin and fluorouracil)
Head and neck cancer: 75 mg/m2 every 3 weeks (in combination with cisplatin and fluorouracil) for 3 or 4 cycles, followed by radiation therapy
Bladder cancer, metastatic (unlabeled use): 100 mg/m2 every 3 weeks (as a single agent) (McCaffrey, 1997)
Esophageal cancer (unlabeled use): 75 mg/m2 every 3 weeks (in combination with cisplatin and fluorouracil) (Ajani, 2007; Van Cutsem, 2006)
Ovarian cancer (unlabeled use): 60 mg/m2 every 3 weeks (in combination with carboplatin) (Markman, 2001) or 75 mg/m2 every 3 weeks (in combination with carboplatin) (Vasey, 2004) or 35 mg/m2 (maximum dose: 70 mg) weekly for 3 weeks followed by a 1-week rest (in combination with carboplatin) (Kushner, 2007)
Soft tissue sarcoma (unlabeled use): 100 mg/m2 on day 8 of a 3-week treatment cycle (in combination with gemcitabine and filgrastim or pegfilgrastim) (Leu, 2004; Maki, 2007)
Unknown-primary, adenocarcinoma (unlabeled use): 65 mg/m2 every 3 weeks (in combination with carboplatin) (Greco, 2000) or 75 mg/m2 on day 8 of a 3-week treatment cycle (in combination with gemcitabine) (Pouessel, 2004)
Dosing adjustment for concomitant CYP3A4 inhibitors: Avoid the concomitant use of strong CYP3A4 inhibitors with docetaxel. If concomitant use of a strong CYP3A4 inhibitor cannot be avoided, consider reducing the docetaxel dose by 50% (based on limited pharmacokinetic data).
Dosing adjustment for toxicity:
Note: Toxicity includes febrile neutropenia, neutrophils ≤500/mm3 for >1 week, severe or cumulative cutaneous reactions; in nonsmall cell lung cancer, this may also include platelets <25,000/mm3 and other grade 3/4 nonhematologic toxicities.
Breast cancer (single agent): Patients dosed initially at 100 mg/m2; reduce dose to 75 mg/m2; Note: If the patient continues to experience these adverse reactions, the dosage should be reduced to 55 mg/m2 or therapy should be discontinued; discontinue for peripheral neuropathy ≥ grade 3. Patients initiated at 60 mg/m2 who do not develop toxicity may tolerate higher doses.
Breast cancer, adjuvant treatment (combination chemotherapy): TAC regimen should be administered when neutrophils are ≥1500/mm3. Patients experiencing febrile neutropenia should receive G-CSF in all subsequent cycles. Patients with persistent febrile neutropenia (while on G-CSF), patients experiencing severe/cumulative cutaneous reactions, moderate neurosensory effects (signs/symptoms) or grade 3 or 4 stomatitis should receive a reduced dose (60 mg/m2) of docetaxel. Discontinue therapy with persistent toxicities after dosage reduction.
Nonsmall cell lung cancer:
Monotherapy: Patients dosed initially at 75 mg/m2 should have dose held until toxicity is resolved, then resume at 55 mg/m2; discontinue for peripheral neuropathy ≥ grade 3.
Combination therapy (with cisplatin): Patients dosed initially at 75 mg/m2 should have the docetaxel dosage reduced to 65 mg/m2 in subsequent cycles; if further adjustment is required, dosage may be reduced to 50 mg/m2
Prostate cancer: Reduce dose to 60 mg/m2; discontinue therapy if toxicities persist at lower dose.
Gastric cancer, head and neck cancer: Note: Cisplatin may require dose reductions/therapy delays for peripheral neuropathy, ototoxicity, and/or nephrotoxicity. Patients experiencing febrile neutropenia, documented infection with neutropenia or neutropenia >7 days should receive G-CSF in all subsequent cycles. For neutropenic complications despite G-CSF use, further reduce dose to 60 mg/m2. Neutropenic complications in subsequent cycles should be further dose reduced to 45 mg/m2. Patients who experience grade 4 thrombocytopenia should receive a dose reduction from 75 mg/m2 to 60 mg/m2. Discontinue therapy for persistent toxicities.
Gastrointestinal toxicity for docetaxel in combination with cisplatin and fluorouracil for treatment of gastric cancer or head and neck cancer:
Diarrhea, grade 3:
First episode: Reduce fluorouracil dose by 20%
Second episode: Reduce docetaxel dose by 20%
Diarrhea, grade 4:
First episode: Reduce fluorouracil and docetaxel doses by 20%
Second episode: Discontinue treatment
Stomatitis, grade 3:
First episode: Reduce fluorouracil dose by 20%
Second episode: Discontinue fluorouracil for all subsequent cycles
Third episode: Reduce docetaxel dose by 20%
Stomatitis, grade 4:
First episode: Discontinue fluorouracil for all subsequent cycles
Second episode: Reduce docetaxel dose by 20%
Dosing adjustment in renal impairment: Renal excretion is minimal (<5%), therefore, the need for dosage adjustments for renal dysfunction is unlikely (Li, 2007). Not removed by hemodialysis, may be administered before or after hemodialysis (Janus, 2010).
Dosing adjustment in hepatic impairment:
The FDA-approved labeling recommends the following adjustments:
Total bilirubin greater than the ULN, or AST and/or ALT >1.5 times ULN concomitant with alkaline phosphatase >2.5 times ULN: Use is not recommended.
Hepatic impairment dosing adjustment specific for gastric adenocarcinoma:
AST/ALT >2.5 to ≤5 times ULN and alkaline phosphatase ≤2.5 times ULN: Administer 80% of dose
AST/ALT >1.5 to ≤5 times ULN and alkaline phosphatase >2.5 to ≤5 times ULN: Administer 80% of dose
AST/ALT >5 times ULN and /or alkaline phosphatase >5 times ULN: Discontinue docetaxel
The following guidelines have been used by some clinicians (Floyd, 2006):
Transaminases 1.6-6 times ULN: Administer 75% of dose
Transaminases >6 times ULN: Use clinical judgment
Dosage: Combination Regimens
Breast cancer:
Capecitabine + Docetaxel (Breast Cancer)
Docetaxel-Bevacizumab
Docetaxel-Cyclophosphamide (TC)
Docetaxel-Doxorubicin (Breast Cancer)
Docetaxel-FEC
Docetaxel-Trastuzumab
Docetaxel-Trastuzumab-Carboplatin
Docetaxel-Trastuzumab-Cisplatin
Docetaxel-Trastuzumab-FEC
Docetaxel (Weekly)-Trastuzumab
Doxorubicin (Liposomal)-Docetaxel (Breast Cancer)
TAC
Esophageal cancer:
Docetaxel-Cisplatin-Fluorouracil (Gastric/Esophageal Cancer)
Docetaxel-Oxaliplatin-Fluorouracil (Esophageal Cancer)
Docetaxel-Oxaliplatin-Leucovorin-Fluorouracil (Esophageal Cancer)
Gastric cancer:
Capecitabine-Docetaxel (Gastric Cancer)
Docetaxel-Cisplatin-Fluorouracil (Gastric/Esophageal Cancer)
Head and neck cancer: Docetaxel-Cisplatin-Fluorouracil (Head and Neck Cancer)
Lung cancer (nonsmall cell):
Capecitabine + Docetaxel (NSCLC)
Docetaxel-Cisplatin
Osteosarcoma: Gemcitabine-Docetaxel (Sarcoma)
Ovarian cancer:
Docetaxel-Carboplatin (Ovarian Cancer)
Docetaxel (Ovarian Regimen)
Docetaxel-Oxaliplatin (Ovarian Cancer)
Prostate cancer:
Docetaxel-Prednisone
Docetaxel (Weekly Regimen)
Estramustine + Docetaxel
Estramustine + Docetaxel + Calcitriol
Estramustine + Docetaxel + Carboplatin
Estramustine + Docetaxel + Hydrocortisone
Estramustine + Docetaxel + Prednisone
Soft tissue sarcoma: Gemcitabine-Docetaxel (Sarcoma)
Unknown primary, adenocarcinoma:
Docetaxel-Carboplatin (Unknown Primary)
Docetaxel-Cisplatin (Unknown Primary)
Gemcitabine-Docetaxel (Unknown Primary)
Unknown primary, squamous cell: Docetaxel-Cisplatin-Fluorouracil (Unknown Primary)
Administration: I.V.
Administer I.V. infusion over 1-hour through nonsorbing polyethylene lined (non-DEHP) tubing; in-line filter is not necessary (the use of a filter during administration is not recommended by the manufacturer). Infusion should be completed within 4 hours of final preparation. Note: Premedication with corticosteroids for 3 days, beginning the day before docetaxel administration, is recommended to prevent hypersensitivity reactions and fluid retention (see Additional Information or Pharmacotherapy Pearls).
Monitoring Parameters
CBC with differential, liver function tests, bilirubin, alkaline phosphatase, renal function; monitor for hypersensitivity reactions, neurosensory symptoms, gastrointestinal toxicity (eg, diarrhea, stomatitis), cutaneous reactions, fluid retention, epiphora, and canalicular stenosis
Patient Education
This medication can only be administered by infusion; report immediately any pain, burning, swelling, or redness at infusion site, difficulty breathing or swallowing, chest pain, or sudden chills. It is important to maintain adequate nutrition and hydration, unless instructed to restrict fluid intake. Ensure premedication prior to administration to prevent hypersensitivity. You will be more susceptible to infection. May cause nausea or vomiting, loss of hair (reversible), or diarrhea. Report immediately swelling of extremities, respiratory difficulty, unusual weight gain, abdominal distention, chest pain, palpitations, fever, chills, unusual bruising or bleeding, signs of infection, excessive fatigue, or rash.
Additional Information
Premedication with oral corticosteroids is recommended to decrease the incidence and severity of fluid retention and severity of hypersensitivity reactions. The manufacturer recommends dexamethasone 16 mg/day (8 mg twice daily) orally for 3 days, starting the day before docetaxel administration; for prostate cancer, when prednisone is part of the antineoplastic regimen, dexamethasone 8 mg orally is administered at 12 hours, 3 hours, and 1 hour prior to docetaxel.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Mucositis, stomatitis, and taste perversion.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause confusion
Mental Health: Effects on Psychiatric Treatment
May cause leukopenia; use caution with clozapine and carbamazepine
Nursing: Physical Assessment/Monitoring
Severe hypersensitivity reactions have been reported; premedication with dexamethasone may be advisable. Patient should be monitored continuously during infusion; dosing adjustment may be necessary. Monitor for neutropenia, severe fluid retention, pleural effusion, opportunistic infections, and anemia prior to each infusion and on a regular basis.
Oncology: Emetic Potential
Low (10% to 30%)
Oncology: Vesicant
May be an irritant
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Injection, powder for reconstitution:
Docefrez™: 20 mg, 80 mg [contains ethanol (in diluent), polysorbate 80 (in diluent); supplied with diluent]
Injection, solution: 10 mg/mL (2 mL, 8 mL, 16 mL)
Injection, solution [concentrate]:
Taxotere®: 20 mg/mL (1 mL, 4 mL) [contains dehydrated ethanol 0.395 g/mL, polysorbate 80]
Taxotere®: 20 mg/0.5 mL (0.5 mL [DSC], 2 mL [DSC]) [contains ethanol (in diluent), polysorbate 80]
References
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Ajani JA, Moiseyenko VM, Tjulandin S, et al, “Clinical Benefit With Docetaxel Plus Fluorouracil and Cisplatin Compared With Cisplatin and Fluorouracil in a Phase III Trial of Advanced Gastric or Gastroesophageal Cancer Adenocarcinoma: The V-325 Study Group,” J Clin Oncol, 2007, 25(22):3205-9.
Blohmer JU, Schmid P, Hilfrich J, et al, “Epirubicin and Cyclophosphamide Versus Epirubicin and Docetaxel as First-Line Therapy for Women With Metastatic Breast Cancer: Final Results of a Randomised Phase III Trial,” Ann Oncol, 2010, 21(7):1430-5.
Burstein HJ, Manola J, Younger J, et al, “Docetaxel Administered on a Weekly Basis for Metastatic Breast Cancer,” J Clin Oncol, 2000, 18(6):1212-9.
Esteva FJ, Valero V, Booser D, et al, “Phase II Study of Weekly Docetaxel and Trastuzumab for Patients With HER-2-Overexpressing Metastatic Breast Cancer,” J Clin Oncol, 2002, 20(7):1800-8.
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Floyd JD, Nguyen DT, Lobins RL, et al, “Cardiotoxicity of Cancer Therapy,” J Clin Oncol, 2005, 23(30):7685-96.
Garcia AA, Blessing JA, Vaccarell L, et al, “Phase II Clinical Trial of Docetaxel in Refractory Squamous Cell Carcinoma of the Cervix: A Gynecologic Oncology Group Study,” Am J Clin Oncol, 2007, 30(4):428-31.
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Janus N, Thariat J, Boulanger H, et al, “Proposal for Dosage Adjustment and Timing of Chemotherapy in Hemodialyzed Patients,” Ann Oncol, 2010, 21(7):1395-403.
Kushner DM, Connor JP, Sanchez F, et al, “Weekly Docetaxel and Carboplatin for Recurrent Ovarian and Peritoneal Cancer: A Phase II Study,” Gynecol Oncol, 2007, 105(2):358-64.
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Li YF, Fu S, Hu W, et al, “Systemic Anticancer Therapy in Gynecological Cancer Patients With Renal Dysfunction,” Int J Gynecol Cancer, 2007, 7(4):739-63.
Maki RG, Wathen JK, Patel SR, et al, “Randomized Phase II Study of Gemcitabine and Docetaxel Compared With Gemcitabine Alone in Patients With Metastatic Soft Tissue Sarcomas: Results of Sarcoma Alliance for Research Through Collaboration Study 002,” J Clin Oncol, 2007, 25(19):2755-63.
Markman M, Kennedy A, Webster K, et al, “Combination Chemotherapy With Carboplatin and Docetaxel in the Treatment of Cancers of the Ovary and Fallopian Tube and Primary Carcinoma of the Peritoneum,” J Clin Oncol, 2001, 19(7):1901-5.
Mavroudis D, Papakotoulas P, Ardavanis A, et al, “Randomized Phase III Trial Comparing Docetaxel Plus Epirubicin Versus Docetaxel Plus Capecitabine as First-Line Treatment in Women With Advanced Breast Cancer,” Ann Oncol, 2010, 21(1):48-54.
McCaffrey JA, Hilton S, Mazumdar M, et al, “Phase II Trial of Docetaxel in Patients With Advanced or Metastatic Transitional-Cell Carcinoma,” J Clin Oncol, 1997, 15(5):1853-7.
Morgan C, Tillett T, Braybrooke J, et al, “Management of Uncommon Chemotherapy-Induced Emergencies,” Lancet Oncol, 2011, 12(8):806-14.
Muro K, Hamaguchi T, Ohtsu A, et al, “A Phase II Study of Single-Agent Docetaxel in Patients With Metastatic Esophageal Cancer,” Ann Oncol, 2004, 15(6):955-9.
Navid F, Willert JR, McCarville MB, et al, “Combination of Gemcitabine and Docetaxel in the Treatment of Children and Young Adults With Refractory Bone Sarcoma,” Cancer, 2008, 113(2):419-25.
Pointreau Y, Garaud P, Chapet S, et al, “Randomized Trial of Induction Chemotherapy With Cisplatin and 5-Fluorouracil With or Without Docetaxel forLlarynx Preservation,” J Natl Cancer Inst, 2009, 101(7):498-506.
Posner MR, Glisson B, Frenette G, et al, “Multicenter Phase I-II Trial of Docetaxel, Cisplatin, and Fluorouracil Induction Chemotherapy for Patients With Locally Advanced Squamous Cell Cancer of the Head and Neck,” J Clin Oncol, 2001, 19(4):1096-104.
Posner MR, Hershock DM, Blajman CR, et al, “Cisplatin and Fluorouracil Alone or With Docetaxel in Head and Neck Cancer,” N Engl J Med, 2007, 357(17):1705-15.
Pouessel D, Culine S, Becht C, eneurosensory symptoms, gastrointestinal toxicity (eg, diarrhea, stomatitis), cutaneous reactions, fluid retention, epiphora, and canalicular stenosis neurosensory symptoms, gastrointestinal toxicity (eg, diarrhea, stomatitis), cutaneous reactions, fluid retention, epiphora, and canalicular stenosis t al, “Gemcitabine and Docetaxel as Front-Line Chemotherapy in Patients With Carcinoma of an Unknown Primary Site,” Cancer, 2004, 100(6):1257-61.
Schrijvers D, Van Herpen C, Kerger J, et al, “Docetaxel, Cisplatin and 5-Fluorouracil in Patients With Locally Advanced Unresectable Head and Neck Cancer: A Phase I-II Feasibility Study,” Ann Oncol, 2004, 15(4):638-45.
Smyth JF, Smith IE, Sessa C, et al, “Activity of Docetaxel (Taxotere) in Small Cell Lung Cancer. The Early Clinical Trials Group of the EORTC,” Eur J Cancer, 1994, 30A(8):1058-60.
Van Cutsem E, Moiseyenko VM, Tjulandin S, et al, “Phase III Study of Docetaxel and Cisplatin Plus Fluorouracil Compared With Cisplatin and Fluorouracil as First-Line Therapy for Advanced Gastric Cancer: A Report of the V325 Study Group,” J Clin Oncol, 2006, 24(31):4991-7.
Vasey PA, Jayson GC, Gordon A, et al, “Phase III Randomized Trial of Docetaxel-Carboplatin Versus Paclitaxel-Carboplatin as First-line Chemotherapy for Ovarian Carcinoma,” J Natl Cancer Inst, 2004, 96(22):1682-91.
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International Brand Names
Lexi-Comp.com
Last full review/revision February 2012
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