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DOCETAXEL

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Docetaxel, a microtubule inhibitor, belongs to the taxane class and is prepared by semi-synthesis with a precursor extracted from yew needles.

Specific Substances

    1) Docetaxolum
    2) NSC 628503
    3) RP-56976
    4) CAS 114977-28-5 (anhydrous docetaxel)
    5) CAS 148408-66-6 (docetaxel trihydrate)
    1.2.1) MOLECULAR FORMULA
    1) C(43)H(53)NO(14)-3H(2)O (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010)

Available Forms Sources

    A) FORMS
    1) Available in a sterile, single dose 80- or 20-mg (80 mg/4 mL and 20 mg/mL) injection concentrate vials (Prod Info TAXOTERE intravenous injection concentrate, 2015).
    B) USES
    1) Docetaxel is used in the treatment of breast cancer (single agent for locally advanced or metastatic breast cancer), non-small cell lung cancer (NSCLC) (single agent for locally advanced or metastatic NSCLC after platinum therapy failure), hormone refractory prostate cancer, gastric adenocarcinoma (GC) (combined with cisplatin and fluorouracil for untreated advanced GC) and squamous cell carcinoma of the head and neck cancer (SCCHN) (combined with cisplatin and fluorouracil for induction treatment of locally advanced SCCHN) (Prod Info TAXOTERE intravenous injection concentrate, 2015).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Docetaxel is indicated for the treatment of the following as a single agent or in combination with other chemotherapeutic agents: breast, lung and prostate cancers and gastric adenocarcinoma.
    B) PHARMACOLOGY: Docetaxel, a microtubule inhibitor, binds to tubulin and promotes its assembly into microtubules while inhibiting disassembly. The stabilization that occurs produces inhibition of mitotic and interphase cellular functions.
    C) TOXICOLOGY: Docetaxel inhibits normal interphase and mitotic cellular function, causing cell death. Overdose effects are seen primarily in rapidly dividing cells (ie, bone marrow, gastrointestinal tract).
    D) EPIDEMIOLOGY: Inadvertent exposure or overdose is rare.
    E) WITH THERAPEUTIC USE
    1) COMMON: Potentially serious events across all indications have included: infections, neutropenia, febrile neutropenia, fluid retention, anemia, thrombocytopenia, hypersensitivity, nausea, vomiting, diarrhea, liver function abnormalities, and mucositis and/or stomatitis. Patients with alterations in liver function are more likely to experience serious adverse events including death. Other common events observed with docetaxel include: fever, peripheral neuropathy, dysgeusia, dyspnea, constipation, anorexia, nail disorders, pain, skin reactions, motor dysfunction, myalgia, and alopecia. INFREQUENT: Cardiac dysrhythmias and hypotension are relatively uncommon with therapy.
    F) WITH POISONING/EXPOSURE
    1) OVERDOSE: Data are limited. Overdose effects are expected to be an extension of adverse events and include bone marrow suppression, peripheral neurotoxicity, and mucositis.
    2) MILD TO MODERATE TOXICITY: Early symptoms may include: nausea, vomiting and diarrhea.
    3) SEVERE TOXICITY: Myelosuppression (neutropenia and febrile neutropenia) is likely to develop and can be severe. Anemia and thrombocytopenia may develop. Other potentially serious events include: liver function impairment; fluid retention leading to edema, dyspnea, cardiac tamponade, or pleural effusion; and severe stomatitis. Patients with abnormal liver function are at increased risk of toxicity.
    0.2.20) REPRODUCTIVE
    A) Docetaxel is classified as FDA pregnancy category D. In animal studies, docetaxel was embryotoxic and fetotoxic. At the time of this review, no data were available to assess the potential effects of exposure to this agent during lactation in humans.
    0.2.21) CARCINOGENICITY
    A) There have been rare reports of acute myeloid leukemia in association with docetaxel therapy in combination with other chemotherapeutic agents and/or radiotherapy during postmarketing surveillance.

Laboratory Monitoring

    A) Obtain CBC with differential daily to evaluate for bone marrow suppression (primarily neutropenia). The median time to nadir was 7 days, while the median duration of severe neutropenia (less than 500 cells/mm(3)) was 7 days in therapeutic use. Serial counts should be monitored until patient recovery.
    B) Monitor for clinical evidence of infection, with particular attention to: odontogenic infection, oropharynx, esophagus, soft tissues particularly in the perirectal region, exit and tunnel sites of central venous access devices, upper and lower respiratory tracts, and urinary tract.
    C) Closely monitor liver enzymes, renal function, fluid status and electrolytes. Ensure adequate hydration and correct electrolyte abnormalities as needed.
    D) Monitor vital signs, including temperature.
    E) Obtain an ECG. Continuous cardiac monitoring is indicated in patients with evidence of conduction abnormalities.
    F) Clinically evaluate patients for the development of mucositis and/or peripheral neuropathy.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Docetaxel is only available parenterally; oral exposure is not anticipated. See the PARENTERAL EXPOSURE section for further information.
    0.4.6) PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is primarily symptomatic and supportive, there is no antidote. Early signs of toxicity may include nausea/vomiting and diarrhea. It may be necessary to treat with multiple concomitant agents, from different drug classes, in patients with persistent symptoms. BONE MARROW SUPPRESSION: Neutropenia should be anticipated. Colony stimulating factor (filgrastim or sargramostim) should be initiated as soon as possible after exposure. Place patients with severe neutropenia in protective isolation. PERIPHERAL NEUROPATHY: Likely to develop in overdose. Monitor and treat symptoms. Effects are usually reversible, but may persist for long periods. MYALGIAS: Initially treat with NSAIDs.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) NEUTROPENIA: Bone marrow suppression (ie, neutropenia) may be severe. Neutropenia is the dose-dependent and the dose-limiting toxicity in therapy. Colony stimulating factor (filgrastim or sargramostim) should be initiated as soon as possible. Patients with severe neutropenia should be in protective isolation. Platelet and red cell transfusions may be necessary. EMESIS: Aggressively treat with antiemetics and fluid and electrolyte replacement as indicated. Closely monitor patients for hypotension, bradycardia, and other cardiac dysrhythmias. Monitor liver enzymes and renal function.
    C) DECONTAMINATION
    1) PREHOSPITAL: Docetaxel is only available parenterally; oral exposure is unlikely.
    2) HOSPITAL: Activated charcoal and/or gastric lavage are not indicated since overdose most often occurs by the intravenous route.
    D) AIRWAY MANAGEMENT
    1) Consider orotracheal intubation in patients with significant CNS depression or respiratory failure.
    E) HYPERSENSITIVITY REACTION
    1) MILD/MODERATE: Antihistamines with or without inhaled beta agonists, corticosteroids or epinephrine. SEVERE: Oxygen, aggressive airway management, antihistamines, epinephrine, corticosteroids, ECG monitoring, and IV fluids.
    F) ANTIDOTE
    1) There is no known antidote for docetaxel overdose.
    G) MYELOSUPPRESSION
    1) Severe neutropenia should be anticipated following a significant exposure. Place patients in protective isolation. Give colony stimulating factor as soon as possible. Closely monitor CBC with differential daily until patient recovery. Filgrastim: 5 mcg/kg/day IV or subQ (preferred route). Sargramostim: 250 mcg/m(2)/day IV over 4 hours OR 250 mcg/m(2)/day SubQ once daily.
    H) NEUTROPENIA
    1) Prophylactic therapy with a fluoroquinolone should be considered in high risk patients with expected prolonged (more than 7 days), and profound neutropenia (ANC 100 cells/mm(3) or less).
    I) FEBRILE NEUTROPENIA
    1) If fever (38.3 C) develops during the neutropenic phase (ANC 500 cells/mm(3) or less), cultures should be obtained and empiric antibiotics started. HIGH RISK PATIENT (anticipated neutropenia of 7 days or more; unstable; significant comorbidities): IV monotherapy with either piperacillin-tazobactam; a carbapenem (meropenem or imipenem-cilastatin); or an antipseudomonal beta-lactam agent (eg, ceftazidime or cefepime). LOW RISK PATIENT (anticipated neutropenia of less than 7 days; clinically stable; no comorbidities): oral ciprofloxacin and amoxicillin/clavulanate.
    J) VOMITING
    1) Docetaxel has low emetogenic potential in therapeutic use. If nausea and vomiting develops, treat with high-dose dopamine (D2) receptor antagonists (eg, metoclopramide), phenothiazines (eg, promethazine or prochlorperazine), 5-HT3 serotonin antagonists (eg, ondansetron, dolasetron, or granisetron), benzodiazepines (eg, lorazepam), corticosteroids (eg, dexamethasone), and/or antipsychotics (eg, haloperidol). Diphenhydramine may be required to prevent dystonic reactions from dopamine antagonists, phenothiazines, or antipsychotics. Replace fluid and electrolytes as needed. Monitor liver enzymes and renal function closely.
    K) DIARRHEA
    1) For mild to moderate diarrhea without signs of infection, treat with loperamide 2 mg every 4 hours for 24 hours. Patients with severe, uncontrolled diarrhea should be treated with octreotide, aggressive IV fluid management, and antibiotics. Monitor electrolytes as indicated.
    L) STOMATITIS
    1) Ice chips (ie, cryotherapy) may help minimize symptoms. Treat mild symptoms of pain or xerostomia with bland rinses (ie, normal saline or sodium bicarbonate). Treat salivary gland dysfunction or xerostomia with sugarless candy/mints, pilocarpine/cevimeline, bethanechol, topical fluorides or remineralizing agents. Treat moderate pain symptoms with topical anesthetics (ie, lidocaine, benzocaine, dyclonine, diphenhydramine, or doxepin) and mucosal coating agents (benzydamine) as needed. Moderate to severe symptoms may require systemic analgesics. Prophylactic treatment to prevent infection is suggested; topical or systemic treatment may be indicated. Palifermin, a keratinocyte growth factor, is indicated to reduce the incidence and duration of severe oral mucositis in patients with hematologic malignancies receiving myelotoxic therapy requiring hematopoietic stem cell support. In patients with severe docetaxel overdose, administer palifermin 60 mcg/kg/day IV bolus injection starting 24 hours after the overdose for 3 consecutive days.
    M) PERIPHERAL NEUROTOXICITY
    1) Peripheral neurotoxicity should be anticipated in overdose. Monitor and treat symptoms as indicated.
    N) EXTRAVASATION INJURY
    1) Events are usually mild with docetaxel. If extravasation occurs, stop the infusion. Disconnect the IV tubing, but leave the cannula or needle in place. Attempt to aspirate the extravasated drug from the needle or cannula. If possible, withdraw 3 to 5 mL of blood and/or fluids through the needle/cannula. Several cases have reported the use of either warm compresses/soaks (for 15 to 20 minutes at least 4 times daily for 1 to 2 days) or local cooling (ice packs can be applied for 15 to 20 minutes at least 4 times daily). Elevate the affected area. Apply a warm or cold compress as indicated (see below). Administer analgesia for severe pain. If pain persists, there is concern for compartment syndrome, or injury is apparent, an early surgical consult should be considered. Close observation of the extravasated area is suggested. If tissue sloughing, necrosis or blistering occurs, treat as a chemical burn (ie, antiseptic dressings, silver sulfadiazine, antibiotics when applicable). Surgical or enzymatic debridement may be required. Risk of infection is increased in chemotherapy patients with reduced neutrophil count following extravasation. Consider culturing any open wounds. Monitor the site for the development of cellulitis, which may require antibiotic therapy.
    O) INTRATHECAL INJECTION
    1) No clinical reports available, information derived from experience with other antineoplastics. Keep patient upright if possible. Immediately drain at least 20 mL CSF; drainage of up to 70 mL has been tolerated in adults. Follow with CSF exchange (remove serial 20 mL aliquots CSF and replace with equivalent volumes of warmed, preservative free normal saline or lactated ringers). Consult a neurosurgeon for placement of a ventricular catheter and begin ventriculolumbar perfusion (infuse warmed preservative free normal saline or lactated ringers through ventricular catheter, drain fluid from lumbar catheter; typical volumes 80 to 150 mL/hr for 18 to 24 hr). FFP (25 mL FFP/liter NS or LR) or albumin 5% have also been used for perfusion; may be useful because of high protein binding of docetaxel. Dexamethasone 4 mg intravenously every 6 hours to prevent arachnoiditis.
    P) ENHANCED ELIMINATION
    1) Docetaxel is highly protein bound with a large volume of distribution. It is not anticipated that enhanced elimination would be beneficial following overdose.
    Q) PATIENT DISPOSITION
    1) HOME CRITERIA: There is no data to support home management. Patients with a docetaxel overdose need to be admitted.
    2) ADMISSION CRITERIA: Patients should be closely monitored in an inpatient setting, with frequent monitoring of vital signs (every 4 hours for the first 24 hours), daily monitoring of CBC with differential until bone marrow suppression is resolved, along with monitoring of serum electrolytes, renal function, and hepatic enzymes.
    3) CONSULT CRITERIA: Consult an oncologist, medical toxicologist and/or poison center for assistance in managing patients with a docetaxel overdose.
    4) TRANSFER CRITERIA: Patients with severe overdose or profound neutropenia may benefit from a transfer to a bone marrow transplant or cancer treatment center.
    R) PITFALLS
    1) Symptoms in patients may be delayed (particularly myelosuppression), so reliable follow-up is imperative. Patients taking these medications may have severe comorbidities and access to other drugs with significant toxicity.
    S) PHARMACOKINETICS
    1) Docetaxel is highly protein bound (94%) and has a mean steady state volume of distribution of 113 L. It is metabolized by the CYP3A4 isoenzyme. Docetaxel is eliminated in the feces (approximately 75%) and urine (approximately 6%) following oxidative metabolism. In one study, approximately 80% of docetaxel was recovered in the feces during the first 48 hours as 1 major and 3 minor metabolites.
    T) DIFFERENTIAL DIAGNOSIS
    1) Differential diagnosis includes other chemotherapeutic agents.

Range Of Toxicity

    A) TOXICITY: Limited data. In 2 cases, severe neutropenia, mild asthenia, cutaneous reactions, and mild paresthesia occurred in both patients following a 150 mg/m(2) and a 200 mg/m(2) infusion. Both recovered with supportive care.
    B) THERAPEUTIC DOSE: ADULT: The recommended dose is 60 mg/m(2) to 100 mg/m(2) IV over 1 hour every 3 weeks for various disease states. PEDIATRIC: The safety and efficacy of docetaxel have not been established in pediatric patients.

Clinical Effects

Summary Of Exposure

    A) USES: Docetaxel is indicated for the treatment of the following as a single agent or in combination with other chemotherapeutic agents: breast, lung and prostate cancers and gastric adenocarcinoma.
    B) PHARMACOLOGY: Docetaxel, a microtubule inhibitor, binds to tubulin and promotes its assembly into microtubules while inhibiting disassembly. The stabilization that occurs produces inhibition of mitotic and interphase cellular functions.
    C) TOXICOLOGY: Docetaxel inhibits normal interphase and mitotic cellular function, causing cell death. Overdose effects are seen primarily in rapidly dividing cells (ie, bone marrow, gastrointestinal tract).
    D) EPIDEMIOLOGY: Inadvertent exposure or overdose is rare.
    E) WITH THERAPEUTIC USE
    1) COMMON: Potentially serious events across all indications have included: infections, neutropenia, febrile neutropenia, fluid retention, anemia, thrombocytopenia, hypersensitivity, nausea, vomiting, diarrhea, liver function abnormalities, and mucositis and/or stomatitis. Patients with alterations in liver function are more likely to experience serious adverse events including death. Other common events observed with docetaxel include: fever, peripheral neuropathy, dysgeusia, dyspnea, constipation, anorexia, nail disorders, pain, skin reactions, motor dysfunction, myalgia, and alopecia. INFREQUENT: Cardiac dysrhythmias and hypotension are relatively uncommon with therapy.
    F) WITH POISONING/EXPOSURE
    1) OVERDOSE: Data are limited. Overdose effects are expected to be an extension of adverse events and include bone marrow suppression, peripheral neurotoxicity, and mucositis.
    2) MILD TO MODERATE TOXICITY: Early symptoms may include: nausea, vomiting and diarrhea.
    3) SEVERE TOXICITY: Myelosuppression (neutropenia and febrile neutropenia) is likely to develop and can be severe. Anemia and thrombocytopenia may develop. Other potentially serious events include: liver function impairment; fluid retention leading to edema, dyspnea, cardiac tamponade, or pleural effusion; and severe stomatitis. Patients with abnormal liver function are at increased risk of toxicity.

Vital Signs

    3.3.3) TEMPERATURE
    A) Fever without infection has been reported with docetaxel therapy (Prod Info TAXOTERE(R) IV injection, 2010).

Heent

    3.4.3) EYES
    A) GLAUCOMA
    1) CASE REPORT: A 31-year-old woman developed visual loss and wide angle glaucoma after the fifth cycle of docetaxel. Glaucoma recurred in the third cycle after she was switched to paclitaxel. Both times glaucoma developed after the onset of diffuse fluid retention (Fabre-Guillevin et al, 1999).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) VENTRICULAR ARRHYTHMIA
    1) WITH THERAPEUTIC USE
    a) Severe dysrhythmias have been reported infrequently with docetaxel therapy (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).
    B) CONGESTIVE HEART FAILURE
    1) WITH THERAPEUTIC USE
    a) In a study, deterioration of 10% or more in left ventricular ejection fraction developed in 8.1% of patients receiving docetaxel 100 mg/m(2) for breast cancer who had serial assessments of left ventricular ejection fraction (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).
    C) HYPOTENSIVE EPISODE
    1) WITH THERAPEUTIC USE
    a) Hypotension developed in 2.8% of patients with solid tumors receiving docetaxel; more than half of the patients required no treatment (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) INTERSTITIAL PNEUMONIA
    1) WITH THERAPEUTIC USE
    a) SUMMARY: Interstitial pneumonitis has developed with docetaxel therapy when administered alone or combination with other chemotherapies. High dose corticosteroid therapy was beneficial in some cases; however, fatalities have occurred despite aggressive treatment (Kuip & Muller, 2009; Leimgruber et al, 2006; Mileshkin et al, 2001; Wang et al, 2001).
    b) CASE REPORT: A fatal case of pneumonitis was reported in a 63-year-old woman with locally advanced breast cancer who received 2 courses of docetaxel and trastuzumab (100 mg/m(2) and 6 mg/kg, respectively, once every 3 weeks). The patient presented with fever (39.4 degrees C), chills, and minimal dyspnea one week after the first course of treatment. She recovered with IV ceftazidime. Six days after receiving a second course of docetaxel and trastuzumab with prophylactic ciprofloxacin, the patient presented with fever, chills, and dyspnea. A chest x-ray was normal. Fever and dyspnea responded to antibiotics and the patient was discharged. Four days later, the patient was readmitted with fever (40.1 degrees C), dyspnea, and dry cough. A thoracic CT scan performed 2 days later revealed multiple consolidations in the peripheral of both lungs and ground glass aspect of lungs, consistent with lung inflammation and/or edema. Fever responded to prednisone, but respiratory status continued to worsen therapy. The patient died immediately upon discontinuation of treatment. Diffuse alveolar damage, interstitial inflammation (both lungs), and pneumonic consolidations (right lung) were identified during postmortem histological examination (Kuip & Muller, 2009).
    c) CASE REPORT: A 72-year-old man with hormone-refractory prostate cancer developed subacute interstitial pneumonitis after receiving 7 cycles of docetaxel (30 mg/m(2) over 1 hour, repeated weekly; accumulating dose, 420 mg). A blood gas analysis showed a pH of 7.465, pCO2 36.2 mmHg, and pO2 59.7 mmHg. Chest radiograph revealed diffuse bilateral interstitial infiltrates with confluence in mid to upper lungs. Despite supportive care and high-dose corticosteroid treatment, he died of multiple organ failure 39 days after admission. Postmortem examination of the lung revealed thickening of the alveolar walls by fibrosis and interstitial inflammation (Leimgruber et al, 2006).
    d) CASE REPORTS: Severe, life-threatening interstitial pneumonitis occurred following high-dose cyclophosphamide, thiotepa, and docetaxel with stem cell rescue in 2 patients with metastatic breast cancer. Both female patients (ages, 41 and 48 years) received 2 cycles of docetaxel 100 mg/m(2) prior to high-dose chemotherapy, the second followed by filgrastim 10 mcg/kg/day subcutaneously for mobilization of peripheral blood progenitor cells (PBPCs). High-dose chemotherapy was then administered consisting of cyclophosphamide 4 g/m(2), thiotepa 350 mg/m(2), and docetaxel 125 mg/m(2). Fever, dyspnea, and a dry cough developed in both patients. Bronchoscopy demonstrated inflammatory infiltrate that was consistent with drug-induced interstitial pneumonitis. Both patients improved with steroid therapy (Mileshkin et al, 2001).
    B) EXTRINSIC ALLERGIC ALVEOLITIS
    1) WITH THERAPEUTIC USE
    a) CASE REPORTS: Hypersensitivity pneumonitis and respiratory failure developed in 4 patients with advanced non-small cell lung cancer after 1 to 6 courses of docetaxel therapy. Pneumonitis occurred in a 44-year-old woman 5 days following the first course of docetaxel 33 mg/m(2), or total of 44 mg. In the other 3 cases, pneumonitis developed after 6 courses of docetaxel 30 mg/m(2) in 73- and 70-year-old men (cumulative dose of 644.4 mg and 612 mg, respectively), and 2 weeks after the second docetaxel 60 mg/m(2) course in a 75-year-old man. The patients presented with dyspnea and rapid progression to respiratory failure requiring mechanical ventilation. Hypersensitivity pneumonitis was diagnosed based upon radiographic findings of diffuse interstitial infiltrates, rapid clinical progression, poor responsiveness to broad-spectrum antibiotics, and the exclusion of other causative factors, including metastatic disease, connective lung disease, infection, or radiation lung damage. The patients received IV hydrocortisone 1200 mg/day or methylprednisolone 240 mg/day. Transient improvement occurred in 2 patients, but deterioration developed during tapering of the corticosteroid. All 4 patients died from persistent hypersensitivity pneumonitis complicated by such events as infection, multiorgan failure, and pneumothorax (Wang et al, 2001).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) NEUROPATHY
    1) WITH THERAPEUTIC USE
    a) In metastatic breast cancer patients, severe neurosensory symptoms (paresthesia, dysesthesia, pain) occurred in 5.5% (53 of 965) of patients. The discontinuation rate was 6.1%. The typical time to spontaneous resolution was a median of 9 weeks (range 0 to 106 weeks) in patients for whom follow-up data were available. Severe peripheral motor neuropathy, primarily characterized by distal extremity weakness, was experienced in 4.4% (42 of 965) of patients (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).
    B) ASTHENIA
    1) WITH THERAPEUTIC USE
    a) Patients experienced asthenia, which was possibly or probably related to docetaxel 100 mg/m(2) every 3 weeks (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).
    b) In a multicenter, open-label, randomized trial in which 1480 patients with axillary-node-positive breast cancer and no evidence of distant metastatic disease received either adjuvant treatment with docetaxel 75 mg/m(2) administered 1 hour after doxorubicin 50 mg/m(2) and cyclophosphamide 500 mg/m(2) (docetaxel arm; n=744) or doxorubicin 50 mg/m(2) followed by fluorouracil 500 mg/m(2) and cyclophosphamide 500 mg/m(2) (control arm; n=736), asthenia was reported in 81% of the docetaxel arm compared with 71% of the control arm (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).
    C) ALCOHOL INTOXICATION
    1) WITH THERAPEUTIC USE
    a) CASE SERIES: In a small study of outpatients treated with paclitaxel (n=36) or docetaxel (n=16), 5 patients reported a "drunken sensation" after receiving the paclitaxel infusion. Both paclitaxel and docetaxel contain ethanol as a diluent. Blood alcohol concentrations measured by breathalyzer after infusion were noted to be greater than 0.15 mg/L in 20 patients treated with paclitaxel. No significant blood alcohol concentrations were noted with docetaxel (Komagata et al, 2005).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) DIARRHEA
    1) WITH THERAPEUTIC USE
    a) Diarrhea can commonly occur with docetaxel therapy (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).
    B) NAUSEA AND VOMITING
    1) WITH THERAPEUTIC USE
    a) Nausea and vomiting can commonly occur with docetaxel therapy (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).
    C) STOMATITIS
    1) WITH THERAPEUTIC USE
    a) SUMMARY: Stomatitis is relatively common and is probably related to docetaxel doses of 100 mg/m(2) every 3 weeks. Severe stomatitis developed in 5.5% to 7.4% of 92 breast cancer patients receiving docetaxel; pretreatment with corticosteroids decreased this to 1.1% (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).
    b) In a multicenter, open-label, randomized trial in which 1480 patients with axillary-node-positive breast cancer and no evidence of distant metastatic disease received either adjuvant treatment of docetaxel 75 mg/m(2) administered 1 hour after doxorubicin 50 mg/m(2) and cyclophosphamide 500 mg/m(2) (docetaxel arm; n=744) or doxorubicin 50 mg/m(2) followed by fluorouracil 500 mg/m(2) and cyclophosphamide 500 mg/m(2) (control arm; n=736), stomatitis (all grades) was reported in 69% of the docetaxel arm compared with 53% of the control arm. Grade 3 to 4 stomatitis was reported in 7% and 2%, respectively (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).
    c) In a multicenter, open-label, randomized trial in which 355 patients with inoperable, locally advanced squamous cell carcinoma of the head and neck (ie, WHO performance status 0 or 1) received either docetaxel 75 mg/m(2) followed by cisplatin 75 mg/m(2) on day 1, followed by fluorouracil 750 mg/m(2) per day as a continuous infusion on days 1 to 5 with cycles repeated every three weeks for 4 cycles (docetaxel arm; n=174) or cisplatin 100 mg/m(2) on day 1, followed by fluorouracil 1000 mg/m(2)/day as a continuous infusion on days 1 to 5 without docetaxel (control arm; n=181), stomatitis was reported in 43% of the docetaxel arm compared with 47% of the control arm (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) LIVER ENZYMES ABNORMAL
    1) WITH THERAPEUTIC USE
    a) There have been infrequent reports of liver enzyme abnormalities during docetaxel therapy. However, patients who have increased bilirubin and liver enzyme concentrations are at an increased risk of developing severe complications (ie, neutropenia , infections and severe thrombocytopenia) (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).
    B) HEPATIC COMA
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: A 42-year-old man with metastatic lung cancer to the brain developed hepatic coma after receiving docetaxel and carboplatin. His liver enzyme and serum ammonia concentrations were elevated one day after chemotherapy; a neomycin enema and lactulose decreased the ammonia level and resulted in resolution of symptoms (Chen et al, 2001).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) ACUTE RENAL FAILURE SYNDROME
    1) WITH THERAPEUTIC USE
    a) During postmarketing surveillance, renal failure has been reported in patients who received treatment with docetaxel. Most cases were associated with concomitant nephrotoxic drug use (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) NEUTROPENIA
    1) WITH THERAPEUTIC USE
    a) Neutropenia has been the primary dose-limiting toxic effect of docetaxel therapy. Events may be severe resulting in infection (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).
    B) ANEMIA
    1) WITH THERAPEUTIC USE
    a) Anemia has been commonly reported with docetaxel use, but severe events generally do not occur (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).
    b) INCIDENCE: Anemia was reported in 89% to 91% of patients during multicenter, open-label randomized trials; grade 3 to 4 anemia occurred in 4% to 9% of patients (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).
    c) In a multicenter, open-label, randomized trial in which 1480 patients with axillary-node-positive breast cancer and no evidence of distant metastatic disease received either adjuvant treatment of docetaxel 75 mg/m(2) administered 1 hour after doxorubicin 50 mg/m(2) and cyclophosphamide 500 mg/m(2) (docetaxel arm; n=744) or doxorubicin 50 mg/m(2) followed by fluorouracil 500 mg/m(2) and cyclophosphamide 500 mg/m(2) (control arm; n=736), grade 3 to 4 anemia was reported in 4% of the docetaxel arm compared with 2% of the control arm (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).
    d) In a multicenter, open-label, randomized trial in which 355 patients with inoperable, locally advanced squamous cell carcinoma of the head and neck (ie, WHO performance status 0 or 1) received either docetaxel 75 mg/m(2) followed by cisplatin 750 mg/m(2) on day 1, followed by fluorouracil 750 mg/m(2) per day as a continuous infusion on days 1 to 5 with cycles repeated every 3 weeks for 4 cycles (docetaxel arm; n=174) or the same regimen of cisplatin and fluorouracil without docetaxel (control arm; n=181), grade 3 to 4 anemia was reported in 9% of the docetaxel arm compared with 14% of the control arm (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).
    C) FEBRILE NEUTROPENIA
    1) WITH THERAPEUTIC USE
    a) SUMMARY: Febrile neutropenia is relatively common and appears to be dose related with a frequency of 12% in patients administered 100 mg/m(2). It is unlikely to occur in patients administered 60 mg/m(2). Patients with an increased bilirubin or elevated alkaline phosphatase were more likely to develop febrile neutropenia, grade 4 neutropenia and severe thrombocytopenia and toxic death. An elevated transaminase concentration of greater that 1.5 the upper limit of normal was also associated with a higher rate of grade 4 febrile neutropenia (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).
    b) In a multicenter, open-label, randomized trial in which 1480 patients with axillary-node-positive breast cancer and no evidence of distant metastatic disease received either adjuvant treatment with docetaxel 75 mg/m(2) administered 1 hour after doxorubicin 50 mg/m(2) and cyclophosphamide 500 mg/m(2) (docetaxel arm; n=744) or doxorubicin 50 mg/m(2) followed by fluorouracil 500 mg/m(2) and cyclophosphamide 500 mg/m(2) (control arm; n=736), febrile neutropenia was reported in 25% of the docetaxel arm compared with 3% of the control arm (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).
    c) In a multicenter, open-label, randomized trial in which 355 patients with inoperable, locally advanced squamous cell carcinoma of the head and neck (ie, WHO performance status 0 or 1) received either docetaxel 75 mg/m(2) followed by cisplatin 75 mg/m(2) on day 1, followed by fluorouracil 750 mg/m(2) per day as a continuous infusion on days 1 to 5 with cycles repeated every 3 weeks for 4 cycles (docetaxel arm; n=174) or cisplatin 100 mg/m(2) on day 1, followed by fluorouracil 1000 mg/m(2)/day as a continuous infusion on days 1 to 5 without docetaxel (control arm; n=181), febrile neutropenia (grade 2 or more fever and grade 4 neutropenia requiring IV antibiotics and/or hospitalization) was reported in 5% of the docetaxel arm compared with 2% of the control arm (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).
    D) THROMBOCYTOPENIC DISORDER
    1) WITH THERAPEUTIC USE
    a) Thrombocytopenia (less than 100,000 cells/mm(3)) may occur with docetaxel therapy. In a summary of all patients (n=2045) with all tumor types receiving docetaxel at doses of 100 mg/m(2), 8% of patients developed thrombocytopenia (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).
    E) LYMPHOCYTOPENIA
    1) WITH THERAPEUTIC USE
    a) Reversible lymphopenia has been reported after docetaxel use in patients with solid tumors (Kotsakis et al, 2000).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) ALOPECIA
    1) WITH THERAPEUTIC USE
    a) Alopecia has been reported commonly with docetaxel therapy in patients with various tumor types, including patients with breast cancer (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010):
    B) ERUPTION
    1) WITH THERAPEUTIC USE
    a) Fixed drug eruptions have been reported with docetaxel therapy (Baykal et al, 2000; Chu et al, 2000).
    C) EXTRAVASATION INJURY
    1) WITH THERAPEUTIC USE
    a) Docetaxel extravasation was associated with erythema (or darkened pigmentation in 1 black patient), swelling, and pain or tenderness within one week of intravenous administration in a series of 4 patients. Blisters developed in 2 of the 4 patients and desquamation occurred within 3 weeks in all 4 patients. Following supportive care, resolution of signs and symptoms and regeneration of epidermis occurred within 3 weeks. Residual changes in skin pigmentation persisted in 2 patients and mildly decreased sensation of the affected extremity persisted in 1 patient 18 months after injury (Ascherman et al, 2000).
    b) CASE REPORT: A 71-year-old woman developed a grade IV local skin reaction after treatment with docetaxel and carboplatin. After receiving 100 mL of docetaxel (0.48 mg per mL normal saline), an infiltration into the dorsum of the left hand was observed. The infusion was stopped immediately; no apparent abnormalities were noted. Six days later, the patient noticed a red area on the dorsum of her left hand and applied a hot pack to the area. The following day, severe pain and edema developed that were treated with cephalexin 500 mg 4 times daily for 10 days. A few days later, she presented with a 12 by 10 cm area of deep purple discoloration, edema, and blistering on the dorsum of her left hand. The lesion was painful and limited her range of motion. Blistering and desquamation of the entire dorsum of her left hand occurred over the next 4 weeks. Conservative management with NSAID agents, mild opioids, and physical therapy resulted in full return of function over 4 weeks (Raley et al, 2000).
    D) ERYTHEMA
    1) WITH THERAPEUTIC USE
    a) Localized erythema of the extremities with edema followed by desquamation has been reported (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).
    E) NAIL FINDING
    1) WITH THERAPEUTIC USE
    a) Severe nail disorders including hypo- or hyperpigmentation, onycholysis, and pain occur rarely in patients receiving docetaxel (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).
    F) ACRAL ERYTHEMA DUE TO CYTOTOXIC THERAPY
    1) WITH THERAPEUTIC USE
    a) Severe hand and foot syndrome (acral erythema) has been associated with docetaxel therapy in published literature and postmarketing surveillance, although the incidence has not been defined (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010; Farhat et al, 2008; Prod Info TAXOTERE(R) IV injection, 2006; Nagore et al, 2000).
    b) BACKGROUND: Palmar plantar erythrodysesthesia (PPE) (hand-foot syndrome), which is characterized as paresthesia leading to painful erythema on the palms and soles, is a relatively frequent toxic reaction related to some chemotherapy agents (ie, doxorubicin, cytarabine and fluorouracil). Docetaxel has been reported to induce PPE although the incidence has not been defined in the published literature. In a study of patients receiving docetaxel 100 mg/m(2)/day as either a 2 or 3 hour infusion every 21 days, the incidence of PPE was 58%, with an onset of 2 to 4 days. Weekly administration of docetaxel may be associated with fewer episodes of PPE (Nagore et al, 2000).
    c) In 5 case reports of female patients with breast cancer, hand-foot syndrome (HFS) developed 2 to 7 days following single-cycle or multiple cycles of docetaxel and resolved within 1 to 2 weeks of docetaxel discontinuation. Patients were all treated with docetaxel 100 mg/m(2) doses in different combinations of chemotherapy: preceded by doxorubicin/cyclophosphamide/paclitaxel, or fluorouracil/epirubicin/cyclophosphamide, given as monotherapy, with or without filgrastim, but without pegylated granulocyte colony-stimulating factor. Patients presented with signs and symptoms including itching, burning, edema, erythema, and desquamation of the hands, face, feet, and neck. Pathological examination in one patient revealed focal parakeratosis in the epidermis with mild spongiosis, scattered dyskeratosis, squamation of the epithelial cells and maturation disarray, and dermal changes including edema, blood vessel dilation, perivascular and interstitial lymphocytic inflammatory cell infiltrate, neutrophils and nuclear debris. HFS lesions were severe and resulted in all 5 patients discontinuing docetaxel therapy. Palliative treatments included emollient creams, systemic steroids, and pyridoxine 150 mg/day for 2 weeks. Following the discontinuation of docetaxel, lesions resolved within 1 to 2 weeks with no sequelae (Farhat et al, 2008).
    G) ERYTHEMA MULTIFORME
    1) WITH THERAPEUTIC USE
    a) During postmarketing surveillance, erythema multiforme has been reported in patients who received treatment with docetaxel (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) MUSCLE PAIN
    1) WITH THERAPEUTIC USE
    a) Arthralgia and/or myalgia have been reported with docetaxel therapy (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) ANAPHYLACTOID REACTION
    1) WITH THERAPEUTIC USE
    a) Type I hypersensitivity reactions, including anaphylaxis, have been reported infrequently during infusion of docetaxel. These reactions are characterized by hypotension, dyspnea with or without bronchospasm, urticaria, erythematous rashes, and rare reports of fatalities have occurred (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).

Reproductive

    3.20.1) SUMMARY
    A) Docetaxel is classified as FDA pregnancy category D. In animal studies, docetaxel was embryotoxic and fetotoxic. At the time of this review, no data were available to assess the potential effects of exposure to this agent during lactation in humans.
    3.20.2) TERATOGENICITY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the teratogenic potential of docetaxel (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).
    B) LACK OF EFFECT
    1) In a systematic review, 92.3% of neonates were born healthy following second- or third-trimester exposure (gestational age range, 16 to 30 weeks) to 2 to 5 cycles of docetaxel- (n=1) or paclitaxel- (n=12) based chemotherapy during treatment for maternal ovarian cancer (n=11) or dysgerminoma (n=1). One postpartum death occurred in a 5-day-old docetaxel-exposed infant, which was attributed to congenital abnormalities diagnosed before chemotherapy initiation. One paclitaxel-exposed infant developed intrauterine growth restriction. All infants were born prematurely (mean gestational age, 37.5 weeks; range, 34 to 38 weeks) via cesarean section with a mean weight of 2381 g (range, 1900 to 2800 g). One paclitaxel case study with an 11-year followup found a case of attention deficit disorder in a pair of twins, while the remaining studies showed no long-term developmental effects (median followup, 20 months) (Zagouri et al, 2012).
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to docetaxel during pregnancy in humans (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).
    B) PREGNANCY CATEGORY
    1) Docetaxel is classified as FDA pregnancy category D (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).
    C) SYSTEMIC REVIEW
    1) In a systematic review, 92.3% of neonates were born healthy following second- or third-trimester exposure (gestational age range, 16 to 30 weeks) to 2 to 5 cycles of docetaxel- (n=1) or paclitaxel- (n=12) based chemotherapy during treatment for maternal ovarian cancer (n=11) or dysgerminoma (n=1). One paclitaxel-exposed infant developed intrauterine growth restriction. All infants were born prematurely (mean gestational age, 37.5 weeks; range, 34 to 38 weeks) via cesarean section with a mean weight of 2381 g (range, 1900 to 2800 g). One postpartum death occurred in a 5-day-old docetaxel-exposed infant, which was attributed to congenital abnormalities diagnosed before chemotherapy initiation. One paclitaxel case study with an 11-year followup found a case of attention deficit disorder in a pair of twins, while the remaining studies showed no long-term developmental effects (median followup, 20 months) (Zagouri et al, 2012).
    D) ANIMAL STUDIES
    1) RATS, RABBITS: Embryotoxicity, fetotoxicity (ie, intrauterine mortality, increased resorption, reduced fetal weight, and fetal ossification delay), and maternal toxicity were observed when rats and rabbits were given docetaxel at about 1/50 and 1/300 the daily maximum recommended human dose on a mg/m(2) basis, respectively, during the period of organogenesis (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to docetaxel during lactation in humans (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).

Carcinogenicity

    3.21.2) SUMMARY/HUMAN
    A) There have been rare reports of acute myeloid leukemia in association with docetaxel therapy in combination with other chemotherapeutic agents and/or radiotherapy during postmarketing surveillance.
    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) There have been rare reports of acute myeloid leukemia in association with docetaxel therapy in combination with other chemotherapeutic agents and/or radiotherapy during postmarketing surveillance (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).

Genotoxicity

    A) There was evidence of clastogenicity in the in vitro chromosome aberration test in CHO-K1 cells and in the in vivo micronucleus test in mice administered doses of 0.39 to 1.56 mg/kg (about 1/60th to 1/15th the recommended human dose on a mg/m(2) basis). There was no evidence of mutagenicity in the Ames test or the CHO/HGPRT gene mutation assay (Prod Info TAXOTERE(R) IV injection, 2010).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Obtain CBC with differential daily to evaluate for bone marrow suppression (primarily neutropenia). The median time to nadir was 7 days, while the median duration of severe neutropenia (less than 500 cells/mm(3)) was 7 days in therapeutic use. Serial counts should be monitored until patient recovery.
    B) Monitor for clinical evidence of infection, with particular attention to: odontogenic infection, oropharynx, esophagus, soft tissues particularly in the perirectal region, exit and tunnel sites of central venous access devices, upper and lower respiratory tracts, and urinary tract.
    C) Closely monitor liver enzymes, renal function, fluid status and electrolytes. Ensure adequate hydration and correct electrolyte abnormalities as needed.
    D) Monitor vital signs, including temperature.
    E) Obtain an ECG. Continuous cardiac monitoring is indicated in patients with evidence of conduction abnormalities.
    F) Clinically evaluate patients for the development of mucositis and/or peripheral neuropathy.
    4.1.2) SERUM/BLOOD
    A) HEMATOLOGIC
    1) Complete blood counts with differential and platelets should be monitored to evaluate for bone marrow suppression. Serial counts should be monitored until patient recovery.
    2) Based on therapeutic use, the median time to nadir was 7 days, while the median duration of severe neutropenia (less than 500 cells/mm(3)) was 7 days (Prod Info TAXOTERE(R) IV injection, 2010)
    B) BLOOD/SERUM CHEMISTRY
    1) Closely monitor fluid balance, electrolytes and liver enzymes.
    4.1.4) OTHER
    A) OTHER
    1) ECG
    a) Obtain an ECG. Continuous cardiac monitoring may be indicated in patients with evidence of conduction abnormalities.
    2) NERVE CONDUCTION STUDIES
    a) Nerve conduction studies may be useful in evaluating patients with sensory or motor neuropathies.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.2) DISPOSITION/PARENTERAL EXPOSURE
    6.3.2.1) ADMISSION CRITERIA/PARENTERAL
    A) Patients should be closely monitored until bone marrow suppression resolves. Specialized units or isolation rooms should be considered in patients with severe neutropenia as a protective measure.
    6.3.2.2) HOME CRITERIA/PARENTERAL
    A) There is no data to support home management. Patients with docetaxel overdose need to be admitted.
    6.3.2.3) CONSULT CRITERIA/PARENTERAL
    A) Consult a poison center, a medical toxicologist, and/or an oncologist or nephrologist for assistance in managing patients with docetaxel overdose.
    6.3.2.5) OBSERVATION CRITERIA/PARENTERAL
    A) Patients should be closely monitored in an inpatient setting, with frequent monitoring of vital signs (every 4 hours for the first 24 hours), daily monitoring of CBC with differential until bone marrow suppression is resolved, and monitoring of serum electrolytes, renal function, and hepatic enzymes.

Monitoring

    A) Obtain CBC with differential daily to evaluate for bone marrow suppression (primarily neutropenia). The median time to nadir was 7 days, while the median duration of severe neutropenia (less than 500 cells/mm(3)) was 7 days in therapeutic use. Serial counts should be monitored until patient recovery.
    B) Monitor for clinical evidence of infection, with particular attention to: odontogenic infection, oropharynx, esophagus, soft tissues particularly in the perirectal region, exit and tunnel sites of central venous access devices, upper and lower respiratory tracts, and urinary tract.
    C) Closely monitor liver enzymes, renal function, fluid status and electrolytes. Ensure adequate hydration and correct electrolyte abnormalities as needed.
    D) Monitor vital signs, including temperature.
    E) Obtain an ECG. Continuous cardiac monitoring is indicated in patients with evidence of conduction abnormalities.
    F) Clinically evaluate patients for the development of mucositis and/or peripheral neuropathy.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Docetaxel is only available parenterally; oral exposure is unlikely and activated charcoal and gastric lavage are generally not indicated.
    6.5.3) TREATMENT
    A) SUPPORT
    1) Docetaxel is only available parenterally; oral exposure is unlikely. See the PARENTERAL EXPOSURE section for further information.

Enhanced Elimination

    A) LACK OF EFFICACY
    1) Docetaxel is highly protein bound and has a large volume of distribution; hemodialysis is unlikely to be beneficial.

Range Of Toxicity

Summary

    A) TOXICITY: Limited data. In 2 cases, severe neutropenia, mild asthenia, cutaneous reactions, and mild paresthesia occurred in both patients following a 150 mg/m(2) and a 200 mg/m(2) infusion. Both recovered with supportive care.
    B) THERAPEUTIC DOSE: ADULT: The recommended dose is 60 mg/m(2) to 100 mg/m(2) IV over 1 hour every 3 weeks for various disease states. PEDIATRIC: The safety and efficacy of docetaxel have not been established in pediatric patients.

Therapeutic Dose

    7.2.1) ADULT
    A) DISEASE STATE
    1) BREAST CANCER, METASTATIC
    a) The recommended dose is 60 to 100 mg/m(2) IV over 1 hour every 3 weeks (Prod Info TAXOTERE intravenous injection concentrate, 2014).
    2) BREAST CANCER, OPERABLE
    a) The recommended dose for operable, node-positive breast cancer is 75 mg/m(2) IV over 1 hour, after doxorubicin and cyclophosphamide, every 3 weeks for 6 courses (Prod Info TAXOTERE intravenous injection concentrate, 2014).
    3) GASTRIC CANCER
    a) The recommended dose is 75 mg/m(2) IV over 1 hour every 3 weeks, combined with cisplatin and fluorouracil for untreated advanced gastric cancer (Prod Info TAXOTERE intravenous injection concentrate, 2014).
    4) HEAD AND NECK CANCER
    a) The recommended dose is 75 mg/m(2) IV over 1 hour every 3 weeks, followed by cisplatin and fluorouracil (Prod Info TAXOTERE intravenous injection concentrate, 2014).
    5) NON-SMALL CELL LUNG CANCER
    a) The recommended dose is 75 mg/m(2) IV over 1 hour every 3 weeks either as monotherapy in patients treated previously with plantimum-based chemotherapy, or followed by cisplatin in previously untreated patients (Prod Info TAXOTERE intravenous injection concentrate, 2014).
    6) PROSTATE CANCER, METASTATIC
    a) The recommended dose is 75 mg/m(2) IV over 1 hour every 3 weeks (Prod Info TAXOTERE intravenous injection concentrate, 2014).
    7.2.2) PEDIATRIC
    A) Safety and efficacy in the pediatric or adolescent population have not been established (Prod Info TAXOTERE intravenous injection concentrate, 2014).
    B) During a dose-finding phase I clinical trial, docetaxel monotherapy was evaluated for the treatment of a variety of refractory solid tumors in 61 pediatric patients with a median age of 12.5 years (range, 1 to 22 years). The recommended dose was 125 mg/m(2) as a 1-hour IV infusion administered every 21 days, with the primary dose-limiting toxicity of neutropenia (Prod Info TAXOTERE intravenous injection concentrate, 2014).
    C) A dose of 100 mg/m(2) has been used in children with relapsed/refractory sarcomas (Mora et al, 2009).

Maximum Tolerated Exposure

    A) In 2 cases, severe neutropenia, mild asthenia, cutaneous reactions, and mild paresthesia occurred in both patients following a 150 mg/m(2) and a 200 mg/m(2) infusion. Both recovered with supportive care (Prod Info TAXOTERE(R) IV injection, 2010).

Pharmacology Toxicology

Pharmacologic Mechanism

    A) ANTINEOPLASTIC ACTION: Docetaxel inhibits cell division by promoting microtubule stabilization and assembly (Prod Info TAXOTERE intravenous injection concentrate, 2015).
    1) Unlike other antimicrotubule agents that induce microtubule disassembly (eg, vinca alkaloids and colchicine), paclitaxel and docetaxel promote the assembly of microtubules from tubulin dimers, and stabilize microtubules by preventing depolymerization (Prod Info TAXOTERE intravenous injection concentrate, 2015; Manfredi et al, 1982; Manfredi & Horwitz, 1984; Schiff et al, 1979; Hamel et al, 1981; Rowinsky et al, 1990; Rowinsky et al, 1989; Lipton et al, 1989; (CDER, 1997)).

Physicochemical

Physical Characteristics

    A) Docetaxel is a white to almost white powder that is highly lipophilic and practically insoluble in water (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010).

Molecular Weight

    A) 861.9 (Prod Info TAXOTERE(R) injection concentrate IV infusion, 2010)

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