Taxotere

docetaxel

Taxotere

Pharmacologic class: Mitosis inhibitor

Therapeutic class: Antineoplastic

Pregnancy risk category D

FDA Box Warning

• Give under supervision of physician experienced in cancer chemotherapy, in facility with adequate diagnostic and treatment resources.

• Treatment-related death is more likely if patient has abnormal hepatic function, is receiving higher doses, or has non-small-cell lung cancer and history of platinum-based chemotherapy and is receiving drug as a single agent at dosage of 100 mg/m2.

• Generally, drug shouldn't be given to patients with bilirubin level above upper limit of normal (ULN) or those with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) above 1.5 × ULN concomitant with alkaline phosphatase (ALP) level above 2.5 × ULN. Bilirubin elevations or transaminase abnormalities concurrent with ALP abnormalities increases patient's risk for grade 4 neutropenia, febrile neutropenia, infections, severe thrombocytopenia, severe stomatitis, severe skin toxicity, and toxic death. Patients with isolated transaminase elevations above 1.5 × ULN have higher rate of grade 4 febrile neutropenia, but without increased incidence of toxic death. Before each cycle, obtain bilirubin, ALT or AST, and ALP values and have physician review them.

• Don't give to patients with neutrophil count below 1,500 cells/mm3. Obtain frequent blood cell counts to monitor for neutropenia (which may be severe and cause infection).

• Severe hypersensitivity reactions and fatal anaphylaxis (rare) have occurred in patients who received recommended 3-day dexamethasone premedication. If hypersensitivity reaction occurs, discontinue docetaxel immediately and give appropriate therapy. Don't give drug to patients with history of severe hypersensitivity reactions to it or other drugs containing polysorbate 80. Severe fluid retention may occur despite dexamethasone premedication regimen.

Action

Inhibits cellular mitosis by disrupting microtubular network

Availability

Injection concentrate: 20 mg, 80 mg

Indications and dosages

Locally advanced or metastatic breast cancer unresponsive to previous regimens

Adults: 60 to 100 mg/m2 I.V. over 1 hour q 3 weeks as single agent

Adjuvant treatment of operable node-positive breast cancer

Adults: 75 mg/m2 1 hour after doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 q 3 weeks for six courses

Locally advanced or metastatic non-small-cell lung cancer (NSCLC) after platinum therapy failure

Adults: 75 mg/m2 I.V. over 1 hour q 3 weeks as single agent

Unresectable locally advanced or metastatic NSCLC in chemotherapynaïve patients

Adults: 75 mg/m2 I.V. over 1 hour q 3 weeks followed by cisplatin as ordered

Androgen-independent (hormone refractory) metastatic prostate cancer

Adults: 75 mg/m2 I.V. over 1 hour q 3 weeks with 5 mg prednisone P.O. b.i.d. continuously

Gastric adenocarcinoma cancer

Adults: 75 mg/m2 as a 1-hour infusion, followed by cisplatin as a 1- to 3-hour infusion (both on day 1 only), followed by fluorouracil given as a 24-hour continuous I.V. infusion for 5 days, starting at the end of the cisplatin infusion. Treatment is repeated q 3 weeks.

Squamous cell carcinoma of head and neck

Adults:Induction chemotherapy followed by radiotherapy-75 mg/m2 I.V. as 1-hour infusion followed by cisplatin 75 mg/m2 I.V. over 1 hour (both on day 1 only), followed by fluorouracil 750 mg/m2 given as 24-hour continuous I.V. infusion daily for 5 days, starting at end of cisplatin infusion. Treatment is repeated q 3 weeks for four cycles.

Adults:Induction chemotherapy followed by chemoradiotherapy-75 mg/m2 I.V. as 1-hour infusion on day 1, followed by cisplatin 100 mg/m2 I.V. as 30-minute to 3-hour infusion, followed by fluorouracil 1,000 mg/m2/day I.V. as continuous infusion from day 1 to day 4. Treatment is repeated q 3 weeks for three cycles.

Dosage adjustment

• Febrile neutropenia

Contraindications

• Hypersensitivity to drug or polysorbate 80
• Hepatic impairment
• Neutrophil count below 1,500 cells/mm3

Precautions

Use cautiously in:
• females of childbearing age
• pregnant or breastfeeding patients.

Administration

• Assess bilirubin, ALT, AST, and ALP levels before starting each cycle of drug therapy.
• Premedicate patient with oral corticosteroids before docetaxel administration to reduce fluid retention and severity of hypersensitivity reactions.
• Premedicate patient with antiemetics and hydrate with I.V. fluids, as prescribed, before cisplatin administration.

Don't let drug concentrate contact plasticized polyvinyl chloride equipment or devices.
• Know that when used for prostate cancer, drug must be given with prednisone, as prescribed.
• Dilute with accompanying diluent solution; rotate vial gently to mix. Once foam has largely dissipated, withdraw prescribed amount of drug and mix in glass or polypropylene bottle or in plastic bag with 250 ml of normal saline solution or dextrose 5% in water.
• Mix solution thoroughly and infuse over 1 hour, using polyethylene-lined infusion set.

Adverse reactions

CNS: fatigue, asthenia, neurosensory deficits, peripheral neuropathy

CV: peripheral edema, cardiac tamponade, pericardial effusion

GI: nausea, vomiting, diarrhea, stomatitis, ascites

Hematologic: anemia, thrombocytopenia, leukopenia

Musculoskeletal: myalgia, joint pain

Respiratory: bronchospasm, pulmonary edema

Skin: alopecia, rash, dermatitis, desquamation, erythema, nail disorders

Other: edema, hypersensitivity reactions including anaphylaxis

Interactions

Drug-drug.Antineoplastics: additive bone marrow depression

Cyclosporine, erythromycin, ketoconazole, troleandomycin: significant change in docetaxel effects

Live-virus vaccines: increased risk of infection

Patient monitoring

Watch for signs and symptoms of anaphylaxis or other hypersensitivity reactions, especially with first two doses.
• Monitor vital signs and fluid intake and output. Watch for signs and symptoms of fluid overload and bronchospasm.
• Monitor CBC, and assess for signs and symptoms of blood dyscrasias.
• Closely monitor neutrophil and platelet counts before and during therapy.
• Observe I.V. site frequently for extravasation.
• Assess neurologic status to detect neurosensory deficits and peripheral neuropathy.

Patient teaching

• Instruct patient to weigh himself daily and to immediately report sudden weight gain or difficulty breathing.

Tell patient to report signs and symptoms of blood dyscrasias. Inform him that he'll undergo frequent blood testing to monitor these effects.

Advise patient to immediately report rash or difficulty breathing.
• Inform patient that nail disorders and hair loss are common with docetaxel use, but that hair and nails will grow back after therapy ends.
• Advise female patient of childbearing age to use effective contraception during therapy and to notify prescriber if she suspects pregnancy.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs mentioned above.

DOCEtaxel

(doe-se-tax-el) ,

Docefrez

(trade name),

Taxotere

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: taxoids
Pregnancy Category: D

Indications

Breast cancer (locally advanced/metastatic breast cancer or with doxorubicin and cyclophosphamide as adjuvant treatment of node-positive disease).Non–small-cell lung cancer (locally advanced/metastatic) after failure on platinum regimen or with platinum as initial therapy).Advanced metastatic hormone-refractory prostate cancer (with prednisone).Squamous cell carcinoma of the head and neck (locally advanced) with cisplatin and fluorouracil.Gastric adenocarcinoma (locally advanced) with cisplatin and fluorouracil.

Action

Interferes with normal cellular microtubule function required for interphase and mitosis.

Therapeutic effects

Death of rapidly replicating cells, particularly malignant ones.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.
Distribution: Unknown.
Metabolism and Excretion: Extensively metabolized by the liver; metabolites undergo fecal elimination.
Half-life: 11.1 hr.

Time/action profile (effect on blood counts)

ROUTEONSETPEAKDURATION
IVrapid 5–9 days7 days

Contraindications/Precautions

Contraindicated in: Hypersensitivity;Hypersensitivity to polysorbate 80;Known alcohol intolerance;Neutrophil count <1500/mm3;Liver impairment (serum bilirubin > upper limit of normal, ALT and/or AST >1.5 times upper limit of normal, with alkaline phosphatase >2.5 times upper limit of normal); Obstetric / Lactation: Pregnancy or lactation.
Use Cautiously in: Obstetric: Patients with child-bearing potential; Pediatric: Efficacy not established.

Adverse Reactions/Side Effects

Central nervous system

  • fatigue (most frequent)
  • weakness (most frequent)

Respiratory

  • acute respiratory distress syndrome (life-threatening)
  • interstitial lung disease (life-threatening)
  • pulmonary fibrosis (life-threatening)
  • bronchospasm
  • dyspnea

Cardiovascular

  • ascites (life-threatening)
  • cardiac tamponade (life-threatening)
  • pericardial effusion (life-threatening)
  • pulmonary edema (life-threatening)
  • peripheral edema (most frequent)

Gastrointestinal

  • diarrhea (most frequent)
  • nausea (most frequent)
  • stomatitis (most frequent)
  • vomiting (most frequent)

Dermatologic

  • alopecia (most frequent)
  • edema (most frequent)
  • rash (most frequent)
  • dermatitis
  • desquamation
  • erythema
  • nail disorders

Hematologic

  • anemia (most frequent)
  • leukopenia (most frequent)
  • thrombocytopenia (most frequent)
  • leukemia

Local

  • injection site reactions

Musculoskeletal

  • myalgia (most frequent)
  • arthralgia

Neurologic

  • neurosensory deficits
  • peripheral neuropathy

Miscellaneous

  • hypersensitivity reactions, including anaphylaxis (life-threatening)

Interactions

Drug-Drug interaction

↑ bone marrow depression may occur with other antineoplastics or radiation therapy.Strong inhibitors of CYP3A4, including atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, or voriconazole ↑ levels and the risk of toxicity; avoid concomitant use (if need to use, ↓ docetaxel dose by 50%).

Route/Dosage

Intravenous (Adults) Breast cancer—60–100 mg/m2 every 3 wk; Breast cancer adjuvant therapy—75 mg/m2 every 3 wk for 6 cycles (with doxorubicin and cyclophosphamide); Non–small-cell lung cancer—75 mg/m2 every 3 wk (alone or with platinum); Prostate cancer—75 mg/m2 every 3 wk (with oral prednisone); Squamous cell head and neck cancer—75 mg/m2 every 3 wk for 3–4 cycles (with cisplatin and fluorouracil); Gastric adenocarcinoma—75 mg/m2 every 3 wk (with cisplatin and fluorouracil).

Availability (generic available)

Injection concentrate: 10 mg/mL, 20 mg/mL, 40 mg/mL
Lyophilized powder for injection: 20 mg/vial, 80 mg/vial

Nursing implications

Nursing assessment

  • Monitor vital signs before and after administration.
  • Assess infusion site for patency. Docetaxel is not a vesicant. If extravasation occurs, discontinue docetaxel immediately and aspirate the IV needle. Apply cold compresses to the site for 24 hr.
  • Monitor for hypersensitivity reactions continuously during infusion. These are most common after the first and second doses of docetaxel. Reactions may consist of bronchospasm, hypotension, and/or erythema. Mild to moderate reactions may be treated symptomatically and infusion slowed or stopped until reaction subsides. Severe reactions require discontinuation of therapy and symptomatic treatment. Do not readminister docetaxel to patients with previous severe reactions. Severe edema may also occur. Weigh patients before each treatment. Fluid accumulation may result in edema, ascites, and pleural or pericardial effusions. Pretreatment with corticosteroids (such as dexamethasone 8 mg PO twice daily for 3 days, starting 1 day before docetaxel) is recommended to minimize edema and hypersensitivity reactions. PO furosemide may be used to treat edema. For hormone-refractory metastatic prostate cancer (given with prednisone), recommended premedication regimen is dexamethasone 8 mg PO, at 12 hr, 3 hr and 1 hr before docetaxel infusion.
  • Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae; guaiac stools, urine, and emesis) and avoid IM injections and taking rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension.
  • Assess for rash. May occur on feet or hands but may also occur on arms, face, or thorax, usually with pruritus. Rash usually occurs within 1 wk after infusion and resolves before next infusion.
  • Assess for development of neurosensory deficit (paresthesia, dysesthesia, pain, burning). May also cause weakness. Pyridoxine may be used to minimize symptoms. Severe symptoms may require dose reduction or discontinuation.
  • Assess for arthralgia and myalgia, which are usually relieved by nonopioid analgesics but may be severe enough to require treatment with opioid analgesics.
  • Assess for diarrhea and stomatitis. If Grade 3 or 4, reduce dose.
  • Lab Test Considerations: Monitor CBC and differential before each treatment. Frequently causes neutropenia (<2000 neutrophils/mm3); may require dose adjustment. If the neutrophil count is less than 1500/mm3, hold dose. Neutropenia is reversible and not cumulative. The nadir is 8 days, with a duration of 7 days. May also cause thrombocytopenia and anemia.
    • Monitor liver function studies (AST, ALT, alkaline phosphatase, bilirubin) before each cycle. If AST/ALT >2.5 to ≤5 x upper limit of normal and AP ≤2.5 x upper limit of normal, or AST/ALT >1.5 to ≤5 x upper limit of normal and AP >2.5 to ≤5 x ULN, reduce dose by 20%. If AST/ALT >5 x upper limit of normal and/or AP >5 x upper limit of normal discontinue therapy.

Potential Nursing Diagnoses

Risk for infection (Adverse Reactions)
Risk for injury (Adverse Reactions)

Implementation

  • high alert: Fatalities have occurred with chemotherapeutic agents. Before administering, clarify all ambiguous orders; double-check single, daily, and course-of-therapy dose limits; have second practitioner independently double-check original order, calculations, and infusion pump settings. Do not confuse Taxotere (docetaxel) with Taxol (paclitaxel).
  • Premedicate with dexamethasone 8 mg twice daily for 3 days starting 1 day before docetaxel infusion to reduce incidence and severity of fluid retention and hypersensitivity reactions. Premedicate patients with hormone-refractory metastatic prostate cancer with PO dexamethasone 8 mg, at 12 hr, 3 hr and 1 hr before docetaxel infusion.
  • Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard IV equipment in specially designated containers.
  • Intravenous Administration
  • Intermittent Infusion: For injection concentrate: Before dilution, allow vials to stand at room temperature for 5 min. Solution is pale yellow to brownish yellow. For powder for injection: Allow number of vials required for dose to stand at room temperature for 5 min. Reconstitute with diluent provided, 1 mL for 20-mg vial or 4 mL for 80-mg vial. Shake vial to dissolve. Solution should be clear; do not administer solutions that are discolored or contain a precipitate. Allow solution to stand for a few minutes for air bubbles to dissipate. May be refrigerated for up to 8 hrs. Concentration: 20 mg/0.8 mL for 20-mg vial; 24 mg/mL for 80-mg vial. Diluent: Withdraw required amount and inject into 250-mL bag of 0.9% NaCl or D5W. If a dose greater than 200 mg is required, use a larger volume diluent so that concentration of 0.74 mg/mL is not exceeded. Rotate gently to mix. Do not administer solutions that are cloudy or contain a precipitate. Diluted solution must be infused within 4 hrs.Concentration: 0.3 mg/mL to 0.74 mg/mL.
  • Rate: Administer over 1 hr.
  • Y-Site Compatibility: acyclovir, alfentanil, allopurinol, amifostine, amikacin, aminocaproic acid, aminophylline, amiodarone, amphotericin B lipid complex, ampicillin, ampicillin/sulbactam, anidulafungin, argatroban, atracurium, azithromycin, aztreonam, bivalirudin, bleomycin, bumetanide, buprenorphine, busulfan, butorphanol, calcium chloride, calcium gluconate, carboplatin, carmustine, caspofungin, cefazolin, cefepime, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftriaxone, cefuroxime, chlorpromazine, ciprofloxacin, cisatracurium, cisplatin, clindamycin, cyclophosphamide, cyclosporine, cytarabine, dacarbazine, dactinomycin, daptomycin, dexamethasone sodium phosphate, dexmedetomidine, dextrazoxane, diazepam, digoxin, diltiazem, diphenhyrdamine, dobutamine, dolasetron, dopamine, doripenem, doxacurium, doxycycline, droperidol, enalaprilat, ephedrine, epinephrine, epirubicin, ertapenem, erythromycin, esmolol, etoposide, etoposide phosphate, famotidine, fenoldopam, fentanyl, fluconazole, fludarabine, fluorouracil, foscarnet, fosphenytoin, furosemide, ganciclovir, gemcitabine, gentamicin, glycopyrrolate, granisetron, haloperidol, heparin, hydralazine, hydrocortisone, hydromorphone, ifosfamide, imipenem/cilastatin, insulin, irinotecan, isoproterenol, ketorolac, leucovorin, levofloxacin, levorphanol, lidocaine, linezolid, lorazepam, magnesium sulfate, mannitol, meperidine, meropenem, mesna, methotrexate, methyldopate, metoclopramide, metoprolol, metronidazole, midazolam, milrinone, mitoxantrone, morphine, moxifloxacin, nafcillin, naloxone, nesiritide, nicardipidine, nitroglycerin, nitroprusside, norepinephrine, octreotide, ondansetron, oxaliplatin, palonosetron, pamidronate, pancuronium, pantoprazole, pemetrexed, pentamidine, pentazocine, pentobarbital, phenobarbital, phentolamine, phenylephrine, piperacillin/tazobactam, potassium acetate, potassium chloride, potassium phosphates, procainamide, prochlorperazine, promethazine, propranolol, quinupristin/dalfopristin, ranitidine, remifentanil, rituximab, rocuronium, sodium acetate, sodium bicarbonate, sodium phosphates, succinylcholine, sufentanil, tacrolimus, teniposide, theophylline, thiotepa, ticarcillin/clavulanate, tigecycline, tirofiban, tobramycin, tolazoline, trastuzumab, trimethoprim/sulfamethoxazole, vancomycin, vecuronium, vinblastine, vincristine, vinorelbine, voriconazole, zidovudine, zoledronic acid
  • Y-Site Incompatibility: amphotericin B colloidal, amphotericin B liposome, dantrolane, doxorubicin liposome, idarubicin, methylprednisolone, nalbuphine, phenytoin

Patient/Family Teaching

  • Instruct patient to report symptoms of hypersensitivity reactions (trouble breathing; sudden swelling of face, lips, tongue, throat; trouble swallowing; hives; rash; redness all over body) to health care professional immediately.
  • Advise patient to notify health care professional if fever >101°F; chills; sore throat; signs of infection; bleeding gums; bruising; petechiae; or blood in urine, stool, or emesis occur. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor.
  • Patient should be cautioned not to drink alcoholic beverages or take products containing aspirin or NSAIDs.
  • Fatigue is a frequent side effect of docetaxel. Advise patient that frequent rest periods and pacing of activities may minimize fatigue.
  • Instruct patient to notify health care professional if signs of fluid retention (peripheral edema in the lower extremities, weight gain, dyspnea), abdominal pain, yellow skin, weakness, paresthesia, gait disturbances, swelling of the feet, or joint or muscle aches occur.
  • Instruct patient to inspect oral mucosa for redness and ulceration. If mouth sores occur, advise patient to use sponge brush and rinse mouth with water after eating and drinking.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
  • Discuss with patient the possibility of hair loss. Complete hair loss usually begins after 1 or 2 treatments and is reversible after discontinuation of therapy. Explore coping strategies.
  • Instruct patient not to receive any vaccinations without advice of health care professional.
  • Advise female patients to use effective contraception during therapy and to notify health care professional if pregnancy is planned or suspected or if breast feeding.
  • Emphasize the need for periodic lab tests to monitor for side effects.

Evaluation/Desired Outcomes

  • Decrease in size or spread of malignancy in women with advanced breast cancer.
  • Decrease in size or spread of malignancy in locally advanced or metastatic non–small-cell lung cancer, squamous cell carcinoma of the head and neck, and gastric adenocarcinoma.
  • Decreased size or spread of advanced metastatic hormone-refractory prostate cancer.

Taxotere

(tăk′sə-tĕr′, -tîr′)
n.
A trademark for the drug docetaxel.

Taxotere®

Docetaxol, see there.
Mentioned in ?
References in periodicals archive ?
Food and Drug Administration (FDA) to discuss a single clinical study to support approval of ANX-514 (docetaxel for injectable emulsion), a detergent-free reformulation of Taxotere (docetaxel).
The FDA has approved Taxotere (docetaxel) Injection Concentrate for use in combination with cisplatin and fluorouracil prior to radiotherapy for the treatment of patients with inoperable, locally advanced squamous cell carcinoma of the head and neck (SCCHN).
Thousands of men in Scotland will miss out on the life-prolonging chemotherapy drug Taxotere, despite trials proving it is the most effective treatment around.
New data suggests that the combination of DN-101 and Taxotere(R) (docetaxel) reduced the occurrence of serious adverse events (SAEs) in patients with advanced prostate cancer, compared to those receiving Taxotere and placebo, announced Novacea, Inc.
Tokyo, Japan, Aug 22, 2005 - (JCNN) - Aventis Pharma of the sanofi-aventis Group announced on August 19 that it has obtained additional approval for TAXOTERE Injection, its proprietary taxoid antitumor agent, from the Ministry of Health, Labor and Welfare as of August 18.
These in vitro data support our plans to initiate additional clinical trials evaluating satraplatin in combination with a variety of other anticancer treatments, including a Phase 1 study with TAXOTERE (docetaxel), which is planned to start in the next few months.
A parallel study comparing Taxotere and estramustine (Emcyt), an antineoplastic compound that contains estradiol and is approved for prostate cancer, to mitoxantrone and prednisone found about a 1.
Researchers will compare a chemotherapy regime including the drug Taxotere - never before available in the UK as a first-time treatment - with regimes already used in British hospitals.
For women whose breast cancer is no longer responding to standard treatment with doxorubicin, a new drug, Taxotere, received FDA approval in June.
Dutch and Canadian researchers also report that Taxotere proved very active against breast cancer.
GlobalData's pharmaceuticals report, Taxotere (Breast Cancer) - Analysis and Forecasts to 2020 provides Taxotere sales estimates for US, EU5 and Japan.