docetaxel

High Alert

Locally advanced or metastatic breast cancer after failure of prior chemotherapy.
Adjuvant treatment of operable node-positive breast cancer (in combination with doxorubicin and cyclophosphamide).
Locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of prior platinum-based regimen.
Unresectable, locally advanced, or metastatic NSCLC in patients who have not previously received chemotherapy for this condition (in combination with cisplatin).
Metastatic castration-resistant prostate cancer (in combination with prednisone).
Locally advanced squamous cell carcinoma of the head and neck (in combination with cisplatin and fluorouracil).
Advanced gastric adenocarcinoma (including adenocarcinoma of the gastroesophageal junction) in patients who have not received prior chemotherapy for advanced disease (in combination 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: Widely distributed to tissues.

Metabolism/Excretion: Extensively metabolized by the liver via the CYP3A isoenzyme; metabolites undergo fecal elimination.

Half-Life: 116 hr.

Time/Action Profile ⬆ ⬇

(effect on blood counts)

ROUTE	ONSET	PEAK	DURATION
IV	rapid	5–9 days	7 days

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to docetaxel, paclitaxel, or medications formulated with polysorbate 80;
Known alcohol intolerance;
Neutrophil count <1500/mm³;
Liver impairment (serum bilirubin > upper limit of normal [ULN], ALT and/or AST >1.5 times ULN, with alkaline phosphatase >2.5 times ULN);
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: peripheral edema, CARDIAC TAMPONADE, PERICARDIAL EFFUSION

Derm: alopecia, edema, rash, ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS (AGEP), dermatitis, desquamation, erythema, nail disorders, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN)

EENT: cystoid macular edema

GI: diarrhea, nausea, stomatitis, vomiting, ASCITES, ENTEROCOLITIS, NEUTROPENIC COLITIS

GU: ↓fertility (males), amenorrhea

Hemat: anemia, leukopenia, thrombocytopenia

Local: injection site reactions

MS: myalgia, arthralgia

Neuro: fatigue, weakness, alcohol intoxication, neurosensory deficits, peripheral neuropathy

Resp: ACUTE RESPIRATORY DISTRESS SYNDROME, bronchospasm, dyspnea, INTERSTITIAL LUNG DISEASE, PULMONARY EDEMA, PULMONARY FIBROSIS

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), MALIGNANCY (INCLUDING LEUKEMIAS, MYELODYSPLASTIC SYNDROME, NON-HODGKIN'S LYMPHOMA, AND RENAL CANCER), tumor lysis syndrome

Interactions ⬆ ⬇

Drug-drug:

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

Route/Dosage ⬆ ⬇

IV (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)

Solution for injection (concentrate): 10 mg/mL (dose of 100 mg/m² contains 0.15 g/m² of ethanol); 20 mg/mL (dose of 100 mg/m² contains 1.975 g/m² of ethanol)

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 signs and symptoms of hypersensitivity reactions (bronchospasm, hypotension, erythema) continuously during infusion; most common after first and second doses of docetaxel. Treat mild to moderate reactions symptomatically and slow or stop infusion until reaction subsides. Discontinue therapy if severe reactions occur. 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 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), premedicate with dexamethasone.
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. May cause SJS, TEN, and AGEP; permanently discontinue docetaxel if severe cutaneous reactions occur.
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 especially in patients receiving docetaxel with cisplatin and fluorouracil If Grade 3 diarrhea occurs, 1st episode: ↓ fluorouracil dose by 20%. 2nd episode: ↓ docetaxel dose by 20%. If Grade 4 diarrhea occurs, 1st episode: ↓ docetaxel and fluorouracil doses by 20%. 2nd episode: discontinue treatment. If Grade 3 stomatitis/mucositis occurs, 1st episode: ↓ fluorouracil dose by 20%. 2nd episode: stop fluorouracil only, at all subsequent cycles. 3rd episode: ↓ docetaxel dose by 20%. If Grade 4 stomatitis/mucositis occurs, 1st episode: stop fluorouracil only, at all subsequent cycles. 2nd episode: docetaxel dose by 20%
Monitor for tumor lysis syndrome due to rapid reduction in tumor volume (acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hypophosphatemia). Risks are higher in patients with greater tumor burden and rapidly proliferating tumors; may be fatal. Correct electrolyte abnormalities, monitor renal function and fluid balance, and administer supportive care, including dialysis, as indicated.
Monitor for signs and symptoms of fluid retention (edema, weight gain), usually begins with peripheral edema in lower extremities. May be treated with sodium restriction and diuretics.
Monitor patients for second primary malignancies.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.Monitor CBC and differential before each treatment. Frequently causes neutropenia (<2000 neutrophils/mm³); may require dose adjustment. If neutrophil count <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 times ULN and alkaline phosphatase ≤2.5 times ULN, or AST/ALT >1.5 to ≤5 times ULN, and alkaline phosphatase >2.5 to ≤5 times ULN,↓ dose by 20%. If AST/ALT >5 times ULN and/or alkaline phosphatase >5 times ULN, discontinue therapy.

Implementation ⬆ ⬇

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 docetaxel with 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.

IV Administration:

Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. If powder or solution comes in contact with skin or mucosa, wash thoroughly with soap and water. Discard equipment in specially designated containers.
Intermittent Infusion: One-vial formulation: Do not dilute one-vial formulation. Solution is ready to add to infusion solution.For injection concentrate: Before dilution, allow vials to stand at room temperature for 5 min. Solution is pale yellow to brownish yellow. Use a 21-gauge needle to withdraw docetaxel from vial; larger bore needles may result in stopper coring and rubber particles. Diluent: Withdraw required amount and inject into 250-mL bag of 0.9% NaCl or D5W. If a dose >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 6 hr.Concentration: 0.3 mg/mL to 0.74 mg/mL. Solution is supersaturated and may crystallize over time. If crystals appear, solution must be discarded.
Rate: Administer over 1 hr.

Patient/Family Teaching ⬆ ⬇

Explain purpose of docetaxel to patient.
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 to avoid alcohol and 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), colitis (abdominal pain or tenderness, diarrhea, with or without fever), yellow skin, weakness, paresthesia, gait disturbances, swelling of the feet, or joint or muscle aches occur.
Alcohol content of docetaxel may impair CNS. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
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.
Advise patient to notify health care professional if changes in vision occur. Obtain a prompt and comprehensive ophthalmologic examination. May require discontinuation of docetaxel and use of a nontaxane cancer therapy.
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.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for 2 mo after last dose of therapy and to avoid breastfeeding during and for 1 wk after last dose. Advise men with female partners of reproductive potential to use effective contraception during and for 4 mo after last dose of therapy. May impair fertility in male patients.
Emphasize the need for periodic lab tests to monitor for side effects.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇