No

Antineoplastic Agent, Natural Source (Plant) Derivative

Treatment of patients with locally advanced or metastatic breast cancer who have progressed during anthracycline-based therapy or have relapsed during anthracycline-based adjuvant therapy; treatment of patients with locally advanced or metastatic nonsmall cell lung cancer after failure of prior platinum-based chemotherapy

D

History of hypersensitivity to any component

Early studies reported severe hypersensitivity reactions characterized by hypotension, bronchospasms, or minor reactions characterized by generalized rash/erythema. The overall incidence was 25% in patients who did not receive premedication.

Premedication to reduce fluid retention and hypersensitivity reactions: Oral dexamethasone 8 mg twice daily for 5 days starting one day prior to docetaxel exposure. There is also data to support that a 3-day corticosteroid regimen (oral dexamethasone 8 mg twice daily for 3 days starting one day prior to docetaxel exposure) was as effective as the standard 5-day regimen in reducing the incidence and severity of fluid retention. In addition, the 3-day regimen had a more favorable safety profile.

Neutropenia was the dose-limiting toxicity; however this rarely resulted in treatment delays and prophylactic colony stimulating factors have not been routinely used. Patients with increased liver function tests experienced more episodes of neutropenia with a greater number of severe infections. Patients with an absolute neutrophil count <1500 cells/mm³ should not receive docetaxel.

Irritant chemotherapy

>10%:

Central nervous system: Fever

Dermatologic: Alopecia

Gastrointestinal: Nausea, vomiting, diarrhea, stomatitis

Hematologic: Neutropenia, leukopenia, thrombocytopenia, anemia

Neuromuscular & skeletal: Myalgia

1% to 10%: Cardiovascular: Severe fluid retention: poorly tolerated peripheral edema, generalized edema, pleural effusion requiring urgent drainage, dyspnea at rest, cardiac tamponade or pronounced abdominal distention (due to ascites)

<1%: Hypersensitivity reactions, myocardial infarction, gastrointestinal perforation, neutropenic enterocolitis

CYP3A3/4 enzyme substrate

Store intact vials at refrigeration (2°C to 8°C/36°F to 47°F) and protect from light. Intact vials of solution should be further diluted with 13% (w/w) ethanol/water to a final concentration of 10 mg/mL.

Non-PVC tubing must be used. Diluted solutions are stable for up to 4 weeks at room temperature (15°C to 25°C/59°F to 77°F) in polyolefin containers. (Thiesen J and Kramer I, Pharm World Sci, 1999, 21(3):137-41.)

Although the stability of some antineoplastic agents may be long, it is probably considered good pharmaceutical practice to allow a maximum expiration dating of 24 hours due to possible sterility concerns.

Semisynthetic agent prepared from a noncytotoxic precursor which is extracted from the needles of the European Yew Taxus baccata. Docetaxel differs structurally from the prototype taxoid, paclitaxel, by substitutions at the C-10 and C-5 positions. It is an antimicrotubule agent, but exhibits a unique mechanism of action. Unlike other antimicrotubule agents that induce microtubule disassembly (eg, vinca alkaloids and colchicine), docetaxel promotes the assembly of microtubules from tubulin dimers, and inhibits the depolymerization of tubulin which leads to bundles of microtubules in the cell.

Administered by I.V. infusion and exhibits linear pharmacokinetics at the recommended dosage range

Protein binding: 94% mainly to alpha₁-acid glycoprotein, albumin, and lipoproteins

Metabolism: Oxidative metabolism by the liver. Isoenzymes of cytochrome P-450 (CYA3A) are involved in the metabolism

Half-lifes; a, b, and g phases are 4 minutes, 36 minutes, and 11.1 hours, respectively

Elimination: Following oxidative metabolism, docetaxel is eliminated in both urine (6%) and feces (75%) with approximately 80% eliminated in the first 48 hours

Mean values for total body clearance 21 L/hour/m²

Corticosteroids (oral dexamethasone 8 mg twice daily for 3 days or 5 days starting 1 day prior to docetaxel administration) are necessary to reduce the potential for hypersensitivity and severe fluid retention

Locally advanced or metastatic carcinoma of the breast: 60-100 mg/m² over 1 hour every 3 weeks

Dosage adjustment in patients who are initially started at 100 mg/m² (>1 week), cumulative cutaneous reactions, or severe peripheral neuropathy: 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

Dosing adjustment in hepatic impairment:

Total bilirubin greater than or equal to the upper limit of normal (ULN), or AST/ALT >1.5 times the ULN concomitant with alkaline phosphatase >2.5 times the ULN: Docetaxel should not be administered secondary to increased incidence of treatment-related mortality

Monitor for hypersensitivity reactions and fluid retention

None reported

May cause leukopenia; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

This medication can only be administered I.V. During therapy, do not use alcohol, aspirin-containing products, and OTC medications without consulting prescriber. It is important to maintain adequate nutrition and hydration (2-3 L/day of fluids unless instructed to restrict fluid intake) during therapy; frequent small meals may help. You may experience nausea or vomiting (frequent small meals, frequent mouth care, sucking lozenges, or chewing gum may help); you may experience loss of hair (reversible); you will be more susceptible to infection (avoid crowds and exposure to infection as much as possible). Urine may turn red-brown (normal). Yogurt or buttermilk may help reduce diarrhea (if unresolved, contact prescriber for medication relief). Report swelling of extremities, difficulty breathing, unusual weight gain, abdominal distention, fever, chills, unusual bruising or bleeding, signs of infection, excessive fatigue, or unresolved diarrhea. Breast-feeding precautions: Do not breast-feed.

Injection: 20 mg/mL (0.5 mL), 40 mg/mL (0.5 mL, 2 mL), 80 mg/mL (2 mL)

Bruno R and Sanderink GJ, "Pharmacokinetics and Metabolism of Taxotere® (Docetaxel)," Cancer Surv, 1993, 17:305-13.

Cortes JE and Pazdur R, "Docetaxel," J Clin Oncol, 1995, 13(10):2643-55.

Fulton B and Spencer CM, "Docetaxel. A Review of Its Pharmacodynamic and Pharmacokinetic Properties and Therapeutic Efficacy in the Management of Metastatic Breast Cancer," Drugs, 1996, 51(6):1075-92.

Ravdin PM, "The International Experience With Docetaxel in the Treatment of Breast Cancer," Oncology, 1997, 11(3 Suppl 2):38-42.

Trudeau ME, "Docetaxel: A Review of Its Pharmacology and Clinical Activity," Can J Oncol, 1996, 6(1):443-57.