Dosing and uses of Taxotere, Docefrez (docetaxel)
Adult dosage forms and strengths
injectable solution
- 10mg/mL (2mL, 8mL, 16mL vials)
- 20mg/mL (1mL, 4mL vials)
alcohol-free solution for injection
- 20mg/mL
- 80mg/4mL
- 160mg/8mL
Breast Cancer
Locally advanced or metastatic
- For locally advanced or metastatic breast cancer after failure of prior chemotherapy
- Monotherapy: 60-100 mg/m² IV over 1 hr q3Weeks
Operable node-positive
- Adjuvant combination therapy: 75 mg/m² IV 1 hr after doxorubicin and cyclophosphamide q3Weeks x 6 cycles
Dosage modifications (advanced or metastatic)
- Inital 100 mg/m²
- Febrile neutropenia, ANC <500/mm³ for >1 week, or severe/cumulative cutaneous reactions
- Reduce first to 75 mg/m²
- If AEs persist: Reduce further to 55 mg/m² or discontinue
Dosage modifications (adjuvant treatment)
- Initial: 75 mg/m²
- Reduce to 60 mg/m² in patients with febrile neutropenia treated with G-CSF, or severe or cumulative cutaneous or neurosensory reactions
Other dosage modifications
- Grade 3 peripheral neuropathy: Discontinue
- Combo therapy (with doxorubicin and cyclophosphamide): Febrile neutropenia (give G-CSF in all, if continues, reduce to 60 mg/m², continue G-CSF)
- Grade 3/4 Stomatitis: Decrease to 60 mg/m²
- Severe/cumulative cutaneous reactions, moderate neurosensory S/S: Reduce to 60 mg/m²
- Discontinue if adverse effects persists
Non-small Cell Lung Cancer
Indicated for treatment (as monotherapy) in patients with locally advanced or metastatic NSCLC after failure of prior platinum-based chemotherapy
Also indicated in combination with cisplatin for the treatment of unresectable, locally advanced or metastatic NSCLC in patients who have not previously received chemotherapy
75 mg/m² IV over 1 hour q3Weeks
Dose Modifications (Monotherapy)
- Febrile neutropenia, ANC <500/mm³ for >1 week, other grade 3/4 nonhematological toxicities, severe/cumulative cutaneous reactions (withhold treatment until resolution; THEN, resume at 55 mg/m²)
- Grade 3 peripheral neuropathy: Discontinue
Dose Modifications (Combination Therapy)
- Febrile neutropenia, serious non-hematologic toxicities: Reduce first to 65 mg/m²; may reduce further to 50 mg/m²
Gastric Cancer
Indicated 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
Day 1: 75 mg/m² IV infusion over 1 hour, followed by cisplatin 75 mg/m² as a 1-3 hr infusion
Post cisplatin: Fluorouracil 750 mg/m² qDay given as a 24-hr continuous infusion for 5 days
Repeat cycle q3Weeks
Dose modifications (Neutropenia)
- Febrile neutropenia, prolonged neutropenia or neutropenic infection
- First time: Use G-CSF
- If continues despite G-CSF: Reduce to 60 mg/m²
- If recurs thereafter: Reduce to 45 mg/m²
Grade 4 thrombocytopenia
- Do not resume until ANC >1500/mm³ and platelets >100,000/mm³
- Reduce to 60 mg/m²
- If toxicities persist: Discontinue
Diarrhea
- Grade 3 (first episode): Reduce fluorouracil dose by 20%
- Grade 3 (second episode): Then reduce docetaxel dose by 20%
- Grade 4 (first episode): Reduce docetaxel & fluorouracil doses by 20%
- Grade 4 (second episode): Discontinue treatment
Hepatotoxicity
- AST/ALT 2.5-5 times ULN & alkaline phosphatase 2.5 times ULN, OR AST/ALT 1.5-5 times ULN & alkaline phosphatase 2.5-5 times ULN: Reduce by 20%
- If AST/ALT >5 times upper limit of normal &/or alkaline phosphatase >5 times ULN: Discontinue
Head & Neck Cancer
Indicated in combination with cisplatin and fluorouracil for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN)
Induction chemotherapy followed by radiotherapy
- For the induction treatment of locally advanced inoperable SCCHN
- Day 1: 75 mg/m² IV infusion over 1 hour, followed by cisplatin 75 mg/m² as a 1 hr infusion
- Post cisplatin: Fluorouracil 750 mg/m² qDay given as a 24-hr continuous IV infusion times 5 days
- Repeat cycle q3Weeks 4 times
Induction chemotherapy followed by chemoradiotherapy
- For the induction treatment of patients with locally advanced (unresectable, low surgical cure, or organ preservation) SCCHN
- Day 1: 75 mg/m² IV infusion over 1 hr, followed by cisplatin 100 mg/m² as a 0.5-3 hr IV infusion
- Post cisplatin: Fluorouracil 1000 mg/m² qDay given as a 24-hr continuous IV infusion from day 1 to day 4
- Repeat cycle q3Weeks times 3 cycles
Dose Modifications
- As with gastric cancer
Prostate Cancer
Indicated for hormone-refractory metastatic prostate cancer in combination with prednisone
75 mg/m² IV over 1 hr q3Weeks with daily prednisone 5 mg PO q12hr
Dose modifications
- Febrile neutropenia, ANC <500/mm³ for >1 week, or severe/cumulative cutaneous reactions, moderate neurosensory S/S
- Reduce to 60 mg/m²
- If AEs persist: Discontinue
Renal Impairment
Dose adjustment not necessary
Hepatic Impairment
Do not administer if AST/ALT >5 times ULN or lakaline phosphatase >5 times ULn
Reduce dose by 20% if AST/ALT >2.5 - 5 times ULN and alkaline is 2.5 times ULN or lower; alternatively lower the dose by 20% if AST/ALT > 1.5-5 times ULN and alkaline phosphatase >2.5-5 times ULn
Alcohol content of docetaxel injection concentrate should be taken into account when given to patients with hepatic impairment
Administration
Premedicate to prevent hypersensitivity reactions (eg, dexamethasone)
Monitor: CBC, LFTs
Other Indications & Uses
Off-label: Melanoma, NHL, urothelial cancer, ovarian cancer, soft-tissue sarcoma
Pediatric dosage forms and strengths
Safety and efficacy not established
Investigational use for a variety of solid tumors in children is ongoing
Docetaxel has been studied in a total of 289 pediatric patients: 239 in 2 trials with monotherapy and 50 in combination treatment with cisplatin and 5-fluorouracil (see Prescribing Information)
Taxotere, Docefrez (docetaxel) adverse (side) effects
Varies according to indication and treatment regimen
>50%
Alopecia
Anemia
Leukopenia
Neutropenia
Asthenia
10-50%
Fever
Infections
Fluid retention
Hypersensitivity
Skin reactions
Diarrhea
Nausea
Vomiting
Sensory neuropathy
Myalgia
Nail changes
1-10%
Arthralgia
Thrombocytopenia
Postmarketing Reports
Diffuse pain, chest pain, radiation recall phenomenon
Atrial fibrillation, DVT, ECG abnormalities, thrombophlebitis, pulmonary embolism, syncope, tachycardia, myocardial infarction
Bullous eruptions (eg, erythema multiforme, Stevens-Johnson syndrome, TEN, scleroderma-like changes usually preceded by peripheral lymphedema), cutaneous lupus erythematosus, severe hand and foot syndrome may occur
Bleeding episodes, DIC often in association with sepsis or multiorgan failure, acute myeloid leukemia and myelodysplastic syndrome
Anaphylactic shock, very rarely these cases resulted in a fatal outcome in patients who received premedication
Hepatitis, sometimes fatal primarily in patients with pre-existing liver disorders
Confusion, rare cases of seizures or transient loss of consciousness
Conjunctivitis, lacrimation or lacrimation with or without conjunctivitis; excessive tearing (possible lacrimal duct obstruction); transient visual disturbances (flashes, flashing lights, scotomata) typically occurring during drug infusion and in association with hypersensitivity reactions; cystoid macular edema reported when treated with docetaxel injection concentrate
Rare cases of ototoxicity, hearing disorders and/or hearing loss, including cases associated with other ototoxic drugs
Dyspnea, acute pulmonary edema, acute respiratory distress syndrome/pneumonitis, interstitial lung disease, interstitial pneumonia, respiratory failure, pulmonary fibrosis, radiation pneumonitis (with concomitant radiotherapy)
Hyponatremia
Permanent or irreversible alopecia
Warnings
Black box warnings
The drug should be administered under the supervision of an experienced cancer chemotherapy physician
Increased mortality reported in patients with liver impairment receiving higher doses, patients with non-small lung cancer, and a history of platinum-based chemotherapy receiving docetaxel as a single agent at a dose of 100 mg/m²
Patients with elevations in bilirubin or abnormalities of transaminase concurrent with alkaline phosphatase are at increased risk of developing grade 4 neutropenia, febrile neutropenia, infections, severe neutropenia, severe stomatitis, and toxic death
Generally not given if bilirubin >ULN, or if SGOT and/or SGPT >1.5 x ULN concomitant with alkaline phosphatase >2.5 x ULn
Perform blood cell counts on all patients receiving docetaxel; if neutrophil count <1500 cells/mm3, do not administer
Severe hypersensitivity reactions, characterized by generalized rash/erythema, hypotension, and/or bronchospasm, or very rarely fatal anaphylaxis, reported in patients receiving the recommended 3-day dexamethasone premedication; discontinue infusion and administer appropriate therapy if hypersensitivity reaction occurs
Do not give docetaxel to patients with documented hypersensitivity to the drug or drugs formulated with polysorbate 80
Severe fluid retention may occur despite use of a 3-day dexamethasone premedication regimen; it may be characterized by poorly tolerated peripheral edema, generalized edema, pleural effusion requiring urgent drainage, dyspnea at rest, cardiac tamponade, or pronounced abdominal distention (due to ascites)
Contraindications
Hypersensitivity to docetaxel or polysorbate 80
Solid tumor with baseline ANC<1500/cu.mm
Cautions
Irritant; use caution
Treatment-related mortality higher in patients with hepatic impairment, those receiving higher doses, and in patients with NSCLC and history of prior platinum-based chemotherapy who receive docetaxel as a monotherapy at 100 mg/m²
Monitor for delayed myelodysplasia or myeloid leukemia in patients who received docetaxel injection concentrate, doxorubicin and cyclophosphamide
Coadministration with CYP3A4 inhibitors may increase exposure to docetaxel and should be avoided; consider docetaxel dose reduction if unable to avoid
Consider adjusting dose if cutaneous reactions like erythema of the extremities with edema followed by desquamation occur
Risk of severe fluid retention even with dexamethasone
Women of childbearing potential should not become pregnant when receiving docetaxel injection concentrate; it causes fetal harm
Reactions including paresthesia, dysesthesia, and pain may occur; severe neurosensory symptoms require dose adjustment or discontinuation if persistent
Consider therapy discontinuation if severe asthenia occurs
Cystoid macular edema reported and requires treatment discontinuation
The diluent for docetaxel contains 13% ethanol; alcohol intoxication has been reported following IV infusion
Renal failure have been reported, the majority of these cases were associated with concomitant nephrotoxic drugs
Avoid pregnancy
Coadministration with doxorubicin and cyclophosphamide may increase incidence of heart failure compared to nondocetaxel regimens.
Pregnancy and lactation
Pregnancy category: d
Lactation: Not known if excreted in breast milk, do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Taxotere, Docefrez (docetaxel)
Mechanism of action
Semisynthetic taxane, prevents depolymerization of cellular microtubules, which results in DNA, RNA, and protein synthesis inhibition
Pharmacokinetics
Half-life elimination: 11 hr (terminal)
Protein bound: 94-97%
Vd: 80-90 L/m²
Metabolism: Liver (CYP3A4)
Clearance: 21 L/hr/m²
rExcretion: Feces 75%; urine 6%
Administration
IV Incompatibilities
Y-site: amphotericin B, doxorubicin liposomal, methylprednisolone sodium succinate, nalbuphine
IV Compatibilities
Solution: D5W, Ns
Y-site (partial list): acyclovir, ampicillin, ampicillin/sulbactam, most cephalosporins, clindamycin, diphenhydramine, dopamine, fluconazole, gemcitabine, heparin, hydromorphone, hydroxyzine, imipenem-cilastatin, lorazepam, meperidine, morphine SO4, ondansetron, KCl, prochlorperazine, NaHCO3, TMP-SMX, vancomycin, zidovudine
IV Preparation
Dual vial formulation
- Requires 2-step dilution
- Reconstitute vial contents (20 mg/0.5 mL or 80 mg/2 mL) with supplied diluent (13% (w/w) ethanol/water) to obtain a 10 mg/mL solution
- Further dilute with NS or D5W to a final concentration of 0.3-0.74 mg/mL and prepare in a glass bottle, polypropylene, or polyolefin plastic bag to prevent leaching of plasticizers
- Use within 4 hr (including the 1 hr infusion)
- Non-PVC tubing must be used
Single vial formulation
- Requires 1-step dilution
- Available as 20 mg/mL solution; further dilute with NS or D5W to a final concentration of 0.3-0.74 mg/mL and prepare in a glass bottle, polypropylene, or polyolefin plastic bag to prevent leaching of plasticizers
- Use within 4 hr (including the 1 hr infusion)
- Non-PVC tubing must be used
IV Administration
Anaphylactoid-like reactions have been reported: premedicate with dexamethasone (Breast CA, NSCLC: 8 mg PO q12hr for 3 days starting 1 day prior to administration of docetaxel; Prostate CA: 8 mg PO at 12 hr-, 3 hr- and 1 hr preinfusion)
Infuse over 1 hr
When administered as sequential infusions, taxane derivatives should be administered before platinum derivatives (cisplatin, carboplatin) to limit myelosuppression and to enhance efficacy
Storage
Store intact vials at 2-25 degrees C (36-77 degrees F)
Protect from light
