Docetaxel Prescribing Information
Docetaxel administered at 100 mg/m2was associated with deaths considered possibly or probably related to treatment in 2.0% (19/965) of metastatic breast cancer patients, both previously treated and untreated, with normal baseline liver function and in 11.5% (7/61) of patients with various tumor types who had abnormal baseline liver function (AST and/or ALT >1.5 times ULN together with AP >2.5 times ULN). Among patients dosed at 60 mg/m2, mortality related to treatment occurred in 0.6% (3/481) of patients with normal liver function, and in 3 of 7 patients with abnormal liver function. Approximately half of these deaths occurred during the first cycle. Sepsis accounted for the majority of the deaths.
Docetaxel administered at a dose of 100 mg/m2in patients with locally advanced or metastatic non-small cell lung cancer who had a history of prior platinum-based chemotherapy was associated with increased treatment-related mortality (14% and 5% in two randomized, controlled studies). There were 2.8% treatment-related deaths among the 176 patients treated at the 75 mg/m2dose in the randomized trials. Among patients who experienced treatment-related mortality at the 75 mg/m2dose level, 3 of 5 patients had an ECOG PS of 2 at study entry [
Patients with elevations of bilirubin or abnormalities of transaminase concurrent with alkaline phosphatase are at increased risk for the development of severe neutropenia, febrile neutropenia, infections, severe thrombocytopenia, severe stomatitis, severe skin toxicity, and toxic death.
Avoid Docetaxel Injection in patients with bilirubin > upper limit of normal (ULN), or to patients with AST and/or ALT >1.5 × ULN concomitant with alkaline phosphatase >2.5 × ULN [
For patients with isolated elevations of transaminase >1.5 × ULN, consider Docetaxel Injection dose modifications [
Measure bilirubin, AST or ALT, and alkaline phosphatase prior to each cycle of Docetaxel Injection therapy.
Perform frequent peripheral blood cell counts on all patients receiving Docetaxel Injection. Do not retreat patients with subsequent cycles of Docetaxel Injection until neutrophils recover to a level >1500 cells/mm3[
A 25% reduction in the dose of Docetaxel Injection is recommended during subsequent cycles following severe neutropenia (<500 cells/mm3) lasting 7 days or more, febrile neutropenia, or a grade 4 infection in a Docetaxel Injection cycle [
Neutropenia (<2000 neutrophils/mm3) occurs in virtually all patients given 60 mg/m2to 100 mg/m2of docetaxel and grade 4 neutropenia (<500 cells/mm3) occurs in 85% of patients given 100 mg/m2and 75% of patients given 60 mg/m2. Frequent monitoring of blood counts is, therefore, essential so that dose can be adjusted. Docetaxel Injection should not be administered to patients with neutrophils <1500 cells/mm3.
Febrile neutropenia occurred in about 12% of patients given 100 mg/m2but was very uncommon in patients given 60 mg/m2.
Hematologic responses, febrile reactions and infections, and rates of septic death for different regimens are dose related [
Three breast cancer patients with severe liver impairment (bilirubin >1.7 times ULN) developed fatal gastrointestinal bleeding associated with severe drug-induced thrombocytopenia. In gastric cancer patients treated with docetaxel in combination with cisplatin and fluorouracil (TCF), febrile neutropenia and/or neutropenic infection occurred in 12% of patients receiving G-CSF compared to 28% who did not. Patients receiving TCF should be closely monitored during the first and subsequent cycles for febrile neutropenia and neutropenic infection [
Docetaxel Injection is contraindicated in patients with:
• neutrophil counts of <1500 cells/mm3[see Warnings and Precautions (5.3)].• a history of severe hypersensitivity reactions to docetaxel or to other drugs formulated with polysorbate 80. Severe reactions, including anaphylaxis, have occurred [see Warnings and Precautions (5.5)].
• Hypersensitivity to docetaxel or polysorbate 80• Neutrophil counts of <1500 cells/mm3
Monitor patients closely for hypersensitivity reactions, especially during the first and second infusions. Severe hypersensitivity reactions characterized by generalized rash/erythema, hypotension and/or bronchospasm, or fatal anaphylaxis, have been reported in patients premedicated with 3 days of corticosteroids. Severe hypersensitivity reactions require immediate discontinuation of the Docetaxel Injection infusion and aggressive therapy. Do not rechallenge patients with a history of severe hypersensitivity reactions with Docetaxel Injection [
Patients who have previously experienced a hypersensitivity reaction to paclitaxel may develop a hypersensitivity reaction to docetaxel that may include severe or fatal reactions such as anaphylaxis. Monitor patients with a previous history of hypersensitivity to paclitaxel closely during initiation of docetaxel therapy. Hypersensitivity reactions may occur within a few minutes following initiation of a Docetaxel Injection infusion. If minor reactions such as flushing or localized skin reactions occur, interruption of therapy is not required. All patients should be premedicated with an oral corticosteroid prior to the initiation of the infusion of Docetaxel Injection [
Severe fluid retention has been reported following docetaxel therapy. Patients should be premedicated with oral corticosteroids prior to each Docetaxel Injection administration to reduce the incidence and severity of fluid retention [
When fluid retention occurs, peripheral edema usually starts in the lower extremities and may become generalized with a median weight gain of 2 kg.
Among 92 breast cancer patients premedicated with 3-day corticosteroids, moderate fluid retention occurred in 27.2% and severe fluid retention in 6.5%. The median cumulative dose to onset of moderate or severe fluid retention was 819 mg/m2. Nine of 92 patients (9.8%) of patients discontinued treatment due to fluid retention: 4 patients discontinued with severe fluid retention; the remaining 5 had mild or moderate fluid retention. The median cumulative dose to treatment discontinuation due to fluid retention was 1021 mg/m2. Fluid retention was completely, but sometimes slowly, reversible with a median of 16 weeks from the last infusion of docetaxel to resolution (range: 0 to 42+ weeks). Patients developing peripheral edema may be treated with standard measures, e.g., salt restriction, oral diuretic(s).
Docetaxel Injection is a microtubule inhibitor indicated for:
• Breast Cancer (BC):single agent for locally advanced or metastatic BC after chemotherapy failure; and with doxorubicin and cyclophosphamide as adjuvant treatment of operable node-positive BC ()1.1 Breast CancerDocetaxel Injection is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy.
Docetaxel Injection in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with operable node-positive breast cancer.
• Non-small Cell Lung Cancer (NSCLC):single agent for locally advanced or metastatic NSCLC after platinum therapy failure; and with cisplatin for unresectable, locally advanced or metastatic untreated NSCLC ()1.2 Non-small Cell Lung CancerDocetaxel Injection as a single agent is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of prior platinum-based chemotherapy.
Docetaxel Injection in combination with cisplatin is indicated for the treatment of patients with unresectable, locally advanced or metastatic non-small cell lung cancer who have not previously received chemotherapy for this condition.
• Castration-Resistant Prostate Cancer (CRPC):with prednisone in metastatic castration-resistant prostate cancer ()1.3 Prostate CancerDocetaxel Injection in combination with prednisone is indicated for the treatment of patients with metastatic castration-resistant prostate cancer.
• Gastric Adenocarcinoma (GC):with cisplatin and fluorouracil for untreated, advanced GC, including the gastroesophageal junction ()1.4 Gastric AdenocarcinomaDocetaxel Injection in combination with cisplatin and fluorouracil is indicated for the treatment of patients with advanced gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have not received prior chemotherapy for advanced disease.
• Squamous Cell Carcinoma of the Head and Neck (SCCHN):with cisplatin and fluorouracil for induction treatment of locally advanced SCCHN ()1.5 Head and Neck CancerDocetaxel Injection in combination with cisplatin and fluorouracil is indicated for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN).
For all indications, toxicities may warrant dosage adjustments [
Patients who are dosed initially at 100 mg/m2and who experience either febrile neutropenia, neutrophils <500 cells/mm3for more than 1 week, or severe or cumulative cutaneous reactions during Docetaxel Injection therapy should have the dosage adjusted from 100 mg/m2to 75 mg/m2. If the patient continues to experience these reactions, the dosage should either be decreased from 75 mg/m2to 55 mg/m2or the treatment should be discontinued. Conversely, patients who are dosed initially at 60 mg/m2and who do not experience febrile neutropenia, neutrophils <500 cells/mm3for more than 1 week, severe or cumulative cutaneous reactions, or severe peripheral neuropathy during Docetaxel Injection therapy may tolerate higher doses. Patients who develop ≥grade 3 peripheral neuropathy should have Docetaxel Injection treatment discontinued entirely.
Docetaxel Injection in combination with doxorubicin and cyclophosphamide should be administered when the neutrophil count is ≥1500 cells/mm3. Patients who experience febrile neutropenia should receive G-CSF in all subsequent cycles. Patients who continue to experience this reaction should remain on G-CSF and have their Docetaxel Injection dose reduced to 60 mg/m2. Patients who experience grade 3 or 4 stomatitis should have their Docetaxel Injection dose decreased to 60 mg/m2. Patients who experience severe or cumulative cutaneous reactions or moderate neurosensory signs and/or symptoms during Docetaxel Injection therapy should have their dosage of Docetaxel Injection reduced from 75 mg/m2to 60 mg/m2. If the patient continues to experience these reactions at 60 mg/m2, treatment should be discontinued.
Patients who are dosed initially at 75 mg/m2and who experience either febrile neutropenia, neutrophils <500 cells/mm3for more than one week, severe or cumulative cutaneous reactions, or other grade 3/4 non-hematological toxicities during Docetaxel Injection treatment should have treatment withheld until resolution of the toxicity and then resumed at 55 mg/m2. Patients who develop ≥grade 3 peripheral neuropathy should have Docetaxel Injection treatment discontinued entirely.
For patients who are dosed initially at Docetaxel Injection 75 mg/m2in combination with cisplatin, and whose nadir of platelet count during the previous course of therapy is <25,000 cells/mm3, in patients who experience febrile neutropenia, and in patients with serious non-hematologic toxicities, the Docetaxel Injection dosage in subsequent cycles should be reduced to 65 mg/m2. In patients who require a further dose reduction, a dose of 50 mg/m2is recommended. For cisplatin dosage adjustments, see manufacturers' prescribing information.
Docetaxel Injection should be administered when the neutrophil count is ≥1500 cells/mm3. Patients who experience either febrile neutropenia, neutrophils <500 cells/mm3for more than one week, severe or cumulative cutaneous reactions or moderate neurosensory signs and/or symptoms during Docetaxel Injection therapy should have the dosage of Docetaxel Injection reduced from 75 mg/m2to 60 mg/m2. If the patient continues to experience these reactions at 60 mg/m2, the treatment should be discontinued.
Patients treated with Docetaxel Injection in combination with cisplatin and fluorouracil must receive antiemetics and appropriate hydration according to current institutional guidelines. In both studies, G-CSF was recommended during the second and/or subsequent cycles in case of febrile neutropenia, or documented infection with neutropenia, or neutropenia lasting more than 7 days. If an episode of febrile neutropenia, prolonged neutropenia or neutropenic infection occurs despite G-CSF use, the Docetaxel Injection dose should be reduced from 75 mg/m2to 60 mg/m2. If subsequent episodes of complicated neutropenia occur the Docetaxel Injection dose should be reduced from 60 mg/m2to 45 mg/m2. In case of grade 4 thrombocytopenia the Docetaxel Injection dose should be reduced from 75 mg/m2to 60 mg/m2. Do not retreat patients with subsequent cycles of Docetaxel Injection until neutrophils recover to a level >1500 cells/mm3[
Recommended dose modifications for toxicities in patients treated with Docetaxel Injection in combination with cisplatin and fluorouracil are shown in Table 1.
Toxicity | Dosage Adjustment |
Diarrhea grade 3 | First episode: reduce fluorouracil dose by 20%. |
Diarrhea grade 4 | First episode: reduce Docetaxel Injection and fluorouracil doses by 20%. |
Stomatitis/mucositis grade 3 | First episode: reduce fluorouracil dose by 20%. |
Stomatitis/mucositis grade 4 | First episode: stop fluorouracil only, at all subsequent cycles. |
Liver dysfunction: In case of AST/ALT >2.5 to ≤5 × ULN and AP ≤2.5 × ULN, or AST/ALT >1.5 to ≤5 × ULN and AP >2.5 to ≤5 × ULN, Docetaxel Injection should be reduced by 20%.
In case of AST/ALT >5 × ULN and/or AP >5 × ULN Docetaxel Injection should be stopped.
The dose modifications for cisplatin and fluorouracil in the gastric cancer study are provided below.
Peripheral Neuropathy: A neurological examination should be performed before entry into the study, and then at least every 2 cycles and at the end of treatment. In the case of neurological signs or symptoms, more frequent examinations should be performed and the following dose modifications can be made according to NCI-CTCAE grade:
• Grade 2: Reduce cisplatin dose by 20%.• Grade 3: Discontinue treatment.
Ototoxicity: In the case of grade 3 toxicity, discontinue treatment.
Nephrotoxicity: In the event of a rise in serum creatinine ≥grade 2 (>1.5 × normal value) despite adequate rehydration, CrCl should be determined before each subsequent cycle and the following dose reductions should be considered (see Table 2).
For other cisplatin dosage adjustments, also refer to the manufacturers' prescribing information.
| CrCl = Creatinine clearance | |
Creatinine Clearance Result Before Next Cycle | Cisplatin Dose Next Cycle |
CrCl ≥60 mL/min | Full dose of cisplatin was given. CrCl was to be repeated before each treatment cycle. |
CrCl between 40 and 59 mL/min | Dose of cisplatin was reduced by 50% at subsequent cycle. If CrCl was >60 mL/min at end of cycle, full cisplatin dose was reinstituted at the next cycle. |
If no recovery was observed, then cisplatin was omitted from the next treatment cycle. | |
CrCl <40 mL/min | Dose of cisplatin was omitted in that treatment cycle only. |
If CrCl was still <40 mL/min at the end of cycle, cisplatin was discontinued. | |
If CrCl was >40 and <60 mL/min at end of cycle, a 50% cisplatin dose was given at the next cycle. | |
If CrCl was >60 mL/min at end of cycle, full cisplatin dose was given at next cycle. | |
For diarrhea and stomatitis, see Table 1.
In the event of grade 2 or greater plantar-palmar toxicity, fluorouracil should be stopped until recovery. The fluorouracil dosage should be reduced by 20%.
For other greater than grade 3 toxicities, except alopecia and anemia, chemotherapy should be delayed (for a maximum of 2 weeks from the planned date of infusion) until resolution to grade ≤1 and then recommenced, if medically appropriate.
For other fluorouracil dosage adjustments, also refer to the manufacturers' prescribing information.
Avoid using concomitant strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and voriconazole). There are no clinical data with a dose adjustment in patients receiving strong CYP3A4 inhibitors. Based on extrapolation from a pharmacokinetic study with ketoconazole in 7 patients, consider a 50% docetaxel dose reduction if patients require coadministration of a strong CYP3A4 inhibitor [
Administer in a facility equipped to manage possible complications (e.g., anaphylaxis).
Docetaxel Injection, USP is a colorless to pale yellow solution available as:
• 20 mg/2 mL (10 mg/mL) single-dose vial• 80 mg/8 mL (10 mg/mL) multiple-dose vial• 160 mg/16 mL (10 mg/mL) multiple-dose vial
• Lactation: Advise women not to breastfeed. ()8.2 LactationRisk SummaryThere is no information regarding the presence of docetaxel in human milk, or on its effects on milk production or the breastfed child. No lactation studies in animals have been conducted. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with Docetaxel Injection and for 1 week after the last dose.
• Females and Males of Reproductive Potential: Verify pregnancy status of females prior to initiation of Docetaxel Injection. ()8.3 Females and Males of Reproductive PotentialBased on findings in animals, Docetaxel Injection can cause fetal harm when administered to a pregnant woman
[see Use in Specific Populations (8.1)].Pregnancy TestingVerify pregnancy status in females of reproductive potential prior to initiating Docetaxel Injection.
ContraceptionFemalesBased on genetic toxicity findings, advise females of reproductive potential to use effective contraception during treatment and for 2 months after the last dose of Docetaxel Injection.
MalesBased on genetic toxicity findings, advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 4 months after the last dose of Docetaxel Injection.
InfertilityBased on findings in animal studies, Docetaxel Injection may impair fertility in males of reproductive potential [
see Nonclinical Toxicology (13.1)].
Docetaxel Injection is contraindicated in patients with:
• neutrophil counts of <1500 cells/mm3 [see].5.3 Hematologic EffectsPerform frequent peripheral blood cell counts on all patients receiving Docetaxel Injection. Do not retreat patients with subsequent cycles of Docetaxel Injection until neutrophils recover to a level >1500 cells/mm3[
see Contraindications (4)]. Avoid retreating patients until platelets recover to a level >100,000 cells/mm3.A 25% reduction in the dose of Docetaxel Injection is recommended during subsequent cycles following severe neutropenia (<500 cells/mm3) lasting 7 days or more, febrile neutropenia, or a grade 4 infection in a Docetaxel Injection cycle [
see Dosage and Administration (2.7)].Neutropenia (<2000 neutrophils/mm3) occurs in virtually all patients given 60 mg/m2to 100 mg/m2of docetaxel and grade 4 neutropenia (<500 cells/mm3) occurs in 85% of patients given 100 mg/m2and 75% of patients given 60 mg/m2. Frequent monitoring of blood counts is, therefore, essential so that dose can be adjusted. Docetaxel Injection should not be administered to patients with neutrophils <1500 cells/mm3.
Febrile neutropenia occurred in about 12% of patients given 100 mg/m2but was very uncommon in patients given 60 mg/m2.
Hematologic responses, febrile reactions and infections, and rates of septic death for different regimens are dose related [
see Adverse Reactions (6.1), Clinical Studies (14)].Three breast cancer patients with severe liver impairment (bilirubin >1.7 times ULN) developed fatal gastrointestinal bleeding associated with severe drug-induced thrombocytopenia. In gastric cancer patients treated with docetaxel in combination with cisplatin and fluorouracil (TCF), febrile neutropenia and/or neutropenic infection occurred in 12% of patients receiving G-CSF compared to 28% who did not. Patients receiving TCF should be closely monitored during the first and subsequent cycles for febrile neutropenia and neutropenic infection [
see Dosage and Administration (2.7), Adverse Reactions (6)].• a history of severe hypersensitivity reactions to docetaxel or to other drugs formulated with polysorbate 80. Severe reactions, including anaphylaxis, have occurred [see].5.5 Hypersensitivity ReactionsMonitor patients closely for hypersensitivity reactions, especially during the first and second infusions. Severe hypersensitivity reactions characterized by generalized rash/erythema, hypotension and/or bronchospasm, or fatal anaphylaxis, have been reported in patients premedicated with 3 days of corticosteroids. Severe hypersensitivity reactions require immediate discontinuation of the Docetaxel Injection infusion and aggressive therapy. Do not rechallenge patients with a history of severe hypersensitivity reactions with Docetaxel Injection [
see Contraindications (4)].Patients who have previously experienced a hypersensitivity reaction to paclitaxel may develop a hypersensitivity reaction to docetaxel that may include severe or fatal reactions such as anaphylaxis. Monitor patients with a previous history of hypersensitivity to paclitaxel closely during initiation of docetaxel therapy. Hypersensitivity reactions may occur within a few minutes following initiation of a Docetaxel Injection infusion. If minor reactions such as flushing or localized skin reactions occur, interruption of therapy is not required. All patients should be premedicated with an oral corticosteroid prior to the initiation of the infusion of Docetaxel Injection [
see Dosage and Administration (2.6)].