Sorry, you need to enable JavaScript to visit this website.

DOCETAXEL INJECTION, SOLUTION (docetaxel injection, USP) Adverse Reactions

6 ADVERSE REACTIONS

The most serious adverse reactions from docetaxel are:

The most common adverse reactions across all docetaxel indications are infections, neutropenia, anemia, febrile neutropenia, hypersensitivity, thrombocytopenia, neuropathy, dysgeusia, dyspnea, constipation, anorexia, nail disorders, fluid retention, asthenia, pain, nausea, diarrhea, vomiting, mucositis, alopecia, skin reactions, and myalgia. Incidence varies depending on the indication.

Adverse reactions are described according to indication. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Responding patients may not experience an improvement in performance status on therapy and may experience worsening. The relationship between changes in performance status, response to therapy, and treatment-related side effects has not been established.

6.1 Clinical Trials Experience

Breast Cancer

Monotherapy with Docetaxel for Locally Advanced or Metastatic Breast Cancer after Failure of Prior Chemotherapy

Docetaxel 100 mg/m2: Adverse drug reactions occurring in at least 5% of patients are compared for three populations who received docetaxel administered at 100 mg/m2 as a 1-hour infusion every 3 weeks: 2045 patients with various tumor types and normal baseline liver function tests; the subset of 965 patients with locally advanced or metastatic breast cancer, both previously treated and untreated with chemotherapy, who had normal baseline liver function tests; and an additional 61 patients with various tumor types who had abnormal liver function tests at baseline. These reactions were described using COSTART terms and were considered possibly or probably related to docetaxel. At least 95% of these patients did not receive hematopoietic support. The safety profile is generally similar in patients receiving docetaxel for the treatment of breast cancer and in patients with other tumor types (see Table 3).

Table 3: Summary of Adverse Reactions in Patients Receiving Docetaxel at 100 mg/m2
Adverse Reaction All Tumor Types
Normal LFTs*
n=2045
%
All Tumor Types
Elevated LFTs
n=61
%
Breast Cancer
Normal LFTs*
n=965
%
*
Normal Baseline LFTs: Transaminases ≤1.5 times ULN or alkaline phosphatase ≤2.5 times ULN or isolated elevations of transaminases or alkaline phosphatase up to 5 times ULN
Elevated Baseline LFTs: AST and/or ALT >1.5 times ULN concurrent with alkaline phosphatase >2.5 times ULN
Febrile Neutropenia: ANC grade 4 with fever >38°C with intravenous antibiotics and/or hospitalization
Hematologic
Neutropenia
  <2000 cells/mm3 96 96 99
  <500 cells/mm3 75 88 86
Leukopenia
  <4000 cells/mm3 96 98 99
  <1000 cells/mm3 32 47 44
Thrombocytopenia
  <100,000 cells/mm3 8 25 9
Anemia
  <11 g/dL 90 92 94
  <8 g/dL 9 31 8
Febrile Neutropenia 11 26 12
Septic Death 2 5 1
Non-Septic Death 1 7 1
Infections
  Any 22 33 22
  Severe 6 16 6
Fever in Absence of Infection
  Any 31 41 35
  Severe 2 8 2
Hypersensitivity Reactions
Regardless of Premedication
  Any 21 20 18
  Severe 4 10 3
With 3-day Premedication n=92 n=3 n=92
  Any 15 33 15
  Severe 2 0 2
Fluid Retention
Regardless of Premedication
  Any 47 39 60
  Severe 7 8 9
With 3-day Premedication n=92 n=3 n=92
  Any 64 67 64
  Severe 7 33 7
Neurosensory
  Any 49 34 58
  Severe 4 0 6
Cutaneous
  Any 48 54 47
  Severe 5 10 5
Nail Changes
  Any 31 23 41
  Severe 3 5 4
Gastrointestinal
Nausea 39 38 42
Vomiting 22 23 23
Diarrhea 39 33 43
  Severe 5 5 6
Stomatitis
  Any 42 49 52
  Severe 6 13 7
Alopecia 76 62 74
Asthenia
  Any 62 53 66
  Severe 13 25 15
Myalgia
  Any 19 16 21
  Severe 2 2 2
Arthralgia 9 7 8
Infusion Site Reactions 4 3 4

Hematologic Reactions

Reversible marrow suppression was the major dose-limiting toxicity of docetaxel [see Warnings and Precautions (5.3)]. The median time to nadir was 7 days, while the median duration of severe neutropenia (<500 cells/mm3) was 7 days. Among 2045 patients with solid tumors and normal baseline LFTs, severe neutropenia occurred in 75.4% and lasted for more than 7 days in 2.9% of cycles.

Febrile neutropenia (<500 cells/mm3 with fever >38°C with intravenous antibiotics and/or hospitalization) occurred in 11% of patients with solid tumors, in 12.3% of patients with metastatic breast cancer, and in 9.8% of 92 breast cancer patients premedicated with 3-day corticosteroids.

Severe infectious episodes occurred in 6.1% of patients with solid tumors, in 6.4% of patients with metastatic breast cancer, and in 5.4% of 92 breast cancer patients premedicated with 3-day corticosteroids.

Thrombocytopenia (<100,000 cells/mm3) associated with fatal gastrointestinal hemorrhage has been reported.

Hypersensitivity Reactions

Severe hypersensitivity reactions have been reported [see Boxed Warning, Warnings and Precautions (5.5)]. Minor events, including flushing, rash with or without pruritus, chest tightness, back pain, dyspnea, drug fever, or chills, have been reported and resolved after discontinuing the infusion and instituting appropriate therapy.

Fluid Retention

Fluid retention can occur with the use of docetaxel [see Boxed Warning, Dosage and Administration (2.6), Warnings and Precautions (5.6)].

Cutaneous Reactions

Severe skin toxicity is discussed elsewhere in the label [see Warnings and Precautions (5.8)]. Reversible cutaneous reactions characterized by a rash including localized eruptions, mainly on the feet and/or hands, but also on the arms, face, or thorax, usually associated with pruritus, have been observed. Eruptions generally occurred within 1 week after docetaxel infusion, recovered before the next infusion, and were not disabling.

Severe nail disorders were characterized by hypo- or hyperpigmentation, and occasionally by onycholysis (in 0.8% of patients with solid tumors) and pain.

Neurologic Reactions

Neurologic reactions are discussed elsewhere in the label [see Warnings and Precautions (5.9)].

Gastrointestinal Reactions

Nausea, vomiting, and diarrhea were generally mild to moderate. Severe reactions occurred in 3%–5% of patients with solid tumors and to a similar extent among metastatic breast cancer patients. The incidence of severe reactions was 1% or less for the 92 breast cancer patients premedicated with 3-day corticosteroids.

Severe stomatitis occurred in 5.5% of patients with solid tumors, in 7.4% of patients with metastatic breast cancer, and in 1.1% of the 92 breast cancer patients premedicated with 3-day corticosteroids.

Cardiovascular Reactions

Hypotension occurred in 2.8% of patients with solid tumors; 1.2% required treatment. Clinically meaningful events such as heart failure, sinus tachycardia, atrial flutter, dysrhythmia, unstable angina, pulmonary edema, and hypertension have occurred. Seven of 86 (8.1%) of metastatic breast cancer patients receiving docetaxel 100 mg/m2 in a randomized trial and who had serial left ventricular ejection fractions assessed developed deterioration of LVEF by ≥10% associated with a drop below the institutional lower limit of normal.

Infusion Site Reactions

Infusion site reactions were generally mild and consisted of hyperpigmentation, inflammation, redness or dryness of the skin, phlebitis, extravasation, or swelling of the vein.

Hepatic Reactions

In patients with normal LFTs at baseline, bilirubin values greater than the ULN occurred in 8.9% of patients. Increases in AST or ALT >1.5 times the ULN, or alkaline phosphatase >2.5 times ULN, were observed in 18.9% and 7.3% of patients, respectively. While on docetaxel, increases in AST and/or ALT >1.5 times ULN concomitant with alkaline phosphatase >2.5 times ULN occurred in 4.3% of patients with normal LFTs at baseline. Whether these changes were related to the drug or underlying disease has not been established.

Hematologic and Other Toxicity: Relation to Dose and Baseline Liver Chemistry Abnormalities

Hematologic and other toxicity is increased at higher doses and in patients with elevated baseline liver function tests (LFTs). In the following tables, adverse drug reactions are compared for three populations: 730 patients with normal LFTs given docetaxel at 100 mg/m2 in the randomized and single arm studies of metastatic breast cancer after failure of previous chemotherapy; 18 patients in these studies who had abnormal baseline LFTs (defined as AST and/or ALT >1.5 times ULN concurrent with alkaline phosphatase >2.5 times ULN); and 174 patients in Japanese studies given docetaxel at 60 mg/m2 who had normal LFTs (see Tables 4 and 5).

Table 4: Hematologic Adverse Reactions in Breast Cancer Patients Previously Treated with Chemotherapy Treated at Docetaxel 100 mg/m2 with Normal or Elevated Liver Function Tests or 60 mg/m2 with Normal Liver Function Tests
Docetaxel
100 mg/m2
Docetaxel
60 mg/m2
Adverse Reaction Normal LFTs*
n=730
%
Elevated LFTs
n=18
%
Normal LFTs*
n=174
%
*
Normal Baseline LFTs: Transaminases ≤1.5 times ULN or alkaline phosphatase ≤2.5 times ULN or isolated elevations of transaminases or alkaline phosphatase up to 5 times ULN
Elevated Baseline LFTs: AST and/or ALT >1.5 times ULN concurrent with alkaline phosphatase >2.5 times ULN
Incidence of infection requiring hospitalization and/or intravenous antibiotics was 8.5% (n=62) among the 730 patients with normal LFTs at baseline; 7 patients had concurrent grade 3 neutropenia, and 46 patients had grade 4 neutropenia.
§
Febrile Neutropenia: For 100 mg/m2, ANC grade 4 and fever >38°C with intravenous antibiotics and/or hospitalization; for 60 mg/m2, ANC grade 3/4 and fever >38.1°C
Neutropenia
  Any <2000 cells/mm3 98 100 95
  Grade 4 <500 cells/mm3 84 94 75
Thrombocytopenia
  Any <100,000 cells/mm3 11 44 14
  Grade 4 <20,000 cells/mm3 1 17 1
Anemia <11 g/dL 95 94 65
Infection
  Any 23 39 1
  Grade 3 and 4 7 33 0
Febrile Neutropenia§
  By Patient 12 33 0
  By Course 2 9 0
Septic Death 2 6 1
Non-Septic Death 1 11 0
Table 5: Non-Hematologic Adverse Reactions in Breast Cancer Patients Previously Treated with Chemotherapy Treated at Docetaxel 100 mg/m2 with Normal or Elevated Liver Function Tests or 60 mg/m2 with Normal Liver Function Tests
Docetaxel
100 mg/m2
Docetaxel
60 mg/m2
Adverse Reaction Normal LFTs*
n=730
%
Elevated LFTs
n=18
%
Normal LFTs*
n=174
%
NA = not available
*
Normal Baseline LFTs: Transaminases ≤1.5 times ULN or alkaline phosphatase ≤2.5 times ULN or isolated elevations of transaminases or alkaline phosphatase up to 5 times ULN
Elevated Baseline Liver Function: AST and/or ALT >1.5 times ULN concurrent with alkaline phosphatase >2.5 times ULN
Fluid Retention includes (by COSTART): edema (peripheral, localized, generalized, lymphedema, pulmonary edema, and edema otherwise not specified) and effusion (pleural, pericardial, and ascites); no premedication given with the 60 mg/m2 dose
Acute Hypersensitivity Reaction
Regardless of Premedication
  Any 13 6 1
  Severe 1 0 0
Fluid Retention
Regardless of Premedication
  Any 56 61 13
  Severe 8 17 0
Neurosensory
  Any 57 50 20
  Severe 6 0 0
Myalgia 23 33 3
Cutaneous
  Any 45 61 31
  Severe 5 17 0
Asthenia
  Any 65 44 66
  Severe 17 22 0
Diarrhea
  Any 42 28 NA
  Severe 6 11
Stomatitis
  Any 53 67 19
  Severe 8 39 1

In the three-arm monotherapy trial, TAX313, which compared docetaxel 60 mg/m2, 75 mg/m2 and 100 mg/m2 in advanced breast cancer, grade 3/4 or severe adverse reactions occurred in 49.0% of patients treated with docetaxel 60 mg/m2 compared to 55.3% and 65.9% treated with 75 mg/m2 and 100 mg/m2, respectively. Discontinuation due to adverse reactions was reported in 5.3% of patients treated with 60 mg/m2 versus 6.9% and 16.5% for patients treated at 75 mg/m2 and 100 mg/m2, respectively. Deaths within 30 days of last treatment occurred in 4.0% of patients treated with 60 mg/m2 compared to 5.3% and 1.6% for patients treated at 75 mg/m2 and 100 mg/m2, respectively.

The following adverse reactions were associated with increasing docetaxel doses: fluid retention (26%, 38%, and 46% at 60 mg/m2, 75 mg/m2, and 100 mg/m2, respectively), thrombocytopenia (7%, 11% and 12%, respectively), neutropenia (92%, 94%, and 97%, respectively), febrile neutropenia (5%, 7%, and 14%, respectively), treatment-related grade 3/4 infection (2%, 3%, and 7%, respectively) and anemia (87%, 94%, and 97%, respectively).

Combination Therapy with Docetaxel in the Adjuvant Treatment of Breast Cancer

The following table presents treatment-emergent adverse reactions observed in 744 patients, who were treated with docetaxel 75 mg/m2 every 3 weeks in combination with doxorubicin and cyclophosphamide (see Table 6).

Table 6: Clinically Important Treatment-Emergent Adverse Reactions Regardless of Causal Relationship in Patients Receiving Docetaxel in Combination with Doxorubicin and Cyclophosphamide (TAX316)
Docetaxel 75 mg/m2 + Doxorubicin 50 mg/m2 + Cyclophosphamide 500 mg/m2 (TAC)
n=744
%
Fluorouracil 500 mg/m2 + Doxorubicin 50 mg/m2 + Cyclophosphamide 500 mg/m2 (FAC)
n=736
%
Adverse Reaction Any Grade 3/4 Any Grade 3/4
*
COSTART term and grading system for events related to treatment.
Anemia 92 4 72 2
Neutropenia 71 66 82 49
Fever in absence of infection 47 1 17 0
Infection 39 4 36 2
Thrombocytopenia 39 2 28 1
Febrile neutropenia 25 N/A 3 N/A
Neutropenic infection 12 N/A 6 N/A
Hypersensitivity reactions 13 1 4 0
Lymphedema 4 0 1 0
Fluid Retention* 35 1 15 0
Peripheral edema 27 0 7 0
Weight gain 13 0 9 0
Neuropathy sensory 26 0 10 0
Neuro-cortical 5 1 6 1
Neuropathy motor 4 0 2 0
Neuro-cerebellar 2 0 2 0
Syncope 2 1 1 0
Alopecia 98 N/A 97 N/A
Skin toxicity 27 1 18 0
Nail disorders 19 0 14 0
Nausea 81 5 88 10
Stomatitis 69 7 53 2
Vomiting 45 4 59 7
Diarrhea 35 4 28 2
Constipation 34 1 32 1
Taste perversion 28 1 15 0
Anorexia 22 2 18 1
Abdominal Pain 11 1 5 0
Amenorrhea 62 N/A 52 N/A
Cough 14 0 10 0
Cardiac dysrhythmias 8 0 6 0
Vasodilatation 27 1 21 1
Hypotension 2 0 1 0
Phlebitis 1 0 1 0
Asthenia 81 11 71 6
Myalgia 27 1 10 0
Arthralgia 19 1 9 0
Lacrimation disorder 11 0 7 0
Conjunctivitis 5 0 7 0

Of the 744 patients treated with TAC, 36.3% experienced severe treatment-emergent adverse reactions compared to 26.6% of the 736 patients treated with FAC. Dose reductions due to hematologic toxicity occurred in 1% of cycles in the TAC arm versus 0.1% of cycles in the FAC arm. Six percent of patients treated with TAC discontinued treatment due to adverse reactions, compared to 1.1% treated with FAC; fever in the absence of infection and allergy being the most common reasons for withdrawal among TAC-treated patients. Two patients died in each arm within 30 days of their last study treatment; 1 death per arm was attributed to study drugs.

Fever and Infection

During the treatment period, fever in the absence of infection was seen in 46.5% of TAC-treated patients and in 17.1% of FAC-treated patients. Grade 3/4 fever in the absence of infection was seen in 1.3% and 0% of TAC- and FAC-treated patients, respectively. Infection was seen in 39.4% of TAC-treated patients compared to 36.3% of FAC-treated patients. Grade 3/4 infection was seen in 3.9% and 2.2% of TAC-treated and FAC-treated patients, respectively. There were no septic deaths in either treatment arm during the treatment period.

Gastrointestinal Reactions

In addition to gastrointestinal reactions reflected in the table above, 7 patients in the TAC arm were reported to have colitis/enteritis/large intestine perforation versus one patient in the FAC arm. Five of the 7 TAC-treated patients required treatment discontinuation; no deaths due to these events occurred during the treatment period.

Cardiovascular Reactions

More cardiovascular reactions were reported in the TAC arm versus the FAC arm during the treatment period: arrhythmias, all grades (6.2% vs. 4.9%), and hypotension, all grades (1.9% vs. 0.8%). Twenty-six (26) patients (3.5%) in the TAC arm and 17 patients (2.3%) in the FAC arm developed CHF during the study period. All except one patient in each arm were diagnosed with CHF during the follow-up period. Two (2) patients in TAC arm and 4 patients in FAC arm died due to CHF. The risk of CHF was higher in the TAC arm in the first year, and then was similar in both treatment arms.

Adverse Reactions during the Follow-Up Period (Median Follow-Up Time of 8 Years)

In study TAX316, the most common adverse reactions that started during the treatment period and persisted into the follow-up period in TAC and FAC patients are described below (median follow-up time of 8 years).

Nervous System Disorders: In study TAX316, peripheral sensory neuropathy started during the treatment period and persisted into the follow-up period in 84 patients (11.3%) in TAC arm and 15 patients (2%) in FAC arm. At the end of the follow-up period (median follow-up time of 8 years), peripheral sensory neuropathy was observed to be ongoing in 10 patients (1.3%) in TAC arm, and in 2 patients (0.3%) in FAC arm.

Skin and Subcutaneous Tissue Disorders: In study TAX316, alopecia persisting into the follow-up period after the end of chemotherapy was reported in 687 of 744 TAC patients (92.3%) and 645 of 736 FAC patients (87.6%). At the end of the follow-up period (actual median follow-up time of 8 years), alopecia was observed to be ongoing in 29 TAC patients (3.9%) and 16 FAC patients (2.2%).

Reproductive System and Breast Disorders: In study TAX316, amenorrhea that started during the treatment period and persisted into the follow-up period after the end of chemotherapy was reported in 202 of 744 TAC patients (27.2%) and 125 of 736 FAC patients (17.0%). Amenorrhea was observed to be ongoing at the end of the follow-up period (median follow-up time of 8 years) in 121 of 744 TAC patients (16.3%) and 86 FAC patients (11.7%).

General Disorders and Administration Site Conditions: In study TAX316, peripheral edema that started during the treatment period and persisted into the follow-up period after the end of chemotherapy was observed in 119 of 744 TAC patients (16.0%) and 23 of 736 FAC patients (3.1%). At the end of the follow-up period (actual median follow-up time of 8 years), peripheral edema was ongoing in 19 TAC patients (2.6%) and 4 FAC patients (0.5%).

In study TAX316, lymphedema that started during the treatment period and persisted into the follow-up period after the end of chemotherapy was reported in 11 of 744 TAC patients (1.5%) and 1 of 736 FAC patients (0.1%). At the end of the follow-up period (actual median follow-up time of 8 years), lymphedema was observed to be ongoing in 6 TAC patients (0.8%) and 1 FAC patient (0.1%).

In study TAX316, asthenia that started during the treatment period and persisted into the follow-up period after the end of chemotherapy was reported in 236 of 744 TAC patients (31.7%) and 180 of 736 FAC patients (24.5%). At the end of the follow-up period (actual median follow-up time of 8 years), asthenia was observed to be ongoing in 29 TAC patients (3.9%) and 16 FAC patients (2.2%).

Acute Myeloid Leukemia (AML)/Myelodysplastic Syndrome (MDS): AML occurred in the adjuvant breast cancer trial (TAX316). The cumulative risk of developing treatment-related AML at median follow-up time of 8 years in TAX316 was 0.4% for TAC-treated patients and 0.1% for FAC-treated patients. One TAC patient (0.1%) and 1 FAC patient (0.1%) died due to AML during the follow-up period (median follow-up time of 8 years).

Myelodysplastic syndrome occurred in 2 of 744 (0.3%) patients who received TAC and in 1 of 736 (0.1%) patients who received FAC. AML occurs at a higher frequency when these agents are given in combination with radiation therapy.

Lung Cancer

Monotherapy with Docetaxel for Unresectable, Locally Advanced or Metastatic NSCLC Previously Treated with Platinum-Based Chemotherapy

Docetaxel 75 mg/m2: Treatment-emergent adverse drug reactions are shown in Table 7. Included in this table are safety data for a total of 176 patients with non-small cell lung carcinoma and a history of prior treatment with platinum-based chemotherapy who were treated in two randomized, controlled trials. These reactions were described using NCI Common Toxicity Criteria regardless of relationship to study treatment, except for the hematologic toxicities or where otherwise noted.

Table 7: Treatment-Emergent Adverse Reactions Regardless of Relationship to Treatment in Patients Receiving Docetaxel as Monotherapy for Non-small Cell Lung Cancer Previously Treated with Platinum-Based Chemotherapy*
Adverse Reaction Docetaxel 75 mg/m2
n=176
%
Best Supportive Care
n=49
%
Vinorelbine/Ifosfamide
n=119
%
*
Normal Baseline LFTs: Transaminases ≤1.5 times ULN or alkaline phosphatase ≤2.5 times ULN or isolated elevations of transaminases or alkaline phosphatase up to 5 times ULN
Febrile Neutropenia: ANC grade 4 with fever >38°C with intravenous antibiotics and/or hospitalization
Not Applicable
§
Not Done
COSTART term and grading system
Neutropenia
  Any 84 14 83
  Grade 3/4 65 12 57
Leukopenia
  Any 84 6 89
  Grade 3/4 49 0 43
Thrombocytopenia
  Any 8 0 8
  Grade 3/4 3 0 2
Anemia
  Any 91 55 91
  Grade 3/4 9 12 14
Febrile Neutropenia 6 NA 1
Infection
  Any 34 29 30
  Grade 3/4 10 6 9
Treatment Related Mortality 3 NA 3
Hypersensitivity Reactions
  Any 6 0 1
  Grade 3/4 3 0 0
Fluid Retention
  Any 34 ND§ 23
  Severe 3 3
Neurosensory
  Any 23 14 29
  Grade 3/4 2 6 5
Neuromotor
  Any 16 8 10
  Grade 3/4 5 6 3
Skin
  Any 20 6 17
  Grade 3/4 1 2 1
Gastrointestinal
Nausea
  Any 34 31 31
  Grade 3/4 5 4 8
Vomiting
  Any 22 27 22
  Grade 3/4 3 2 6
Diarrhea
  Any 23 6 12
  Grade 3/4 3 0 4
Alopecia 56 35 50
Asthenia
  Any 53 57 54
  Severe 18 39 23
Stomatitis
  Any 26 6 8
  Grade 3/4 2 0 1
Pulmonary
  Any 41 49 45
  Grade 3/4 21 29 19
Nail Disorder
  Any 11 0 2
  Severe 1 0 0
Myalgia
  Any 6 0 3
  Severe 0 0 0
Arthralgia
  Any 3 2 2
  Severe 0 0 1
Taste Perversion
  Any 6 0 0
  Severe 1 0 0

Combination Therapy with Docetaxel in Chemotherapy-Naïve Advanced Unresectable or Metastatic NSCLC

Table 8 presents safety data from two arms of an open label, randomized controlled trial (TAX326) that enrolled patients with unresectable stage IIIB or IV non-small cell lung cancer and no history of prior chemotherapy. Adverse reactions were described using the NCI Common Toxicity Criteria except where otherwise noted.

Table 8: Adverse Reactions Regardless of Relationship to Treatment in Chemotherapy-Naïve Advanced Non-small Cell Lung Cancer Patients Receiving Docetaxel in Combination with Cisplatin
Adverse Reaction Docetaxel 75 mg/m2 + Cisplatin 75 mg/m2
n=406
%
Vinorelbine 25 mg/m2 + Cisplatin 100 mg/m2
n=396
%
*
Replaces NCI term "Allergy"
COSTART term and grading system
Neutropenia
  Any 91 90
  Grade 3/4 74 78
Febrile Neutropenia 5 5
Thrombocytopenia
  Any 15 15
  Grade 3/4 3 4
Anemia
  Any 89 94
  Grade 3/4 7 25
Infection
  Any 35 37
  Grade 3/4 8 8
Fever in absence of infection
  Any 33 29
  Grade 3/4 <1 1
Hypersensitivity Reaction*
  Any 12 4
  Grade 3/4 3 <1
Fluid Retention
  Any 54 42
  All severe or life-threatening events   2 2
Pleural effusion
  Any 23 22
  All severe or life-threatening events 2 2
Peripheral edema
  Any 34 18
  All severe or life-threatening events <1 <1
Weight gain
  Any 15 9
  All severe or life-threatening events <1 <1
Neurosensory
  Any 47 42
  Grade 3/4 4 4
Neuromotor
  Any 19 17
  Grade 3/4 3 6
Skin
  Any 16 14
  Grade 3/4 <1 1
Nausea
  Any 72 76
  Grade 3/4 10 17
Vomiting
  Any 55 61
  Grade 3/4 8 16
Diarrhea
  Any 47 25
  Grade 3/4 7 3
Anorexia
  Any 42 40
  All severe or life-threatening events 5 5
Stomatitis
  Any 24 21
  Grade 3/4 2 1
Alopecia
  Any 75 42
  Grade 3 <1 0
Asthenia
  Any 74 75
  All severe or life-threatening events 12 14
Nail Disorder
  Any 14 <1
  All severe events <1 0
Myalgia
  Any 18 12
  All severe events <1 <1

Deaths within 30 days of last study treatment occurred in 31 patients (7.6%) in the docetaxel+cisplatin arm and 37 patients (9.3%) in the vinorelbine+cisplatin arm. Deaths within 30 days of last study treatment attributed to study drug occurred in 9 patients (2.2%) in the docetaxel+cisplatin arm and 8 patients (2.0%) in the vinorelbine+cisplatin arm.

The second comparison in the study, vinorelbine+cisplatin versus docetaxel+carboplatin (which did not demonstrate a superior survival associated with docetaxel, [see Clinical Studies (14.3)]) demonstrated a higher incidence of thrombocytopenia, diarrhea, fluid retention, hypersensitivity reactions, skin toxicity, alopecia and nail changes on the docetaxel+carboplatin arm, while a higher incidence of anemia, neurosensory toxicity, nausea, vomiting, anorexia and asthenia was observed on the vinorelbine+cisplatin arm.

Prostate Cancer

Combination Therapy with Docetaxel in Patients with Prostate Cancer

The following data are based on the experience of 332 patients, who were treated with docetaxel 75 mg/m2 every 3 weeks in combination with prednisone 5 mg orally twice daily (see Table 9).

Table 9: Clinically Important Treatment-Emergent Adverse Reactions (Regardless of Relationship) in Patients with Prostate Cancer who Received Docetaxel in Combination with Prednisone (TAX327)
Docetaxel 75 mg/m2 every 3 weeks + prednisone
5 mg twice daily
n=332
%
Mitoxantrone 12 mg/m2 every 3 weeks + prednisone
5 mg twice daily
n=335
%
Adverse Reaction Any Grade 3/4 Any Grade 3/4
*
Related to treatment
Anemia 67 5 58 2
Neutropenia 41 32 48 22
Thrombocytopenia 3 1 8 1
Febrile Neutropenia 3 N/A 2 N/A
Infection 32 6 20 4
Epistaxis 6 0 2 0
Allergic Reactions 8 1 1 0
Fluid Retention* 24 1 5 0
Weight Gain* 8 0 3 0
Peripheral Edema* 18 0 2 0
Neuropathy Sensory 30 2 7 0
Neuropathy Motor 7 2 3 1
Rash/Desquamation 6 0 3 1
Alopecia 65 N/A 13 N/A
Nail Changes 30 0 8 0
Nausea 41 3 36 2
Diarrhea 32 2 10 1
Stomatitis/Pharyngitis 20 1 8 0
Taste Disturbance 18 0 7 0
Vomiting 17 2 14 2
Anorexia 17 1 14 0
Cough 12 0 8 0
Dyspnea 15 3 9 1
Cardiac left ventricular function 10 0 22 1
Fatigue 53 5 35 5
Myalgia 15 0 13 1
Tearing 10 1 2 0
Arthralgia 8 1 5 1

Gastric Cancer

Combination Therapy with Docetaxel Injection in Gastric Adenocarcinoma

Data in the following table are based on the experience of 221 patients with advanced gastric adenocarcinoma and no history of prior chemotherapy for advanced disease who were treated with Docetaxel Injection 75 mg/m2 in combination with cisplatin and fluorouracil (see Table 10).

Table 10: Clinically Important Treatment-Emergent Adverse Reactions Regardless of Relationship to Treatment in the Gastric Cancer Study
Docetaxel Injection 75 mg/m2 + cisplatin 75 mg/m2 + fluorouracil 750 mg/m2
n=221
Cisplatin 100 mg/m2 + fluorouracil 1000 mg/m2
n=224
Adverse Reaction Any % Grade 3/4 % Any % Grade 3/4 %
Clinically important treatment-emergent adverse reactions were determined based upon frequency, severity, and clinical impact of the adverse reaction.
*
Related to treatment
Anemia 97 18 93 26
Neutropenia 96 82 83 57
Fever in the absence of infection 36 2 23 1
Thrombocytopenia 26 8 39 14
Infection 29 16 23 10
Febrile neutropenia 16 N/A 5 N/A
Neutropenic infection 16 N/A 10 N/A
Allergic reactions 10 2 6 0
Fluid retention* 15 0 4 0
Edema* 13 0 3 0
Lethargy 63 21 58 18
Neurosensory 38 8 25 3
Neuromotor 9 3 8 3
Dizziness 16 5 8 2
Alopecia 67 5 41 1
Rash/itch 12 1 9 0
Nail changes 8 0 0 0
Skin desquamation 2 0 0 0
Nausea 73 16 76 19
Vomiting 67 15 73 19
Anorexia 51 13 54 12
Stomatitis 59 21 61 27
Diarrhea 78 20 50 8
Constipation 25 2 34 3
Esophagitis/dysphagia/odynophagia 16 2 14 5
Gastrointestinal pain/cramping 11 2 7 3
Cardiac dysrhythmias 5 2 2 1
Myocardial ischemia 1 0 3 2
Tearing 8 0 2 0
Altered hearing 6 0 13 2

Head and Neck Cancer

Combination Therapy with Docetaxel Injection in Head and Neck Cancer

Table 11 summarizes the safety data obtained from patients that received induction chemotherapy with Docetaxel Injection 75 mg/m2 in combination with cisplatin and fluorouracil followed by radiotherapy (TAX323; 174 patients) or chemoradiotherapy (TAX324; 251 patients). The treatment regimens are described in Section 14.6.

Table 11: Clinically Important Treatment-Emergent Adverse Reactions (Regardless of Relationship) in Patients with SCCHN Receiving Induction Chemotherapy with Docetaxel Injection in Combination with Cisplatin and Fluorouracil Followed by Radiotherapy (TAX323) or Chemoradiotherapy (TAX324)
TAX323 (n=355) TAX324 (n=494)
Docetaxel Injection arm (n=174) Comparator arm (n=181) Docetaxel Injection arm (n=251) Comparator arm (n=243)
Adverse Reaction (by Body System) Any
%
Grade 3/4
%
Any
%
Grade 3/4
%
Any
%
Grade 3/4
%
Any
%
Grade 3/4
%
Clinically important treatment-emergent adverse reactions based upon frequency, severity, and clinical impact.
*
Febrile neutropenia: grade ≥2 fever concomitant with grade 4 neutropenia requiring intravenous antibiotics and/or hospitalization
Related to treatment
Includes superficial and deep vein thrombosis and pulmonary embolism
Neutropenia 93 76 87 53 95 84 84 56
Anemia 89 9 88 14 90 12 86 10
Thrombocytopenia 24 5 47 18 28 4 31 11
Infection 27 9 26 8 23 6 28 5
Febrile neutropenia* 5 N/A 2 N/A 12 N/A 7 N/A
Neutropenic infection 14 N/A 8 N/A 12 N/A 8 N/A
Cancer pain 21 5 16 3 17 9 20 11
Lethargy 41 3 38 3 61 5 56 10
Fever in the absence of infection 32 1 37 0 30 4 28 3
Myalgia 10 1 7 0 7 0 7 2
Weight loss 21 1 27 1 14 2 14 2
Allergy 6 0 3 0 2 0 0 0
Fluid retention 20 0 14 1 13 1 7 2
Edema only 13 0 7 0 12 1 6 1
Weight gain only 6 0 6 0 0 0 1 0
Dizziness 2 0 5 1 16 4 15 2
Neurosensory 18 1 11 1 14 1 14 0
Altered hearing 6 0 10 3 13 1 19 3
Neuromotor 2 1 4 1 9 0 10 2
Alopecia 81 11 43 0 68 4 44 1
Rash/itch 12 0 6 0 20 0 16 1
Dry skin 6 0 2 0 5 0 3 0
Desquamation 4 1 6 0 2 0 5 0
Nausea 47 1 51 7 77 14 80 14
Stomatitis 43 4 47 11 66 21 68 27
Vomiting 26 1 39 5 56 8 63 10
Diarrhea 33 3 24 4 48 7 40 3
Constipation 17 1 16 1 27 1 38 1
Anorexia 16 1 25 3 40 12 34 12
Esophagitis/dysphagia/Odynophagia 13 1 18 3 25 13 26 10
Taste, sense of smell altered 10 0 5 0 20 0 17 1
Gastrointestinal pain/cramping 8 1 9 1 15 5 10 2
Heartburn 6 0 6 0 13 2 13 1
Gastrointestinal bleeding 4 2 0 0 5 1 2 1
Cardiac dysrhythmia 2 2 2 1 6 3 5 3
Venous 3 2 6 2 4 2 5 4
Ischemia myocardial 2 2 1 0 2 1 1 1
Tearing 2 0 1 0 2 0 2 0
Conjunctivitis 1 0 1 0 1 0 0.4 0

6.2 Postmarketing Experience

The following adverse reactions have been identified from clinical trials and/or postmarketing surveillance. Because these reactions are reported from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Body as a whole: diffuse pain, chest pain, radiation recall phenomenon, injection site recall reaction (recurrence of skin reaction at a site of previous extravasation following administration of docetaxel at a different site) at the site of previous extravasation.

Cardiovascular: atrial fibrillation, deep vein thrombosis, ECG abnormalities, thrombophlebitis, pulmonary embolism, syncope, tachycardia, myocardial infarction. Ventricular arrhythmia, including ventricular tachycardia, in patients treated with docetaxel in combination regimens including doxorubicin, 5-fluorouracil and/or cyclophosphamide may be associated with fatal outcome.

Cutaneous: cutaneous lupus erythematosus, bullous eruptions such as erythema multiforme and severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome, toxic epidermal necrolysis and acute generalized exanthematous pustulosis, scleroderma-like changes (usually preceded by peripheral lymphedema), severe palmar-plantar erythrodysesthesia, and permanent alopecia.

Gastrointestinal: enterocolitis, including colitis, ischemic colitis, and neutropenic enterocolitis, which may be fatal. Abdominal pain, anorexia, constipation, duodenal ulcer, esophagitis, gastrointestinal hemorrhage, gastrointestinal perforation, intestinal obstruction, ileus, and dehydration as a consequence of gastrointestinal events.

Hearing: ototoxicity, hearing disorders and/or hearing loss, including during use with other ototoxic drugs.

Hematologic: bleeding episodes, disseminated intravascular coagulation (DIC), often in association with sepsis or multiorgan failure.

Hepatic: hepatitis, sometimes fatal, primarily in patients with pre-existing liver disorders.

Hypersensitivity: anaphylactic shock with fatal outcome in patients who received premedication. Severe hypersensitivity reactions with fatal outcome with docetaxel in patients who previously experienced hypersensitivity reactions to paclitaxel.

Metabolism and Nutrition Disorders: electrolyte imbalance, including hyponatremia, hypokalemia, hypomagnesemia, and hypocalcemia. Tumor lysis syndrome, sometimes fatal.

Neurologic: confusion, seizures or transient loss of consciousness, sometimes appearing during the infusion of the drug.

Ophthalmologic: conjunctivitis, lacrimation or lacrimation with or without conjunctivitis, cystoid macular edema (CME). Excessive tearing which may be attributable to lacrimal duct obstruction. Transient visual disturbances (flashes, flashing lights, scotomata), typically occurring during drug infusion and reversible upon discontinuation of the infusion, in association with hypersensitivity reactions.

Respiratory: dyspnea, acute pulmonary edema, acute respiratory distress syndrome/pneumonitis, interstitial lung disease, interstitial pneumonia, respiratory failure, and pulmonary fibrosis, which may be fatal. Radiation pneumonitis in patients receiving concomitant radiotherapy.

Renal: renal insufficiency and renal failure, the majority of cases were associated with concomitant nephrotoxic drugs.

Second Primary Malignancies: second primary malignancies, including AML, MDS, NHL, and renal cancer [see Warnings and Precautions (5.7)].

Musculoskeletal Disorder: myositis.

What's New

No Current Announcements.

Contact Pfizer Medical

Search

Please enter your search term(s) for DOCETAXEL, 20 MG/1 ML VIAL, U.S. PHYSICIAN PRESCRIBING INFORMATION