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Taxotere (Docetaxel) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

Adverse reactions are described for TAXOTERE according to indication.

Clinical Trial Experience

  • Breast Cancer

Monotherapy with TAXOTERE for locally advanced or metastatic breast cancer after failure of prior chemotherapy

TAXOTERE 100 mg/m2: Adverse drug reactions occurring in at least 5% of patients are compared for three populations who received TAXOTERE 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 TAXOTERE. At least 95% of these patients did not receive hematopoietic support. The safety profile is generally similar in patients receiving TAXOTERE for the treatment of breast cancer and in patients with othertumor types (See Table 4).

Table 4 - Summary of Adverse Reactions in Patients Receiving TAXOTERE at 100 mg/m2
Adverse ReactionAll Tumor Types
Normal LFTs 1
n=2045
%
All Tumor Types
Elevated LFTs 2
n=61
%
Breast Cancer
Normal LFTs
n=965
%
Hematologic
Neutropenia
  <2000 cells/mm3 95.596.498.5
  <500 cells/mm3 75.487.585.9
Leukopenia
  <4000 cells/mm3 95.698.398.6
  <1000 cells/mm3 31.646.643.7
Thrombocytopenia
  <100,000 cells/mm3 8.024.69.2
Anemia
  <11 g/dL90.491.893.6
  <8 g/dL8.831.17.7
Febrile Neutropenia 3 11.026.212.3
Septic Death 1.64.91.4
Non-Septic Death 0.66.60.6
Infections
  Any21.632.822.2
  Severe6.116.46.4
Fever in Absence of Infection
  Any31.241.035.1
  Severe2.18.22.2
Hypersensitivity Reactions
Regardless of Premedication
  Any21.019.717.6
  Severe4.29.82.6
With 3-day Premedicationn=92n=3n=92
  Any15.233.315.2
  Severe2.202.2
Fluid Retention
Regardless of Premedication
  Any47.039.359.7
  Severe6.98.28.9
With 3-day Premedicationn=92n=3n=92
  Any64.166.764.1
  Severe6.533.36.5
Neurosensory
  Any49.334.458.3
  Severe4.305.5
Cutaneous
  Any47.654.147.0
  Severe4.89.85.2
Nail Changes
  Any30.623.040.5
  Severe2.54.93.7
Gastrointestinal
Nausea38.837.742.1
Vomiting22.323.023.4
Diarrhea38.732.842.6
  Severe4.74.95.5
Stomatitis
  Any41.749.251.7
  Severe5.513.07.4
Alopecia 75.862.374.2
Asthenia
  Any61.852.566.3
  Severe12.824.614.9
Myalgia
  Any18.916.421.1
  Severe1.51.61.8
Arthralgia 9.26.68.2
Infusion Site Reactions 4.43.34.0

1 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
2 Elevated Baseline LFTs: SGOT and/or SGPT >1.5 times ULN concurrent with alkaline phosphatase >2.5 times ULN
3 Febrile Neutropenia: ANC grade 4 with fever >38°C with IV antibiotics and/or hospitalization


Hematologic [see Warnings and Precautions].

Reversible marrow suppression was the major dose-limiting toxicity of TAXOTERE. 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 IV 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 are discussed in the Boxed Warning, Warnings and Precautions sections. 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 appropriate therapy.

Fluid Retention [see Boxed Warning, Warnings and Precautions, Premedication Regimen].

Cutaneous

Severe skin toxicity is discussed in Warnings and Precautions . 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 TAXOTERE 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 [see Warnings and Precautions (5.11 )].

Gastrointestinal

Gastrointestinal reactions (nausea and/or vomiting and/or 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

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 occurred rarely. 8.1% (7/86) of metastatic breast cancer patients receiving TAXOTERE 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

In patients with normal LFTs at baseline, bilirubin values greater than the ULN occurred in 8.9% of patients. Increases in SGOT or SGPT >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 TAXOTERE, increases in SGOT and/or SGPT >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 TAXOTERE 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 SGOT and/or SGPT >1.5 times ULN concurrent with alkaline phosphatase >2.5 times ULN); and 174 patients in Japanese studies given TAXOTERE at 60 mg/m2 who had normal LFTs (see Tables 5 and 6).

Table 5 - Hematologic Adverse Reactions in Breast Cancer Patients Previously Treated with Chemotherapy Treated at TAXOTERE 100 mg/m2 with Normal or Elevated Liver Function Tests or 60 mg/m2 with Normal Liver Function Tests
TAXOTERE
100 mg/m2
TAXOTERE
60 mg/m2
Adverse ReactionNormal LFTs 1
n=730
%
Elevated LFTs 2
n=18
%
Normal LFTs
n=174
%
Neutropenia
  Any        <2000 cells/mm3 98.410095.4
  Grade 4   <500 cells/mm3 84.493.874.9
Thrombocytopenia
  Any        <100,000 cells/mm3 10.844.414.4
  Grade 4  <20,000 cells/mm3 0.616.71.1
Anemia    <11 g/dL94.694.464.9
Infection 3
  Any22.538.91.1
  Grade 3 and 47.133.30
Febrile Neutropenia 4
  By Patient11.833.30
  By Course2.48.60
Septic Death 1.55.61.1
Non-Septic Death 1.111.10

1 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
2 Elevated Baseline LFTs: SGOT and/or SGPT >1.5 times ULN concurrent with alkaline phosphatase >2.5 times ULN
3 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.
4 Febrile Neutropenia: For 100 mg/m2, ANC grade 4 and fever >38°C with IV antibiotics and/or hospitalization; for 60 mg/m2, ANC grade 3/4 and fever >38.1°C


Table 6 - Non-Hematologic Adverse Reactions in Breast Cancer Patients Previously Treated with Chemotherapy Treated at TAXOTERE 100 mg/m2 with Normal or Elevated Liver Function Tests or 60 mg/m2 with Normal Liver Function Tests
TAXOTERE
100 mg/m2
TAXOTERE
60 mg/m2
Adverse ReactionNormal LFTs 1
n=730
%
Elevated LFTsElevated Baseline Liver Function: SGOT and/or SGPT >1.5 times ULN concurrent with alkaline phosphatase >2.5 times ULN
n=18
%
Normal LFTs
n=174
%
Acute Hypersensitivity
  Reaction Regardless of Premedication
    Any13.05.60.6
    Severe1.200
Fluid Retention 2
  Regardless of Premedication
    Any56.261.112.6
    Severe7.916.70
Neurosensory
    Any56.85019.5
    Severe5.800
Myalgia 22.733.33.4
Cutaneous
    Any44.861.130.5
    Severe4.816.70
Asthenia
    Any65.244.465.5
    Severe16.622.20
Diarrhea
    Any42.227.8NA
    Severe6.311.1
Stomatitis
    Any53.366.719.0
    Severe7.838.90.6
1 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
2 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
NA = not available

In the three-arm monotherapy trial, TAX313, which compared TAXOTERE 60, 75 and 100 mg/m2 in advanced breast cancer, the overall safety profile was consistent with the safety profile observed in previous TAXOTERE trials. Grade 3/4 or severe adverse reactions occurred in 49.0% of patients treated with TAXOTERE 60 mg/m2 compared to 55.3% and 65.9% treated with 75 and 100 mg/m2 respectively. Discontinuation due to adverse reactions was reported in 5.3% of patients treated with 60 mg/m2 vs. 6.9% and 16.5% for patients treated at 75 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 and 100 mg/m2 respectively.

The following adverse reactions were associated with increasing docetaxel doses: fluid retention (26%, 38%, and 46% at 60, 75, 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 TAXOTERE in the adjuvant treatment of breast cancer

The following table presents treatment emergent adverse reactions (TEAEs) observed in 744 patients, who were treated with TAXOTERE 75 mg/m2 every 3 weeks in combination with doxorubicin and cyclophosphamide (see Table 7).

Table 7 - Clinically Important Treatment Emergent Adverse Reactions Regardless of Causal Relationship in Patients Receiving TAXOTERE in Combination with Doxorubicin and Cyclophosphamide (TAX316).
TAXOTERE 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 G 3/4 Any G 3/4
Anemia 91.54.371.71.6
Neutropenia 71.465.582.049.3
Fever in absence of infection 46.51.317.10.0
Infection 39.43.936.32.2
Thrombocytopenia 39.42.027.71.2
Febrile neutropenia 24.7N/A2.5N/A
Neutropenic infection 12.1N/A6.3N/A
Hypersensitivity reactions 13.41.33.70.1
Lymphedema 4.40.01.20.0
Fluid Retention 1 35.10.914.70.1
Peripheral edema26.90.47.30.0
Weight gain12.90.38.60.3
Neuropathy sensory 25.50.010.20.0
Neuro-cortical 5.10.56.40.7
Neuropathy motor 3.80.12.20.0
Neuro-cerebellar 2.40.12.00.0
Syncope 1.60.51.20.3
Alopecia 97.8N/A97.1N/A
Skin toxicity 26.50.817.70.4
Nail disorders 18.50.414.40.1
Nausea 80.55.188.09.5
Stomatitis 69.47.152.92.0
Vomiting 44.54.359.27.3
Diarrhea 35.23.827.91.8
Constipation 33.91.131.81.4
Taste perversion 27.80.715.10.0
Anorexia 21.62.217.71.2
Abdominal Pain 10.90.75.30.0
Amenorrhea 61.7N/A52.4N/A
Cough 13.70.09.80.1
Cardiac dysrhythmias 7.90.36.00.3
Vasodilatation 27.01.121.20.5
Hypotension 2.60.01.10.1
Phlebitis 1.20.00.80.0
Asthenia 80.811.271.25.6
Myalgia 26.70.89.90.0
Arthralgia 19.40.59.00.3
Lacrimation disorder 11.30.17.10.0
Conjunctivitis 5.10.36.90.1

1 COSTART term and grading system for events related to treatment.


Of the 744 patients treated with TAC, 36.3% experienced severe TEAEs 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

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.

Gastrointestinal events

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

Cardiovascular events

More cardiovascular events were reported in the TAC arm vs. the FAC arm; dysrhythmias, all grades (7.9% vs. 6.0%), hypotension, all grades (2.6% vs. 1.1%) and CHF (2.3% vs. 0.9%, at 70 months median follow-up). One patient in each arm died due to heart failure.

Acute Myeloid Leukemia (AML)

Treatment-related acute myeloid leukemia or myelodysplasia is known to occur in patients treated with anthracyclines and/or cyclophosphamide, including use in adjuvant therapy for breast cancer. AML occurs at a higher frequency when these agents are given in combination with radiation therapy. AML occurred in the adjuvant breast cancer trial (TAX316). The cumulative risk of developing treatment-related AML at 5 years in TAX316 was 0.4% for TAC-treated patients and 0.1% for FAC-treated patients. This risk of AML is comparable to the risk observed for other anthracyclines/cyclophosphamide containing adjuvant breast chemotherapy regimens.

  • Lung Cancer

Monotherapy with TAXOTERE for unresectable, locally advanced or metastatic NSCLC previously treated with platinum-based chemotherapy

TAXOTERE 75 mg/m2: Treatment emergent adverse drug reactions are shown in Table 8. 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 8 - Treatment Emergent Adverse Reactions Regardless of Relationship to Treatment in Patients Receiving TAXOTERE as Monotherapy for Non-Small Cell Lung Cancer Previously Treated with Platinum-Based ChemotherapyNormal 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
Adverse ReactionTAXOTERE
75 mg/m2
n=176
%
Best Supportive Care
n=49
%
Vinorelbine/Ifosfamide
n=119
%
Neutropenia
  Any84.114.383.2
  Grade 3/465.312.257.1
Leukopenia
  Any83.56.189.1
  Grade 3/449.4042.9
Thrombocytopenia
  Any8.007.6
  Grade 3/42.801.7
Anemia
  Any91.055.190.8
  Grade 3/49.112.214.3
Febrile Neutropenia Febrile Neutropenia: ANC grade 4 with fever >38°C with IV antibiotics and/or hospitalization 6.3NA 1 0.8
Infection
  Any33.528.630.3
  Grade 3/410.26.19.2
Treatment Related Mortality 2.8NA 3.4
Hypersensitivity Reactions
  Any5.700.8
  Grade 3/42.800
Fluid Retention
  Any33.5NDNot Done 22.7
  Severe2.83.4
Neurosensory
  Any23.314.328.6
  Grade 3/41.76.15.0
Neuromotor
  Any15.98.210.1
  Grade 3/44.56.13.4
Skin
  Any19.96.116.8
  Grade 3/40.62.00.8
Gastrointestinal
  Nausea
    Any33.530.631.1
    Grade 3/45.14.17.6
  Vomiting
    Any21.626.521.8
    Grade 3/42.82.05.9
  Diarrhea
    Any22.76.111.8
    Grade 3/42.804.2
Alopecia 56.334.749.6
Asthenia
  Any52.857.153.8
  Severe 2 18.238.822.7
Stomatitis
  Any26.16.17.6
  Grade 3/41.700.8
Pulmonary
  Any40.949.045.4
  Grade 3/421.028.618.5
Nail Disorder
  Any11.401.7
  Severe 1.100
Myalgia
  Any6.302.5
  Severe 000
Arthralgia
  Any3.42.01.7
  Severe 000.8
Taste Perversion
  Any5.700
  Severe 0.600

1 Not Applicable;
2 COSTART term and grading system


Combination therapy with TAXOTERE in chemotherapy-naïve advanced unresectable or metastatic NSCLC

Table 9 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 9 - Adverse Reactions Regardless of Relationship to Treatment in Chemotherapy-Naïve Advanced Non-Small Cell Lung Cancer Patients Receiving TAXOTERE in Combination with Cisplatin
Adverse Reaction

TAXOTERE 75 mg/m2 + Cisplatin
75 mg/m2
n=406
%
Vinorelbine 25 mg/m2 + Cisplatin 100 mg/m2
n=396
%
Neutropenia
  Any91 90
  Grade 3/47478
Febrile Neutropenia 55
Thrombocytopenia
  Any15 15
  Grade 3/434
Anemia
  Any89 94
  Grade 3/4725
Infection
  Any3537
  Grade 3/488
Fever in absence of infection
  Any3329
  Grade 3/4< 1 1
Hypersensitivity ReactionReplaces NCI term "Allergy"
  Any124
  Grade 3/43< 1
Fluid Retention 1
  Any5442
  All severe or life-threatening events22
Pleural effusion
  Any2322
  All severe or life-threatening events22
Peripheral edema
  Any3418
  All severe or life-threatening events<1<1
Weight gain
  Any159
  All severe or life-threatening events<1<1
Neurosensory
  Any4742
  Grade 3/44 4
Neuromotor
  Any1917
  Grade 3/436
Skin
  Any1614
  Grade 3/4<11
Nausea
  Any7276
  Grade 3/41017
Vomiting
  Any5561
  Grade 3/4816
Diarrhea
  Any4725
  Grade 3/473
Anorexia
  Any4240
  All severe or life-threatening events55
Stomatitis
  Any2421
  Grade 3/421
Alopecia
  Any7542
  Grade 3<10
Asthenia
  Any7475
  All severe or life-threatening events1214
Nail Disorder
  Any14<1
  All severe events<10
Myalgia
  Any1812
  All severe events<1<1

1 COSTART term and grading system


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 TAXOTERE+carboplatin (which did not demonstrate a superior survival associated with TAXOTERE, [see Clinical Studies]) demonstrated a higher incidence of thrombocytopenia, diarrhea, fluid retention, hypersensitivity reactions, skin toxicity, alopecia and nail changes on the TAXOTERE+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 TAXOTERE in patients with prostate cancer

The following data are based on the experience of 332 patients, who were treated with TAXOTERE 75 mg/m2 every 3 weeks in combination with prednisone 5 mg orally twice daily (see Table 10).

Table 10 - Clinically Important Treatment Emergent Adverse Reactions (Regardless of Relationship) in Patients with Prostate Cancer who Received TAXOTERE in Combination with Prednisone (TAX327)
TAXOTERE 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 ReactionAnyG 3/4AnyG 3/4
Anemia 66.54.957.81.8
Neutropenia 40.932.048.221.7
Thrombocytopenia 3.40.67.81.2
Febrile neutropenia 2.7N/A1.8N/A
Infection 32.25.720.34.2
Epistaxis 5.70.31.80.0
Allergic Reactions 8.40.60.60.0
Fluid Retention 1 24.40.64.50.3
Weight Gain 7.50.33.00.0
Peripheral Edema 18.10.31.50.0
Neuropathy Sensory 30.41.87.20.3
Neuropathy Motor 7.21.53.00.9
Rash/Desquamation 6.00.33.30.6
Alopecia 65.1N/A12.8N/A
Nail Changes 29.50.07.50.0
Nausea 41.02.735.51.5
Diarrhea 31.62.19.61.2
Stomatitis/Pharyngitis 19.60.98.40.0
Taste Disturbance 18.40.06.60.0
Vomiting 16.91.514.01.5
Anorexia 16.61.214.30.3
Cough 12.30.07.80.0
Dyspnea 15.12.78.70.9
Cardiac left ventricular function 9.60.322.11.2
Fatigue 53.34.534.65.1
Myalgia 14.50.312.80.9
Tearing 9.90.61.50.0
Arthralgia 8.10.65.11.2

1 Related to treatment


  • Gastric Cancer

Combination therapy with TAXOTERE 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 TAXOTERE 75 mg/m2 in combination with cisplatin and fluorouracil (see Table 11).

Table 11 - Clinically Important Treatment Emergent Adverse Reactions Regardless of Relationship to Treatment in the Gastric Cancer Study
TAXOTERE 75 mg/m2 +
cisplatin 75 mg/m2 +
fluorouracil 750 mg/m2
n=221
Cisplatin 100 mg/m2 +
fluorouracil 1000 mg/m2
n=224
Adverse ReactionAny
%
G3/4
%
Any
%
G3/4
%
Clinically important TEAEs were determined based upon frequency, severity, and clinical impact of the adverse reaction.
Anemia 96.818.293.325.6
Neutropenia 95.582.383.356.8
Fever in the absence of infection 35.71.822.81.3
Thrombocytopenia 25.57.739.013.5
Infection 29.416.322.810.3
Febrile neutropenia 16.4N/A4.5N/A
Neutropenic infection 15.9N/A10.4N/A
Allergic reactions 10.41.85.80
Fluid retention 1 14.904.00.4
Edema 13.103.10.4
Lethargy 62.921.358.017.9
Neurosensory 38.07.724.63.1
Neuromotor 8.63.27.62.7
Dizziness 15.84.58.01.8
Alopecia 66.55.041.11.3
Rash/itch 11.80.98.50.0
Nail changes 8.10.00.00.0
Skin desquamation 1.80.00.40.0
Nausea 73.315.876.318.8
Vomiting 66.514.973.218.8
Anorexia 50.713.154.011.6
Stomatitis 59.320.861.227.2
Diarrhea 77.820.449.68.0
Constipation 25.31.833.93.1
Esophagitis/dysphagia/odynophagia 16.31.813.84.9
Gastrointestinal pain/cramping 11.31.87.12.7
Cardiac dysrhythmias 4.52.32.20.9
Myocardial ischemia 0.90.02.72.2
Tearing 8.102.20.4
Altered hearing 6.3012.51.8

1 Related to treatment


  • Head and Neck Cancer

Combination therapy with TAXOTERE in head and neck cancer

Table 12 summarizes the safety data obtained from patients that received induction chemotherapy with TAXOTERE 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 12 – Clinically Important Treatment Emergent Adverse Reactions (Regardless of Relationship) in Patients with SCCHN Receiving Induction Chemotherapy with TAXOTERE in Combination with cisplatin and fluorouracil followed by radiotherapy (TAX323) or chemoradiotherapy (TAX324)
TAX323
(n=355)
TAX324
(n=494)
TAXOTERE arm (n=174)Comparator arm (n=181)TAXOTERE arm (n=251)Comparator arm (n=243)
Adverse Reaction
(by Body System)
Any
%
G3/4
%
Any
%
G3/4
%
Any
%
G3/4
%
Any
%
G3/4
%
Clinically important treatment emergent adverse reactions based upon frequency, severity, and clinical impact.
Neutropenia 93.176.386.752.894.883.584.256.0
Anemia 89.19.287.813.890.012.486.09.5
Thrombocytopenia 23.65.247.018.227.54.030.910.7
Infection 27.08.626.07.723.16.427.65.3
Febrile neutropeniaFebrile neutropenia: grade ≥2 fever concomitant with grade 4 neutropenia requiring i.v. antibiotics and/or hospitalization. 5.2N/A2.2N/A12.1N/A6.6N/A
Neutropenic infection 13.9N/A8.3N/A11.7N/A8.3N/A
Cancer pain 20.74.616.03.317.18.820.211.1
Lethargy 40.83.438.13.361.44.855.610.3
Fever in the absence of infection 31.60.636.5029.53.627.63.3
Myalgia 9.81.17.206.80.47.01.6
Weight loss 20.70.626.50.614.31.614.02.1
Allergy 6.302.802.000.40
Fluid retentionRelated to treatment. 20.1014.40.613.11.27.01.6
Edema only 12.606.6012.01.25.81.2
Weight gain only 5.706.100.400.80.4
Dizziness 2.305.00.615.94.015.21.6
Neurosensory 17.80.610.50.613.91.214.40.4
Altered hearing 5.709.92.812.71.218.52.5
Neuromotor 2.31.13.90.68.80.410.31.6
Alopecia 81.010.943.1067.74.043.61.2
Rash/itch 11.506.1019.9016.00.8
Dry skin 5.701.704.80.43.30
Desquamation 4.00.65.502.404.50.4
Nausea 47.10.651.47.276.513.979.814.0
Stomatitis 42.54.047.011.065.721.167.527.2
Vomiting 26.40.638.75.056.28.462.610.3
Diarrhea 32.82.923.84.447.87.240.33.3
Constipation 16.70.616.01.127.11.237.90.8
Anorexia 16.10.624.93.340.212.434.211.5
Esophagitis/dysphagia/
Odynophagia
12.61.118.22.825.112.726.39.5
Taste, sense of smell altered 10.305.0020.30.416.90.8
Gastrointestinal pain/cramping 7.50.68.80.614.74.810.31.6
Heartburn 6.306.1012.71.612.80.8
Gastrointestinal bleeding 4.01.7005.20.42.10.4
Cardiac dysrhythmia 1.71.71.70.66.02.84.52.5
VenousIncludes superficial and deep vein thrombosis and pulmonary embolism 3.42.35.51.73.62.44.93.7
Ischemia myocardial 1.71.70.601.61.21.21.2
Tearing 1.700.601.602.10
Conjunctivitis 1.101.101.200.40

Post-marketing Experiences

The following adverse reactions have been identified from clinical trials and/or post-marketing surveillance. Because they are reported from a population of unknown size, precise estimates of frequency cannot be made.

Body as a whole: diffuse pain, chest pain, radiation recall phenomenon.

Cardiovascular: atrial fibrillation, deep vein thrombosis, ECG abnormalities, thrombophlebitis, pulmonary embolism, syncope, tachycardia, myocardial infarction.

Cutaneous: very rare cases of cutaneous lupus erythematosus and rare cases of bullous eruptions such as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis. In some cases multiple factors may have contributed to the development of these effects. Severe hand and foot syndrome has been reported.

Gastrointestinal: abdominal pain, anorexia, constipation, duodenal ulcer, esophagitis, gastrointestinal hemorrhage, gastrointestinal perforation, ischemic colitis, colitis, intestinal obstruction, ileus, neutropenic enterocolitis and dehydration as a consequence to gastrointestinal events have been reported.

Hematologic: bleeding episodes. Disseminated intravascular coagulation (DIC), often in association with sepsis or multiorgan failure, has been reported. Very care cases of acute myeloid leukemia and myelodysplasic syndrome have been reported in association with TAXOTERE when used in combination with other chemotherapy agents and/or radiotherapy.

Hypersensitivity: rare cases of anaphylactic shock have been reported. Very rarely these cases resulted in a fatal outcome in patients who received premedication.

Hepatic: rare cases of hepatitis, sometimes fatal primarily in patients with pre-existing liver disorders, have been reported.

Neurologic: confusion, rare cases of seizures or transient loss of consciousness have been observed, sometimes appearing during the infusion of the drug.

Ophthalmologic: conjunctivitis, lacrimation or lacrimation with or without conjunctivitis. Excessive tearing which may be attributable to lacrimal duct obstruction has been reported. Rare cases of transient visual disturbances (flashes, flashing lights, scotomata) typically occurring during drug infusion and in association with hypersensitivity reactions have been reported. These were reversible upon discontinuation of the infusion.

Hearing: rare cases of ototoxicity, hearing disorders and/or hearing loss have been reported, including cases associated with other ototoxic drugs.

Respiratory: dyspnea, acute pulmonary edema, acute respiratory distress syndrome, interstitial pneumonia. Pulmonary fibrosis has been rarely reported. Rare cases of radiation pneumonitis have been reported in patients receiving concomitant radiotherapy.

Renal: renal insufficiency.



REPORTS OF SUSPECTED TAXOTERE SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Taxotere. The information is not vetted and should not be considered as verified clinical evidence.

Possible Taxotere side effects / adverse reactions in 49 year old female

Reported by a physician from Germany on 2011-10-03

Patient: 49 year old female weighing 58.0 kg (127.6 pounds)

Reactions: Acute Stress Disorder, Suicidal Ideation

Adverse event resulted in: hospitalization

Suspect drug(s):
Taxotere

Other drugs received by patient: Cyclophosphamide; Epirubicin; Cyclophosphamide; Epirubicin



Possible Taxotere side effects / adverse reactions in 74 year old male

Reported by a physician from United States on 2011-10-03

Patient: 74 year old male

Reactions: Death

Adverse event resulted in: death

Suspect drug(s):
Radiotherapy
    Indication: Prostate Cancer

Casodex
    Administration route: Oral
    Indication: Prostate Cancer
    Start date: 2010-12-27

Lupron
    Indication: Prostate Cancer
    Start date: 2010-12-29

Taxotere
    Indication: Prostate Cancer

Other drugs received by patient: Lasix; Phenazopyridine HCL TAB; Mucinex; Aspirin; Albuterol Sulfate; Flonase; Lisinopril; Dakin; Coreg; Potassium Cloride; Lexapro; Multaq; Zofran; Advair Diskus 100/50; Flomax



Possible Taxotere side effects / adverse reactions in 31 year old female

Reported by a consumer/non-health professional from Ireland on 2011-10-04

Patient: 31 year old female

Reactions: Somnolence, Abdominal Pain Upper, Fatigue, Amniotic Fluid Volume Decreased, Cough, Epistaxis, Stomatitis, Vomiting, Maternal Exposure During Pregnancy, Rhinorrhoea, Paraesthesia, Haemoglobin Decreased, Insomnia, Visual Impairment, Lacrimation Increased, Premature Delivery

Adverse event resulted in: hospitalization

Suspect drug(s):
Trastuzumab
    Start date: 2011-08-15

Taxotere
    Indication: Breast Cancer Stage IV
    Start date: 2011-07-25

Trastuzumab
    Indication: Breast Cancer Stage IV
    Start date: 2011-07-25
    End date: 2011-08-15

Other drugs received by patient: ALL Other Therapeutic Products; Corticosteroid NOS



See index of all Taxotere side effect reports >>

Drug label data at the top of this Page last updated: 2008-07-11

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