Does Taxotere (docetaxel) cause side effects?

Taxotere (docetaxel) is an antineoplastic (anticancer) drug used primarily for treating breast cancer. Taxotere is also a second-line treatment for patients with

Taxotere works by attacking cancer cells. Every cell in the body contains a supporting structure (almost like a skeleton) called the microtubular network. If this "skeleton" is changed or damaged, the cell can't grow or reproduce. Taxotere makes the "skeleton" in cancer cells unnaturally stiff, so that these cells can no longer grow.

Common side effects of Taxotere include

Serious side effects of Taxotere include

Drug interactions of Taxotere include drugs that reduce the activity of liver enzymes that break down Taxotere and other drugs increase the blood levels of Taxotere and increase its side effects such as ketoconazole, erythromycin, and protease inhibitors

Taxotere can cause fetal harm when administered to pregnant women. Women of childbearing potential should use an adequate form of contraception and should be advised not to become pregnant during therapy with Taxotere. 

It is unknown if Taxotere is excreted in breast milk. Because of the risk for serious adverse reactions in nursing infants, mothers should discontinue breastfeeding prior to taking Taxotere.

What are the important side effects of Taxotere (docetaxel)?

Following are some of the common side effects associated with docetaxel. Patients who have these or other side effects should tell their doctor or nurse.

The most common side effects of docetaxel include:

  • changes in your sense of taste
  • feeling short of breath
  • constipation
  • decreased appetite
  • changes in your fingernails or toenails
  • swelling of your hands, face, or feet
  • feeling weak or tired
  • joint and muscle pain
  • nausea and vomiting
  • diarrhea
  • mouth or lips sores
  • hair loss
  • rash
  • redness of the eye, excess tearing
  • skin reactions at the site of docetaxel administration such as increased skin pigmentation, redness, tenderness, swelling, warmth or dryness of the skin
  • tissue damage if docetaxel leaks out of the vein into the tissues

Tell your doctor if you have any side effect that bothers you or does not go away. These are not all the possible side effects of docetaxel. For more information talk to your doctor or pharmacist.

Taxotere (docetaxel) side effects list for healthcare professionals

The most serious adverse reactions from Taxotere are:

  • Toxic Deaths
  • Hepatic Impairment
  • Hematologic Effects
  • Enterocolitis and Neutropenic Colitis
  • Hypersensitivity Reactions
  • Fluid Retention
  • Acute Myeloid Leukemia
  • Cutaneous Reactions
  • Neurologic Reactions
  • Eye Disorders
  • Asthenia
  • Alcohol Content

The most common adverse reactions across all Taxotere indications are

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.

Clinical Trials 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 other tumor types. (See Table 3)

Table 3: Summary of Adverse Reactions in Patients Receiving Taxotere at 100 mg/m2

Adverse ReactionAll Tumor Types Normal LFTs*
n=2045
%
All Tumor Types Elevated LFTs**
n=61
%
Breast Cancer Normal LFTs*
n=965
%
Hematologic
Neutropenia
  <2000 cells/mm3969699
  <500 cells/mm3758886
Leukopenia
  <4000 cells/mm3969899
  <1000 cells/mm3324744
Thrombocytopenia
  <100,000 cells/mm38259
Anemia
  <11 g/dL909294
  <8 g/dL9318
Febrile Neutropenia***112612
Septic Death251
Non-Septic Death171
Infections
  Any223322
  Severe6166
Fever in Absence of Infection
  Any314135
  Severe282
Hypersensitivity Reactions
Regardless of Premedication
  Any212018
  Severe4103
With 3-day Premedicationn=92n=3n=92
  Any153315
  Severe202
Fluid Retention
Regardless of Premedication
  Any473960
  Severe789
With 3-day Premedicationn=92n=3n=92
  Any646764
  Severe7337
Neurosensory
  Any493458
  Severe406
Cutaneous
  Any485447
  Severe5105
Nail Changes
  Any312341
  Severe354
Gastrointestinal
Nausea393842
Vomiting222323
Diarrhea393343
  Severe556
Stomatitis
  Any424952
  Severe6137
Alopecia766274
Asthenia
  Any625366
  Severe132515
Myalgia
  Any191621
  Severe222
Arthralgia978
Infusion Site Reactions434
*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 Reactions
  • 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 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. 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 Taxotere.
Cutaneous Reactions
  • Severe skin toxicity is discussed elsewhere in the label. 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 Reactions
  • Neurologic reactions are discussed elsewhere in the label.
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
  • Seven of 86 (8.1%) 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 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 Taxotere, 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 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 AST and/or ALT >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 4 and 5).

Table 4: 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

Adverse ReactionTaxotere
100 mg/m2
Taxotere
60 mg/m2
Normal LFTs*
n=730
%
Elevated LFTs**
n=18
%
Normal LFTs*
n=174
%
Neutropenia
  Any   <2000 cells/mm39810095
  Grade 4   <500 cells/mm3849475

Thrombocytopenia

  Any   <100,000 cells/mm3114414
  Grade 4   <20,000 cells/mm31171
Anemia   <11 g/dL959465
Infection***
  Any23391
  Grade 3 and 47330
Febrile Neutropenia****
  By Patient12330
  By Course290
Septic Death261
Non-Septic Death1110
*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

Table 5: 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

Adverse ReactionTaxotere 100 mg/m2Taxotere 60 mg/m2
Normal LFTs*
n=730
%
Elevated LFTs**
n=18
%
Normal LFTs*
n=174
%
Acute Hypersensitivity
  Reaction Regardless of Premedication
    Any1361
    Severe100
Fluid Retention***
  Regardless of Premedication
    Any566113
    Severe8170
Neurosensory
    Any575020
    Severe600
    Myalgia23333
Cutaneous
    Any456131
    Severe5170
Asthenia
    Any654466
    Severe17220
Diarrhea
    Any4228NA
    Severe611
Stomatitis
    Any536719
    Severe8391
*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
NA = not available

  • In the three-arm monotherapy trial, TAX313, which compared Taxotere 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 Taxotere 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 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 Taxotere in the Adjuvant Treatment Of Breast Cancer
  • The following table presents treatment emergent adverse reactions observed in 744 patients, who were treated with Taxotere 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 Taxotere in Combination with Doxorubicin and Cyclophosphamide (TAX316).

Adverse ReactionTaxotere 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
%
AnyGrade 3/4AnyGrade 3/4
Anemia924722
Neutropenia71668249
Fever in absence of infection471170
Infection394362
Thrombocytopenia392281
Febrile neutropenia25N/A3N/A
Neutropenic infection12N/A6N/A
Hypersensitivity reactions13140
Lymphedema4010
Fluid Retention*351150
Peripheral edema27070
Weight gain13090
Neuropathy sensory260100
Neuro-cortical5161
Neuropathy motor4020
Neuro-cerebellar2020
Syncope2110
Alopecia98N/A97N/A
Skin toxicity271180
Nail disorders190140
Nausea8158810
Stomatitis697532
Vomiting454597
Diarrhea354282
Constipation341321
Taste perversion281150
Anorexia222181
Abdominal Pain11150
Amenorrhea62N/A52N/A
Cough140100
Cardiac dysrhythmias8060
Vasodilatation271211
Hypotension2010
Phlebitis1010
Asthenia8111716
Myalgia271100
Arthralgia19190
Lacrimation disorder11070
Conjunctivitis5070
* COSTART term and grading system for events related to treatment.

  • 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
  • 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 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 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 Taxotere as Monotherapy for Non-Small Cell Lung Cancer Previously Treated with Platinum-Based Chemotherapy*

Adverse ReactionTaxotere 75 mg/m2
n=176
%
Best Supportive
Care
n=49
%
Vinorelbine/ Ifosfamide
n=119
%
Neutropenia
  Any841483
  Grade 3/4651257
Leukopenia
  Any84689
  Grade 3/449043
Thrombocytopenia
  Any808
  Grade 3/4302
Anemia
  Any915591
  Grade 3/491214
Febrile Neutropenia**6NA1
Infection
  Any342930
  Grade 3/41069
Treatment Related Mortality3NA3
Hypersensitivity Reactions
  Any601
  Grade 3/4300
Fluid Retention
  Any34ND23
  Severe33
Neurosensory
  Any231429
  Grade 3/4265
Neuromotor
  Any16810
  Grade 3/4563
Skin
  Any20617
  Grade 3/4121
Gastrointestinal
Nausea
  Any343131
  Grade 3/4548
Vomiting
  Any222722
  Grade 3/4326
Diarrhea
  Any23612
  Grade 3/4304
Alopecia563550
Asthenia
  Any535754
  Severe***183923
Stomatitis
  Any2668
  Grade 3/4201
Pulmonary
  Any414945
  Grade 3/4212919
Nail Disorder
  Any1102
  Severe***100
Myalgia
  Any603
  Severe***000
Arthralgia
  Any322
  Severe***001
Taste Perversion
  Any600
  Severe***100
*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
***COSTART term and grading system
Not Applicable
Not Done

Combination Therapy With Taxotere In Chemotherapy-Naive 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-Naive Advanced Non-Small Cell Lung Cancer Patients Receiving Taxotere in Combination with Cisplatin

Adverse ReactionTaxotere 75 mg/m2 + Cisplatin
75 mg/m2
n=406
%
Vinorelbine 25 mg/m2 + Cisplatin 100 mg/m2
n=396
%
Neutropenia
  Any9190
  Grade 3/47478
Febrile Neutropenia55
Thrombocytopenia
  Any1515
  Grade 3/434
Anemia
  Any8994
  Grade 3/4725
Infection
  Any3537
  Grade 3/488
Fever in absence of infection
  Any3329
  Grade 3/4< 11
Hypersensitivity Reaction*
  Any124
  Grade 3/43< 1
Fluid Retention**
  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 3/444
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
* Replaces NCI term “Allergy”
** 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) demonstrated a higher incidence of
    • thrombocytopenia,
    • diarrhea,
    • fluid retention,
    • hypersensitivity reactions,
    • skin toxicity,
    • alopecia and
    • nail changes on the Taxotere+carboplatin arm.
  • A higher incidence of the following was observed on the vinorelbine+cisplatin arm
    •  anemia,
    • neurosensory toxicity,
    • nausea,
    • vomiting,
    • anorexia and
    • asthenia.

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 9).

Table 9: Clinically Important Treatment Emergent Adverse Reactions (Regardless of Relationship) in Patients with Prostate Cancer who Received Taxotere in Combination with Prednisone (TAX327)

Adverse ReactionTaxotere 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
%
AnyGrade 3/4AnyGrade 3/4
Anemia675582
Neutropenia41324822
Thrombocytopenia3181
Febrile neutropenia3N/A2N/A
Infection326204
Epistaxis6020
Allergic Reactions8110
Fluid Retention*24150
Weight Gain*8030
Peripheral Edema*18020
Neuropathy Sensory30270
Neuropathy Motor7231
Rash/Desquamation6031
Alopecia65N/A13N/A
Nail Changes30080
Nausea413362
Diarrhea322101
Stomatitis/Pharyngitis20180
Taste Disturbance18070
Vomiting172142
Anorexia171140
Cough12080
Dyspnea15391
Cardiac left ventricular function100221
Fatigue535355
Myalgia150131
Tearing10120
Arthralgia8151
*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 10).

Table 10: Clinically Important Treatment Emergent Adverse Reactions Regardless of Relationship to Treatment in the Gastric Cancer Study

Adverse ReactionTaxotere 75 mg/m2 + cisplatin 75 mg/m2 + fluorouracil 750 mg/m2
n=221
Cisplatin 100 mg/m2 + fluorouracil 1000 mg/m2
n=224
Any
%
Grade 3/4
%
Any
%
Grade 3/4
%
Anemia97189326
Neutropenia96828357
Fever in the absence of infection362231
Thrombocytopenia2683914
Infection29162310
Febrile neutropenia16N/A5N/A
Neutropenic infection16N/A10N/A
Allergic reactions10260
Fluid retention*15040
Edema*13030
Lethargy63215818
Neurosensory388253
Neuromotor9383
Dizziness16582
Alopecia675411
Rash/itch12190
Nail changes8000
Skin desquamation2000
Nausea73167619
Vomiting67157319
Anorexia51135412
Stomatitis59216127
Diarrhea7820508
Constipation252343`
Esophagitis/dysphagia/odyn ophagia162145
Gastrointestinal pain/cramping11273
Cardiac dysrhythmias5221
Myocardial ischemia1032
Tearing8020
Altered hearing60132
Clinically important treatment emergent adverse reactions were determined based upon frequency, severity, and clinical impact of the adverse reaction.
*Related to treatment

Head And Neck Cancer

Combination Therapy with Taxotere in Head and Neck Cancer

Table 11 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 11: 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)

Adverse Reaction
(by Body System)
TAX323
(n=355)
TAX324
(n=494)
Taxotere
arm (n=174)
Comparator
arm (n=181)
Taxotere
arm (n=251)
Comparator
arm (n=243)
Any
%
Grade 3/4
%
Any
%
Grade 3/4
%
Any
%
Grade 3/4
%
Any
%
Grade 3/4
%
Neutropenia9376875395848456
Anemia899881490128610
Thrombocytopenia24547182843111
Infection279268236285
Febrile neutropenia* 5N/A2N/A12N/A7N/A
Neutropenic infection14N/A8N/A12N/A8N/A
Cancer pain2151631792011
Lethargy4133836155610
Fever in the absence of infection321370304283
Myalgia101707072
Weight loss211271142142
Allergy60302000
Fluid retention**20014113172
Edema only1307012161
Weight gain only60600010
Dizziness2051164152
Neurosensory181111141140
Altered hearing60103131193
Neuromotor214190102
Alopecia8111430684441
Rash/itch12060200161
Dry skin60205030
Desquamation41602050
Nausea47151777148014
Stomatitis434471166216827
Vomiting2613955686310
Diarrhea333244487403
Constipation171161271381
Anorexia16125340123412
Esophagitis/dysphagia/ Odynophagia13118325132610
Taste, sense of smell altered10050200171
Gastrointestinal pain/cramping8191155102
Heartburn6060132131
Gastrointestinal bleeding42005121
Cardiac dysrhythmia22216353
Venous***32624254
Ischemia myocardial22102111
Tearing20102020
Conjunctivitis1010100.40
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

Postmarketing Experience

The following adverse reactions have been identified from clinical trials and/or postmarketing 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, 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 has been reported in patients treated with docetaxel in combination regimens including doxorubicin, 5-fluorouracil and/or cyclophosphamide, and may be associated with fatal outcome.
  • Cutaneous: very rare cases of cutaneous lupus erythematosus and rare cases of bullous eruptions such as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and Scleroderma-like changes usually preceded by peripheral lymphedema. In some cases multiple factors may have contributed to the development of these effects. Severe hand and foot syndrome has been reported. Cases of permanent alopecia have been reported.
  • Gastrointestinal: enterocolitis, including colitis, ischemic colitis, and neutropenic enterocolitis, has been reported with a potential fatal outcome. Abdominal pain, anorexia, constipation, duodenal ulcer, esophagitis, gastrointestinal hemorrhage, gastrointestinal perforation, intestinal obstruction, ileus, 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. 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. Hypersensitivity reactions with potential fatal outcome have been reported with docetaxel in patients who previously experienced hypersensitivity reactions to paclitaxel.
  • 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. Cases of cystoid macular edema (CME) have been reported in patients treated with Taxotere.
  • 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/pneumonitis, interstitial lung disease, interstitial pneumonia, respiratory failure, and pulmonary fibrosis have rarely been reported and may be associated with fatal outcome. Rare cases of radiation pneumonitis have been reported in patients receiving concomitant radiotherapy.
  • Renal: renal insufficiency and renal failure have been reported, the majority of these cases were associated with concomitant nephrotoxic drugs.
  • Metabolism and nutrition disorders: electrolyte imbalance, including cases of hyponatremia, hypokalemia, hypomagnesemia, and hypocalcemia has been reported.

What drugs interact with Taxotere (docetaxel)?

  • Docetaxel is a CYP3A4 substrate. In vitro studies have shown that the metabolism of docetaxel may be modified by the concomitant administration of compounds that induce, inhibit, or are metabolized by cytochrome P450 3A4.
  • In vivo studies showed that the exposure of docetaxel increased 2.2-fold when it was coadministered with ketoconazole, a potent inhibitor of CYP3A4.
  • Protease inhibitors, particularly ritonavir, may increase the exposure of docetaxel. Concomitant use of Taxotere and drugs that inhibit CYP3A4 may increase exposure to docetaxel and should be avoided.
  • In patients receiving treatment with Taxotere, close monitoring for toxicity and a Taxotere dose reduction could be considered if systemic administration of a potent CYP3A4 inhibitor cannot be avoided.

Summary

Taxotere (docetaxel) is an antineoplastic (anticancer) drug used primarily for treating breast cancer. Taxotere is also a second-line treatment for patients with non-small cell lung cancer, prostate cancer, gastric adenocarcinoma, and squamous cell carcinoma of the head and neck. Common side effects of Taxotere include changes in sense of taste, shortness of breath, constipation, decreased appetite, changes in fingernails or toenails, swelling of hands/face/feet, weakness, tiredness, joint and muscle pain, nausea, vomiting, diarrhea, mouth or lip sores, hair loss, rash, eye redness, excess tearing, skin reactions at the administration site (such as increased skin pigmentation, redness, tenderness, swelling, warmth or dryness of the skin), and tissue damage if Taxotere leaks out of the vein into the tissues. Taxotere can cause fetal harm when administered to pregnant women. Because of the risk for serious adverse reactions in nursing infants, mothers should discontinue breastfeeding prior to taking Taxotere.

Treatment & Diagnosis

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Medically Reviewed on 12/9/2020
References
FDA Prescribing Information

Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.