Docefrez

Medical Editor: John P. Cunha, DO, FACOEP Last updated on RxList: 6/7/2022
Docefrez Side Effects Center

What Is Docefrez?

Docefrez (docetaxel) is an antineoplastic (anticancer) drug used to treat patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy. Docefrez is also used to treat locally advanced or metastatic non-small cell lung cancer after failure of prior platinum-based chemotherapy and androgen independent metastatic prostate cancer. Docefrez or docetaxel (the drug brand name is Taxotere) is a generic form of Taxotere, available in Europe.

What Are Side Effects of Docefrez?

The most common side effects Docefrez are:

Dosage for Docefrez

Docefrez (docetaxel) is available in 20 and 80 mg strength vials to be administered by intravenous drip over one hour. Doses are based on the disease process, the patient's size (in meters2), and calculated by personnel trained in the administration of potentially toxic medications. Note that most patients may need premedication with steroids before Docefrez is administered.

What Drugs, Substances, or Supplements Interact with Docefrez?

Docefrez During Pregnancy and Breastfeeding

Docefrez can cause fetal harm when administered to a pregnant woman. It is not known whether docetaxel is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from Docefrez, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Severe side effects include death due to toxicity, hepatotoxicity, neutropenia, fluid retention, bleeding, skin blistering and hypersensitivity. The safety or effectiveness of Docefrez in pediatric population is unknown. There are over 200 drugs listed that may interact with Docefrez so the treating physician needs to know all medications the patient is currently taking.

Additional Information

Our Docefrez Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

SLIDESHOW

Lung Cancer: Early Signs, Symptoms, Stages See Slideshow
Docefrez Consumer Information

You may have a life-threatening allergic reaction or a severe skin reaction. Get emergency medical help if you have signs of an allergic reaction: hives, burning eyes, skin pain, red or purple skin rash with blistering and peeling; fever, sore throat, wheezing, chest tightness, trouble breathing; feeling like you might pass out; swelling of your face, lips, tongue, or throat.

You may have swelling in your intestines, which could cause death quickly. Call your doctor right away if you have stomach pain or tenderness, diarrhea, or fever.

Some side effects may occur during the injection. Tell your caregiver if you feel light-headed, or if you have trouble breathing or fast or irregular heartbeats.

Also call your doctor at once if you have:

  • pain, burning, irritation, or skin changes where the injection was given;
  • sudden vision problems including blurred vision or loss of vision;
  • redness or swelling in your arms or legs;
  • skin rash, redness, blistering, peeling, bleeding, or small red or white bumps that contain pus;
  • numbness, burning, or tingling in your hands or feet;
  • muscle weakness in your arms, legs, feet, or hands;
  • swelling, rapid weight gain, shortness of breath;
  • signs of tumor cell breakdown--weakness, muscle cramps, nausea, vomiting, diarrhea, fast or slow heart rate, tingling around your mouth;
  • a feeling of being drunk--confusion, stumbling, extreme drowsiness;
  • liver problems--upper stomach pain, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or
  • low blood cell counts--fever, chills, tiredness, mouth sores, skin sores, easy bruising, unusual bleeding, pale skin, cold hands and feet, feeling light-headed.

Side effects may be more likely in older adults.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

Common side effects may include:

  • allergic reactions;
  • tissue damage (if docetaxel leaks into tissues);
  • swelling, warmth, tenderness, redness, dryness or darkened skin where the injection was given;
  • low blood cell counts, infections;
  • mouth or lip sores, altered sense of taste;
  • nausea, vomiting, loss of appetite;
  • constipation, diarrhea;
  • feeling short of breath;
  • eye redness, watery eyes;
  • feeling weak or tired;
  • swelling in your hands, feet, or face;
  • muscle or joint pain;
  • hair loss (may be permanent in some cases); or
  • fingernail or toenail changes.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Docefrez (docetaxel)

QUESTION

Lung cancer is a disease in which lung cells grow abnormally in an uncontrolled way. See Answer
Docefrez Professional Information

SIDE EFFECTS

The most serious adverse reactions from DOCETAXEL INJECTION are:

  • Toxic Deaths [see BOX WARNING, WARNINGS AND PRECAUTIONS]
  • Hepatic Impairment [see BOX WARNING, WARNINGS AND PRECAUTIONS]
  • Hematologic Effects [see BOX WARNING, WARNINGS AND PRECAUTIONS]
  • Enterocolitis and Neutropenic Colitis [see WARNINGS AND PRECAUTIONS]
  • Hypersensitivity Reactions [see BOX WARNING, WARNINGS AND PRECAUTIONS]
  • Fluid Retention [see BOX WARNING, WARNINGS AND PRECAUTIONS]
  • Second Primary Malignancies [see WARNINGS AND PRECAUTIONS]
  • Cutaneous Reactions [see WARNINGS AND PRECAUTIONS]
  • Neurologic Reactions [see WARNINGS AND PRECAUTIONS]
  • Eye Disorders [see WARNINGS AND PRECAUTIONS]
  • Asthenia [see WARNINGS AND PRECAUTIONS]
  • Alcohol Content [see WARNINGS AND PRECAUTIONS]

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.

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 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
<1,000 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 Premedication473960
Any789
Severen=92n=3n=92
With 3-day Premedication646764
Any7337
Severe
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 docetaxel [see WARNINGS AND PRECAUTIONS]. 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 BOX WARNING, WARNINGS AND PRECAUTIONS]. 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 INJECTION [see BOX WARNING, DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS].

Cutaneous Reactions

Severe skin toxicity is discussed elsewhere in the label [see 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 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].

Gastrointestinal Reactions

Nausea, vomiting, and diarrhea were generally mild to moderate. Severe reactions occurred in 3% to 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

Adverse ReactionDocetaxel
100 mg/m2
Docetaxel
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 Patient11330
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 Docetaxel 100 mg/m2 with Normal or Elevated Liver Function Tests or 60 mg/m2 with Normal Liver Function Tests

Adverse ReactionDocetaxel
100 mg/m2
Docetaxel
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 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 ReactionAnyGrade 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 (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 ReactionDocetaxel 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
Any18810
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 Docetaxel 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 Docetaxel in Combination with Cisplatin

Adverse ReactionDocetaxel 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%) 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]) 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 ReactionAnyGrade 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 Docetaxel 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 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 75 mg/m2 + cisplatin 75 mg/m2 + fluorouracil 750 mg/m2
n=221
Cisplatin 100 mg/m2 + fluorouracil 1,000 mg/m2
n=224
Adverse ReactionAny %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/ odynophagia162145
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 Docetaxel In Head And Neck Cancer

Table 11 summarizes the safety data obtained from patients that received induction chemotherapy with docetaxel 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 in Combination with Cisplatin and Fluorouracil Followed by Radiotherapy (TAX323) or Chemoradiotherapy (TAX324)

TAX323
(n=355)
TAX324
(n=494)
Docetaxel arm
(n=174)
Comparator arm
(n=181)
Docetaxel 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 %
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 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 has been reported in patients treated with docetaxel in combination regimens including doxorubicin, 5fluorouracil and/or cyclophosphamide, and 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 have been reported.

Gastrointestinal: enterocolitis, including colitis, ischemic colitis, and neutropenic enterocolitis, has been reported with a 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.

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

Hematologic: bleeding episodes. Disseminated intravascular coagulation (DIC), often in association with sepsis or multiorgan failure, has been reported.

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

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

Metabolism and nutrition disorders: electrolyte imbalance, including hyponatremia, hypokalemia, hypomagnesemia, and hypocalcemia has been reported.

Neurologic: confusion, 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. 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. Cystoid macular edema (CME) have been reported in patients treated with docetaxel.

Respiratory: dyspnea, acute pulmonary edema, acute respiratory distress syndrome/pneumonitis, interstitial lung disease, interstitial pneumonia, respiratory failure, and pulmonary fibrosis have been reported and may be associated with fatal outcome. Radiation pneumonitis has 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.

Second primary malignancies: second primary malignancies, including AML, MDS, NHL, and renal cancer, have been reported in patients treated with DOCETAXEL INJECTION-containing regimens [see WARNINGS AND PRECAUTIONS].

Read the entire FDA prescribing information for Docefrez (docetaxel)

© Docefrez Patient Information is supplied by Cerner Multum, Inc. and Docefrez Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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