A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Taxotere Side Effects, and Drug Interactions - Docetaxel
Taxotere Side Effects, and Drug Interactions - Docetaxel
SIDE EFFECTS
Adverse reactions are described for TAXOTERE according to indication:
-in the treatment of breast cancer, at the maximum dose of 100 mg/m2
-in the adjuvant therapy of breast cancer at a dose of 75 mg/m2,
in combination with doxorubicin and cyclophosphamide
-in the treatment of advanced non-small cell lung cancer after prior platinum-based
chemotherapy, at a dose of 75 mg/m2
-in the treatment of non-small cell lung cancer in patients who have not
previously received chemotherapy for this condition, at a dose of 75 mg/m2,
in combination with cisplatin
-in the treatment of androgen independent (hormone refractory) metastatic
prostate cancer, at a dose of 75 mg/m2 every three weeks in combination
with prednisone
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.
|
Summary of Adverse Events in Patients Receiving TAXOTERE
at 100 mg/m2
|
|
Adverse Event
|
All Tumor Types Normal LFTs* n=2045 %
|
All Tumor Types Elevated LFTs** n=61 %
|
Breast Cancer Normal LFTs* n=965 %
|
|
Hematologic
|
|
|
|
|
Neutropenia
|
|
|
|
|
<2000 cells/mm3
|
95.5
|
96.4
|
98.5
|
|
<500 cells/mm3
|
75.4
|
87.5
|
85.9
|
|
Leukopenia
|
|
|
|
|
<4000 cells/mm3
|
95.6
|
98.3
|
98.6
|
|
<1000 cells/mm3
|
31.6
|
46.6
|
43.7
|
|
Thrombocytopenia
|
|
|
|
|
<100,000 cells/mm3
|
8.0
|
24.6
|
9.2
|
|
Anemia
|
|
|
|
|
<11 g/dL
|
90.4
|
91.8
|
93.6
|
|
<8 g/dL
|
8.8
|
31.1
|
7.7
|
|
Febrile Neutropenia***
|
11.0
|
26.2
|
12.3
|
|
Septic Death
|
1.6
|
4.9
|
1.4
|
|
Non-Septic Death Infections
|
0.6
|
6.6
|
0.6
|
|
Any
|
21.6
|
32.8
|
22.2
|
|
Severe
|
6.1
|
16.4
|
6.4
|
|
Fever in Absence of Infection
|
|
|
|
|
Any
|
31.2
|
41.0
|
35.1
|
|
Severe
|
2.1
|
8.2
|
2.2
|
|
Hypersensitivity Reactions
|
|
|
|
|
Regardless of Premedication
|
|
|
|
|
Any
|
21.0
|
19.7
|
17.6
|
|
Severe
|
4.2
|
9.8
|
2.6
|
|
With 3-day Premedication
|
n=92
|
n=3
|
n=92
|
|
Any
|
15.2
|
33.3
|
15.2
|
|
Severe
|
2.2
|
0
|
2.2
|
|
Fluid Retention
|
|
|
|
|
Regardless of Premedication
|
|
|
|
|
Any
|
47.0
|
39.3
|
59.7
|
|
Severe
|
6.9
|
8.2
|
8.9
|
|
With 3-day Premedication
|
n=92
|
n=3
|
n=92
|
|
Any
|
64.1
|
66.7
|
64.1
|
|
Severe
|
6.5
|
33.3
|
6.5
|
|
Neurosensory
|
|
|
|
|
Any
|
49.3
|
34.4
|
58.3
|
|
Severe
|
4.3
|
0
|
5.5
|
|
Cutaneous
|
|
|
|
|
Any
|
47.6
|
54.1
|
47.0
|
|
Severe
|
4.8
|
9.8
|
5.2
|
|
Nail Changes
|
|
|
|
|
Any
|
30.6
|
23.0
|
40.5
|
|
Severe
|
2.5
|
4.9
|
3.7
|
|
Gastrointestinal
|
|
|
|
|
Nausea
|
38.8
|
37.7
|
42.1
|
|
Vomiting
|
22.3
|
23.0
|
23.4
|
|
Diarrhea
|
38.7
|
32.8
|
42.6
|
|
Severe
|
4.7
|
4.9
|
5.5
|
|
Stomatitis
|
|
|
|
|
Any
|
41.7
|
49.2
|
51.7
|
|
Severe
|
5.5
|
13.0
|
7.4
|
|
Alopecia
|
75.8
|
62.3
|
74.2
|
|
Asthenia
|
|
|
|
|
Any
|
61.8
|
52.5
|
66.3
|
|
Severe
|
12.8
|
24.6
|
14.9
|
|
Myalgia
|
|
|
|
|
Any
|
18.9
|
16.4
|
21.1
|
|
Severe
|
1.5
|
1.6
|
1.8
|
|
Arthralgia
|
9.2
|
6.6
|
8.2
|
|
Infusion Site Reactions
|
4.4
|
3.3
|
4.0
|
|
*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: SGOT and/or SGPT > 1.5 times
ULN concurrent with alkaline phosphatase > 2.5 times ULN
|
|
***Febrile Neutropenia: ANC grade 4 with fever > antibiotics
and/or hospitalization
|
Hematologic: (see WARNINGS).
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
> otics 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: Premedication Regimen,
and PRECAUTIONS sections).
Cutaneous: Severe skin toxicity is discussed
in 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 PRECAUTIONS).
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.)
Combination Therapy with TAXOTERE in the Adjuvant Treatment
of Breast Cancer
The following table presents treatment emergent adverse events
(TEAEs) observed in 744 patients, who were treated with TAXOTERE 75 mg/m2
every 3 weeks in combination with doxorubicin and cyclophosphamide.
|
Clinically Important Treatment Emergent Adverse Events
Regardless of Causal Relationship in Patients Receiving TAXOTERE in Combination
with Doxorubicin and Cyclophosphamide (TAX 316).
|
|
|
TAXOTERE 75 mg/m2+ Doxorubicin 50 mg/m2+
Cyclophosphamide 500 mg/m n=744 2 (TAC) %
|
Fluorouracil 500 mg/m2+ Doxorubicin 50 mg/m2+
Cyclophosphamide 500 mg/m 2 (FAC) n=736%
|
|
Adverse Event
|
Any
|
G 3/4
|
Any
|
G 3/4
|
|
Anemia
|
91.5
|
4.3
|
71.7
|
1.6
|
|
Neutropenia
|
71.4
|
65.5
|
82.0
|
49.3
|
|
Fever in absence of infection
|
46.5
|
1.3
|
17.1
|
0.0
|
|
Infection
|
39.4
|
3.9
|
36.3
|
2.2
|
|
Thrombocytopenia
|
39.4
|
2.0
|
27.7
|
1.2
|
|
Febrile neutropenia
|
24.7
|
N/A
|
2.5
|
N/A
|
|
Neutropenic infection
|
12.1
|
N/A
|
6.3
|
N/A
|
|
Hypersensitivity reactions
|
13.4
|
1.3
|
3.7
|
0.1
|
|
Lymphedema
|
4.4
|
0.0
|
1.2
|
0.0
|
|
Fluid Retention*
|
35.1
|
0.9
|
14.7
|
0.1
|
|
Peripheral edema
|
26.9
|
0.4
|
7.3
|
0.0
|
|
Weight gain
|
12.9
|
0.3
|
8.6
|
0.3
|
|
Neuropathy sensory
|
25.5
|
0.0
|
10.2
|
0.0
|
|
Neuro-cortical
|
5.1
|
0.5
|
6.4
|
0.7
|
|
Neuropathy motor
|
3.8
|
0.1
|
2.2
|
0.0
|
|
Neuro-cerebellar
|
2.4
|
0.1
|
2.0
|
0.0
|
|
Syncope
|
1.6
|
0.5
|
1.2
|
0.3
|
|
Alopecia
|
97.8
|
N/A
|
97.1
|
N/A
|
|
Skin toxicity
|
26.5
|
0.8
|
17.7
|
0.4
|
|
Nail disorders
|
18.5
|
0.4
|
14.4
|
0.1
|
|
Nausea
|
80.5
|
5.1
|
88.0
|
9.5
|
|
Stomatitis
|
69.4
|
7.1
|
52.9
|
2.0
|
|
Vomiting
|
44.5
|
4.3
|
59.2
|
7.3
|
|
Diarrhea
|
35.2
|
3.8
|
27.9
|
1.8
|
|
Constipation
|
33.9
|
1.1
|
31.8
|
1.4
|
|
Taste perversion
|
27.8
|
0.7
|
15.1
|
0.0
|
|
Anorexia
|
21.6
|
2.2
|
17.7
|
1.2
|
|
Abdominal Pain
|
10.9
|
0.7
|
5.3
|
0.0
|
|
Amenorrhea
|
61.7
|
N/A
|
52.4
|
N/A
|
|
Cough
|
13.7
|
0.0
|
9.8
|
0.1
|
|
Cardiac dysrhythmias
|
7.9
|
0.3
|
6.0
|
0.3
|
|
Vasodilatation
|
27.0
|
1.1
|
21.2
|
0.5
|
|
Hypotension
|
2.6
|
0.0
|
1.1
|
0.1
|
|
Phlebitis
|
1.2
|
0.0
|
0.8
|
0.0
|
|
Asthenia
|
80.8
|
11.2
|
71.2
|
5.6
|
|
Myalgia
|
26.7
|
0.8
|
9.9
|
0.0
|
|
Arthralgia
|
19.4
|
0.5
|
9.0
|
0.3
|
|
Lacrimation disorder
|
11.3
|
0.1
|
7.1
|
0.0
|
|
Conjunctivitis
|
5.1
|
0.3
|
6.9
|
0.1
|
|
* 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 events, 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 (1.6% vs. 0.5%). One patient in each arm died due to
heart failure.
Acute Myeloid Leukemia
Treatment-related acute myeloid leukemia (AML) 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.
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 below. 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
otherwise noted.
|
Treatment Emergent Adverse Events Regardless of Relationship
to Treatment in Patients Receiving TAXOTERE as Monotherapy for Non-Small
Cell Lung Cancer Previously Treated with Platinum-Based Chemotherapy*
|
|
Adverse Event
|
TAXOTERE 75 mg/m2 n=176 %
|
Best Supportive Care n=49 %
|
Vinorelbine/ Ifosfamide n=119 %
|
|
Neutropenia
|
|
Any
|
84.1
|
14.3
|
83.2
|
|
Grade 3/4
|
65.3
|
12.2
|
57.1
|
|
Leukopenia
|
|
|
|
|
Any
|
83.5
|
6.1
|
89.1
|
|
Grade 3/4
|
49.4
|
0
|
42.9
|
|
Thrombocytopenia
|
|
Any
|
8.0
|
0
|
7.6
|
|
Grade 3/4
|
2.8
|
0
|
1.7
|
|
Anemia
|
|
Any
|
91.0
|
55.1
|
90.8
|
|
Grade 3/4
|
9.1
|
12.2
|
14.3
|
|
Febrile Neutropenia**
|
6.3
|
NA†
|
0.8
|
|
Infection
|
|
Any
|
33.5
|
28.6
|
30.3
|
|
Grade 3/4
|
10.2
|
6.1
|
9.2
|
|
Treatment Related Mortality
|
2.8
|
NA†
|
3.4
|
|
HypersensitivityReactions
|
|
Any
|
5.7
|
0
|
0.8
|
|
Grade 3/4
|
2.8
|
0
|
0
|
|
Fluid Retention
|
|
Any
|
33.5
|
ND††
|
22.7
|
|
Severe
|
2.8
|
|
3.4
|
|
Neurosensory
|
|
Any
|
23.3
|
14.3
|
28.6
|
|
Grade 3/4
|
1.7
|
6.1
|
5.0
|
|
Neuromotor
|
|
Any
|
15.9
|
8.2
|
10.1
|
|
Grade 3/4
|
4.5
|
6.1
|
3.4
|
|
Skin
|
|
Any
|
19.9
|
6.1
|
16.8
|
|
Grade 3/4
|
0.6
|
2.0
|
0.8
|
|
Gastrointestinal
|
|
Nausea
|
|
|
|
|
Any
|
33.5
|
30.6
|
31.1
|
|
Grade 3/4
|
5.1
|
4.1
|
7.6
|
|
Vomiting
|
|
|
|
|
Any
|
21.6
|
26.5
|
21.8
|
|
Grade 3/4
|
2.8
|
2.0
|
5.9
|
|
Diarrhea
|
|
|
|
|
Any
|
22.7
|
6.1
|
11.8
|
|
Grade 3/4
|
2.8
|
0
|
4.2
|
|
Alopecia
|
56.3
|
34.7
|
49.6
|
|
Asthenia
|
|
Any
|
52.8
|
57.1
|
53.8
|
|
Severe***
|
18.2
|
38.8
|
22.7
|
|
Stomatitis
|
|
Any
|
26.1
|
6.1
|
7.6
|
|
Grade 3/4
|
1.7
|
0
|
0.8
|
|
Pulmonary
|
|
Any
|
40.9
|
49.0
|
45.4
|
|
Grade 3/4
|
21.0
|
28.6
|
18.5
|
|
Nail Disorder
|
|
Any
|
11.4
|
0
|
1.7
|
|
Severe***
|
1.1
|
0
|
0
|
|
Myalgia
|
|
Any
|
6.3
|
0
|
2.5
|
|
Severe***
|
0
|
0
|
0
|
|
Arthralgia
|
|
Any
|
3.4
|
2.0
|
1.7
|
|
Severe***
|
0
|
0
|
0.8
|
|
Taste Perversion
|
|
Any
|
5.7
|
0
|
0
|
|
Severe***
|
0.6
|
0
|
0
|
|
*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 > otics
and/or hospitalization
|
|
***COSTART term and grading system
|
|
†Not Applicable; ††Not
Done
|
Combination Therapy with TAXOTERE in Chemotherapy-Naïve
Advanced Unresectable or Metastatic NSCLC
The table below 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.
|
Adverse Events Regardless of Relationship to Treatment
in Chemotherapy-Naïve Advanced Non-Small Cell Lung Cancer Patients
Receiving TAXOTERE in Combination with Cisplatin
|
|
Adverse Event
|
TAXOTERE 75 mg/m2 + Cisplatin 75 mg/m2
n=406 %
|
Vinorelbine 25 mg/m2 + Cisplatin 100 mg/m2
n=396 %
|
|
Neutropenia
|
|
|
|
Any
|
91
|
90
|
|
Grade 3/4
|
74
|
78
|
|
Febrile Neutropenia
|
5
|
5
|
|
Thrombocytopenia
|
|
|
|
Any
|
15
|
15
|
|
Grade 3/4
|
3
|
4
|
|
Anemia
|
|
|
|
Any
|
89
|
94
|
|
Grade 3/4
|
7
|
25
|
|
Infection
|
|
|
|
Any
|
35
|
37
|
|
Grade 3/4
|
8
|
8
|
|
Fever in absence of infection
|
|
|
|
Any
|
33
|
29
|
|
Grade 3/4
|
< 1
|
1
|
|
Hypersensitivity Reaction*
|
|
|
|
Any
|
12
|
4
|
|
Grade 3/4
|
3
|
< 1
|
|
Fluid Retention**
|
|
|
|
Any
|
54
|
42
|
|
All severe or life-
|
2
|
2
|
|
threatening events
|
|
|
|
Pleural effusion
|
|
|
|
Any
|
23
|
22
|
|
All severe or life- threatening events
|
2
|
2
|
|
Peripheral edema
|
|
|
|
Any
|
34
|
18
|
|
All severe or life- threatening events
|
<1
|
<1
|
|
Weight gain
|
|
|
|
Any
|
15
|
9
|
|
All severe or life- threatening events
|
<1
|
<1
|
|
Neurosensory
|
|
|
|
Any
|
47
|
42
|
|
Grade 3/4
|
4
|
4
|
|
Neuromotor
|
|
|
|
Any
|
19
|
17
|
|
Grade 3/4
|
3
|
6
|
|
Skin
|
|
|
|
Any
|
16
|
14
|
|
Grade 3/4
|
<1
|
1
|
|
Nausea
|
|
|
|
Any
|
72
|
76
|
|
Grade 3/4
|
10
|
17
|
|
Vomiting
|
|
|
|
Any
|
55
|
61
|
|
Grade 3/4
|
8
|
16
|
|
Diarrhea
|
|
|
|
Any
|
47
|
25
|
|
Grade 3/4
|
7
|
3
|
|
Anorexia**
|
|
|
|
Any
|
42
|
40
|
|
All severe or life-
|
5
|
5
|
|
threatening events
|
|
|
|
Stomatitis
|
|
|
|
Any
|
24
|
21
|
|
Grade 3/4
|
2
|
1
|
|
Alopecia
|
|
|
|
Any
|
75
|
42
|
|
Grade 3
|
< 1
|
0
|
|
Asthenia**
|
|
|
|
Any
|
74
|
75
|
|
All severe or life-
|
12
|
14
|
|
threatening events
|
|
|
|
Nail Disorder**
|
|
|
|
Any
|
14
|
< 1
|
|
All severe events
|
< 1
|
0
|
|
Myalgia**
|
|
|
|
Any
|
18
|
12
|
|
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
vinorel-bine+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 section)
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.
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.
|
Clinically Important Treatment Emergent Adverse Events
(Regardless of Relationship) in Patients with Prostate Cancer who Received
TAXOTERE in Combination with Prednisone (TAX 327)
|
|
|
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 Event
|
Any
|
G 3/4
|
Any
|
G 3/4
|
|
Anemia
|
66.5
|
4.9
|
57.8
|
1.8
|
|
Neutropenia
|
40.9
|
32.0
|
48.2
|
21.7
|
|
Thrombocytopenia
|
3.4
|
0.6
|
7.8
|
1.2
|
|
Febrile neutropenia
|
2.7
|
N/A
|
1.8
|
N/A
|
|
Infection
|
32.2
|
5.7
|
20.3
|
4.2
|
|
Epistaxis
|
5.7
|
0.3
|
1.8
|
0.0
|
|
Allergic Reactions
|
8.4
|
0.6
|
0.6
|
0.0
|
|
Fluid Retention*
|
24.4
|
0.6
|
4.5
|
0.3
|
|
Weight Gain*
|
7.5
|
0.3
|
3.0
|
0.0
|
|
Peripheral Edema*
|
18.1
|
0.3
|
1.5
|
0.0
|
|
Neuropathy Sensory
|
30.4
|
1.8
|
7.2
|
0.3
|
|
Neuropathy Motor
|
7.2
|
1.5
|
3.0
|
0.9
|
|
Rash/Desquamation
|
6.0
|
0.3
|
3.3
|
0.6
|
|
Alopecia
|
65.1
|
N/A
|
12.8
|
N/A
|
|
Nail Changes
|
29.5
|
0.0
|
7.5
|
0.0
|
|
Nausea
|
41.0
|
2.7
|
35.5
|
1.5
|
|
Diarrhea
|
31.6
|
2.1
|
9.6
|
1.2
|
|
Stomatitis/Pharyngitis
|
19.6
|
0.9
|
8.4
|
0.0
|
|
Taste Disturbance
|
18.4
|
0.0
|
6.6
|
0.0
|
|
Vomiting
|
16.9
|
1.5
|
14.0
|
1.5
|
|
Anorexia
|
16.6
|
1.2
|
14.3
|
0.3
|
|
Cough
|
12.3
|
0.0
|
7.8
|
0.0
|
|
Dyspnea
|
15.1
|
2.7
|
8.7
|
0.9
|
|
Cardiac left ventricular function
|
9.6
|
0.3
|
22.1
|
1.2
|
|
Fatigue
|
53.3
|
4.5
|
34.6
|
5.1
|
|
Myalgia
|
14.5
|
0.3
|
12.8
|
0.9
|
|
Tearing
|
9.9
|
0.6
|
1.5
|
0.0
|
|
Arthralgia
|
8.1
|
0.6
|
5.1
|
1.2
|
|
* Related to treatment
|
Post-marketing Experiences
The following adverse events 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, tachy-cardia,
myocardial infarction
Cutaneous: rare cases of bullous eruption such as erythema
multiforme or Stevens-Johnson syndrome. Multiple factors may have contributed
to the development of these effects.
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
Hepatic: rare cases of hepatitis 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.
Respiratory: dyspnea, acute pulmonary edema, acute respiratory
distress syndrome, interstitial pneumonia. Pulmonary fibrosis has been rarely
reported.
Urogenital: renal insufficiency
DRUG INTERACTIONS
There have been no formal clinical studies to evaluate the
drug interactions of TAXOTERE with other medications. 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, such as cyclosporine, terfenadine, ketoconazole, erythromycin, and
troleandomycin. Caution should be exercised with these drugs when treating patients
receiving TAXOTERE as there is a potential for a significant interaction.
top
