Docetaxel in Breast Cancer
Study Details
Study Description
Brief Summary
Primary objective :
- To compare disease-free survival after treatment with docetaxel in combination with doxorubicin and cyclophosphamide to doxorubicin and cyclophosphamide followed by docetaxel in operable adjuvant breast cancer HER2neu negative patients with positive axillary lymph nodes.
Secondary objectives :
-
To compare toxicity and quality of life between the 2 above-mentioned arms.
-
To evaluate pathologic and molecular markers for predicting efficacy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1 Doxorubicin in combination with cyclophosphamide followed by docetaxel (AC -> T) |
Drug: Docetaxel,doxorubicin, cyclophosphamide
AC x 4: Doxorubicin 60 mg/m² as an IV bolus in combination with cyclophosphamide 600 mg/m² as IV followed by docetaxel 100 mg/m² as 1 hour IV infusion on day 1 every 3 weeks for 4 cycles.
|
| Experimental: 2 Docetaxel in combination with doxorubicin and cyclophosphamide (TAC) |
Drug: docetaxel, doxorubicin, cyclophosphamide
TAC x 6 : Docetaxel 75 mg/m² as 1 hour IV infusion on day 1 every 3 weeks in combination with doxorubicin 50 mg/m² as an IV bolus and cyclophosphamide 500 mg/m2 as IV on day 1 every 3 weeks. Sequence of administration is as follows: doxorubicin followed by cyclophosphamide followed by docetaxel.
|
Outcome Measures
Primary Outcome Measures
- Local, Regional or Metastatic Relapse, or Second Primary Cancer, or Death From Any Cause (Disease-Free Survival) [Median follow-up 65 months]
The primary event is the local, regional or metastatic relapse or the date of second primary cancer or death from any cause (whichever occurs first). The primary efficacy analysis is performed on the time from randomization to this primary event. The Measured Values table below presents the numbers of patients with the event at the end of the study period.
Secondary Outcome Measures
- Death From Any Cause (Overall Survival) [Median follow-up of 65 months]
The considered event is death from any cause. The analysis is performed on the time from randomization to this event. The Measured Values table below presents the numbers of patients with the event at the end of the study period.
Eligibility Criteria
Criteria
Inclusion Criteria :
-
Histologically proven breast cancer. Interval between definitive surgery that includes axillary lymph node dissection and registration is less than or equal to 60 days. A central pathology review may be performed post randomization for confirmation of diagnosis and molecular studies.
-
Definitive surgical treatment must be either mastectomy, or breast conserving surgery with axillary lymph node dissection for operable breast cancer (T1-3, Clinical N0-1, M0). Margins of resected specimen from definitive surgery must be histologically free of invasive adenocarcinoma and Ductal Carcinoma In Situ (DCIS). Lobular carcinoma in-situ does not count as a positive margin.
-
Histologic examination of the tumor: Invasive adenocarcinoma with at least one axillary lymph node (pN1) showing evidence of tumor among a minimum of six resected lymph nodes.
-
Tumor must show negative HER2 neu proto-oncogene overexpression by FISH (Fluorescence In Situ Hybridization). Confirmation of non overexpression will be centrally assessed by authorized BCIRG (Breast Cancer International Research Group) laboratories prior to randomization.
-
Estrogen and/or progesterone receptor analysis performed on the primary tumor prior to randomization. Results must be known at the time of randomization.(Note: Patients whose tumor is estrogen receptor negative with progesterone receptor status unknown or undetermined, must have the progesterone receptor assayed in order to determine hormonal receptor status. Patients whose tumor is progesterone receptor negative with estrogen receptor status unknown or undetermined, must have the estrogen receptor assayed in order to determine hormonal receptor status).
-
Karnofsky Performance status index > 80%.
-
Normal cardiac function must be confirmed by LVEF (Lef Ventricular Ejection Fraction) i.e. MUGA (Multi Gated Acquisition) scan or echocardiography and ECG within 3 months prior to registration. LVEF result must be above or equal to the lower limit of normal for the institution. The ECG results must be within normal limits or show no significant abnormalities.
-
Laboratory requirements: (within 14 days prior to registration)
-
Hematology:
-
Neutrophils > or = 2.0 x 10^9/L
-
Platelets > or = 100 x 10^9/L
-
Hemoglobin > or = 10 g/dL
-
Hepatic function:
-
Total bilirubin < or = 1 UNL (Upper Normal Limit)
-
ASAT (Aspartate Amino Transferase) and ALAT (Alanine Amino Transferase) < or = 2.5 UNL
-
Alkaline phosphatase < or = 5 UNL
-
Patients with ASAT and/or ALAT > 1.5 x UNL associated with alkaline phosphatase > 2.5 x UNL are not eligible for the study.
-
Renal function:
-
Creatinine < or = 175 µmol/L (2 mg/dL);
-
If limit reached, the calculated creatinine clearance should be > or = 60mL/min.
-
Complete staging work-up within 3 months prior to registration. All patients will have contralateral mammography, chest X-ray (Posteroanterior and lateral) and/or CT scan and/or MRI (Magnetic Resonance Imaging), abdominal ultrasound and/or CT scan (computerized tomography) and/or MRI, and bone scan. In case of positive bone scan, bone X-ray is mandatory to rule out the possibility of non-metastatic hot spots. Other tests may be performed as clinically indicated.
-
Negative pregnancy test (urine or serum) within 7 days prior to registration for all women of childbearing potential.
Exclusion Criteria :
-
Prior systemic anticancer therapy for breast cancer (immunotherapy, hormonotherapy, genetherapy , chemotherapy).
-
Prior anthracycline therapy or taxoids (paclitaxel, docetaxel) for any malignancy.
-
Prior radiation therapy for breast cancer.
-
Bilateral invasive breast cancer.
-
Pregnant, or lactating patients. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures during study treatment (chemotherapy and tamoxifen therapy) and must have negative urine or serum pregnancy test within 7 days prior to registration.
-
Any T4 or N2 or known N3 or M1 breast cancer.
-
Pre-existing motor or sensory neurotoxicity of a severity > grade 2 by NCI-CTC (National Cancer Institute - Common Toxicity Criteria), version 2.0.
-
Other serious illness or medical condition:
-
congestive heart failure or unstable angina pectoris, previous history of myocardial infarction within 1 year from study entry, uncontrolled hypertension or high-risk uncontrolled arrhythmias
-
history of significant neurologic or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent
-
active uncontrolled infection
-
active peptic ulcer, unstable diabetes mellitus
-
Past or current history of neoplasm other than breast carcinoma, except for:
-
curatively treated non-melanoma skin cancer
-
carcinoma in situ of the cervix
-
other cancer curatively treated and with no evidence of disease for at least 10 years
-
ipsilateral ductal carcinoma in-situ (DCIS) of the breast
-
lobular carcinoma in-situ (LCIS) of the breast
-
Chronic treatment with corticosteroids unless initiated > 6 months prior to study entry and at low dose (< 20 mg methylprednisolone or equivalent).
-
Concurrent treatment with ovarian hormonal replacement therapy. Prior treatment should be stopped before study entry.
-
Definite contraindications for the use of corticosteroids.
-
Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry.
-
Concurrent treatment with any other anti-cancer therapy.
-
Current therapy with any hormonal agent such as raloxifene, tamoxifen or other selective estrogen receptor modulators (SERMs), either for osteoporosis or prevention. Patients must have discontinued these agents prior to randomization.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sanofi-Aventis | Bridgewater | New Jersey | United States | 08807 |
| 2 | Sanofi-Aventis | Buenos Aires | Argentina | ||
| 3 | Sanofi-Aventis | Macquarie Park | Australia | ||
| 4 | Sanofi-Aventis | Brussels | Belgium | ||
| 5 | Sanofi-Aventis | Sarajevo | Bosnia and Herzegovina | ||
| 6 | Sanofi-Aventis | Sao Paulo | Brazil | ||
| 7 | Sanofi-Aventis | Sofia | Bulgaria | ||
| 8 | Sanofi-Aventis | Laval | Canada | ||
| 9 | Sanofi-Aventis | Shanghai | China | ||
| 10 | Sanofi-Aventis | Bogota | Colombia | ||
| 11 | Sanofi-Aventis | Zagreb | Croatia | ||
| 12 | Sanofi-Aventis | Nikosia | Cyprus | ||
| 13 | Sanofi-Aventis | Praha | Czech Republic | ||
| 14 | Sanofi-Aventis | Cairo | Egypt | ||
| 15 | Sanofi-Aventis | Tallin | Estonia | ||
| 16 | Sanofi-Aventis | Paris | France | ||
| 17 | Sanofi-Aventis | Berlin | Germany | ||
| 18 | Sanofi-Aventis | Kallithea | Greece | ||
| 19 | Sanofi-Aventis | Hong Kong | Hong Kong | ||
| 20 | Sanofi-Aventis | Budapest | Hungary | ||
| 21 | Sanofi-Aventis | Dublin | Ireland | ||
| 22 | Sanofi-Aventis | Natanya | Israel | ||
| 23 | Sanofi-Aventis | Seoul | Korea, Republic of | ||
| 24 | Sanofi-Aventis | Beirut | Lebanon | ||
| 25 | Sanofi-Aventis | Mexico | Mexico | ||
| 26 | Sanofi-aventis | Auckland | New Zealand | ||
| 27 | Sanofi-Aventis | Warsaw | Poland | ||
| 28 | Sanofi-Aventis | Porto Salvo | Portugal | ||
| 29 | Sanofi-Aventis | Bucuresti | Romania | ||
| 30 | Sanofi-Aventis | Moscow | Russian Federation | ||
| 31 | Sanofi-Aventis | Jeddah | Saudi Arabia | ||
| 32 | Sanofi-Aventis | Ljubljana | Slovenia | ||
| 33 | Sanofi-Aventis | Midrand | South Africa | ||
| 34 | Sanofi-Aventis | Barcelona | Spain | ||
| 35 | Sanofi-Aventis | Taipei | Taiwan | ||
| 36 | Sanofi-Aventis | Montevideo | Uruguay | ||
| 37 | Sanofi-Aventis | Caracas | Venezuela |
Sponsors and Collaborators
- Sanofi
- Cancer International Research Group (CIRG)
Investigators
- Study Director: Jean-Philippe AUSSEL, Sanofi
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TAX_GMA_301
- BCIRG 005
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Doxorubicin + Cyclophosphamide Followed by Docetaxel (AC -> T) | Docetaxel + Doxorubicin and Cyclophosphamide (TAC) |
|---|---|---|
| Arm/Group Description | AC x 4: Doxorubicin 60 mg/m² as an IV bolus in combination with cyclophosphamide 600 mg/m² as IV followed by docetaxel 100 mg/m² as 1 hour IV infusion on day 1 every 3 weeks for 4 cycles. | TAC x 6 : Docetaxel 75 mg/m² as 1 hour IV infusion on day 1 every 3 weeks in combination with doxorubicin 50 mg/m² as an IV bolus and cyclophosphamide 500 mg/m2 as IV on day 1 every 3 weeks. Sequence of administration is as follows: doxorubicin followed by cyclophosphamide followed by docetaxel. |
| Period Title: Overall Study | ||
| STARTED | 1649 | 1649 |
| COMPLETED | 1477 | 1526 |
| NOT COMPLETED | 172 | 123 |
Baseline Characteristics
| Arm/Group Title | Doxorubicin + Cyclophosphamide Followed by Docetaxel (AC -> T) | Docetaxel + Doxorubicin and Cyclophosphamide (TAC) | Total |
|---|---|---|---|
| Arm/Group Description | AC x 4: Doxorubicin 60 mg/m² as an IV bolus in combination with cyclophosphamide 600 mg/m² as IV followed by docetaxel 100 mg/m² as 1 hour IV infusion on day 1 every 3 weeks for 4 cycles. | TAC x 6 : Docetaxel 75 mg/m² as 1 hour IV infusion on day 1 every 3 weeks in combination with doxorubicin 50 mg/m² as an IV bolus and cyclophosphamide 500 mg/m2 as IV on day 1 every 3 weeks. Sequence of administration is as follows: doxorubicin followed by cyclophosphamide followed by docetaxel. | Total of all reporting groups |
| Overall Participants | 1649 | 1649 | 3298 |
| Age, Customized (Number) [Number] | |||
| > =65 years |
85
5.2%
|
83
5%
|
168
5.1%
|
| Between 65 and 50 years |
784
47.5%
|
783
47.5%
|
1567
47.5%
|
| Between 49 and 35 years |
689
41.8%
|
710
43.1%
|
1399
42.4%
|
| < =35 years |
91
5.5%
|
73
4.4%
|
164
5%
|
| Age (years) [Median (Full Range) ] | |||
| Median (Full Range) [years] |
50
|
50
|
50
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
1649
100%
|
1649
100%
|
3298
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||
| Argentina |
31
1.9%
|
32
1.9%
|
63
1.9%
|
| Australia |
156
9.5%
|
144
8.7%
|
300
9.1%
|
| Belgium |
33
2%
|
31
1.9%
|
64
1.9%
|
| Bosnia And Herzegovina |
5
0.3%
|
5
0.3%
|
10
0.3%
|
| Brazil |
19
1.2%
|
21
1.3%
|
40
1.2%
|
| Bulgaria |
11
0.7%
|
11
0.7%
|
22
0.7%
|
| Canada |
174
10.6%
|
180
10.9%
|
354
10.7%
|
| China |
21
1.3%
|
17
1%
|
38
1.2%
|
| Colombia |
6
0.4%
|
8
0.5%
|
14
0.4%
|
| Croatia |
29
1.8%
|
29
1.8%
|
58
1.8%
|
| Cyprus |
2
0.1%
|
5
0.3%
|
7
0.2%
|
| Czech Republic |
11
0.7%
|
10
0.6%
|
21
0.6%
|
| Egypt |
4
0.2%
|
4
0.2%
|
8
0.2%
|
| Estonia |
3
0.2%
|
2
0.1%
|
5
0.2%
|
| France |
59
3.6%
|
58
3.5%
|
117
3.5%
|
| Germany |
224
13.6%
|
223
13.5%
|
447
13.6%
|
| Greece |
5
0.3%
|
3
0.2%
|
8
0.2%
|
| Hong Kong |
3
0.2%
|
6
0.4%
|
9
0.3%
|
| Hungary |
34
2.1%
|
35
2.1%
|
69
2.1%
|
| Ireland |
83
5%
|
88
5.3%
|
171
5.2%
|
| Israel |
63
3.8%
|
67
4.1%
|
130
3.9%
|
| Lebanon |
23
1.4%
|
18
1.1%
|
41
1.2%
|
| Mexico |
5
0.3%
|
3
0.2%
|
8
0.2%
|
| New Zealand |
21
1.3%
|
19
1.2%
|
40
1.2%
|
| Poland |
167
10.1%
|
168
10.2%
|
335
10.2%
|
| Portugal |
2
0.1%
|
1
0.1%
|
3
0.1%
|
| Russian Federation |
32
1.9%
|
35
2.1%
|
67
2%
|
| Romania |
17
1%
|
19
1.2%
|
36
1.1%
|
| Saudi Arabia |
2
0.1%
|
0
0%
|
2
0.1%
|
| Slovenia |
15
0.9%
|
17
1%
|
32
1%
|
| South Africa |
19
1.2%
|
21
1.3%
|
40
1.2%
|
| South Korea |
22
1.3%
|
27
1.6%
|
49
1.5%
|
| Spain |
26
1.6%
|
41
2.5%
|
67
2%
|
| Taiwan |
18
1.1%
|
16
1%
|
34
1%
|
| United States |
294
17.8%
|
278
16.9%
|
572
17.3%
|
| Uruguay |
4
0.2%
|
2
0.1%
|
6
0.2%
|
| Venezuela |
6
0.4%
|
5
0.3%
|
11
0.3%
|
| Hormonal Receptor Status (Number) [Number] | |||
| Positive |
1348
81.7%
|
1346
81.6%
|
2694
81.7%
|
| Negative |
301
18.3%
|
303
18.4%
|
604
18.3%
|
| Karnofsky Performance Status at Baseline (Number) [Number] | |||
| 80 - Activity with effort; some signs of disease |
36
2.2%
|
33
2%
|
69
2.1%
|
| 90 - Normal activity; minor signs of disease |
315
19.1%
|
323
19.6%
|
638
19.3%
|
| 100 - Normal no complaints; no evidence of disease |
1298
78.7%
|
1293
78.4%
|
2591
78.6%
|
| Menopausal status (Number) [Number] | |||
| Pre-Menopausal or Other age < 50 Years |
866
52.5%
|
863
52.3%
|
1729
52.4%
|
| Post-Menopausal or Other age > 50 Years |
783
47.5%
|
786
47.7%
|
1569
47.6%
|
| Number of Positive Lymph Nodes (Number) [Number] | |||
| [0] |
0
0%
|
1
0.1%
|
1
0%
|
| [1 to 3] |
1010
61.2%
|
1005
60.9%
|
2015
61.1%
|
| [4 to 10] |
462
28%
|
456
27.7%
|
918
27.8%
|
| > 10 |
177
10.7%
|
187
11.3%
|
364
11%
|
| Patients with at least one surgery (Number) [Number] | |||
| Mastectomy |
955
57.9%
|
973
59%
|
1928
58.5%
|
| Lumpectomy |
283
17.2%
|
276
16.7%
|
559
16.9%
|
| Quadrantectomy/Segmental |
411
24.9%
|
400
24.3%
|
811
24.6%
|
| Primary Tumor (Number) [Number] | |||
| pT1: Tumor < = 2cm |
692
42%
|
668
40.5%
|
1360
41.2%
|
| pT2: Tumor in [ 2 - 5 ] |
824
50%
|
844
51.2%
|
1668
50.6%
|
| pT3: Tumor > 5cm |
131
7.9%
|
135
8.2%
|
266
8.1%
|
| pT4: Tumor with extension to chest wall/skin |
1
0.1%
|
2
0.1%
|
3
0.1%
|
| pTis: Carcinoma in situ |
1
0.1%
|
0
0%
|
1
0%
|
Outcome Measures
| Title | Local, Regional or Metastatic Relapse, or Second Primary Cancer, or Death From Any Cause (Disease-Free Survival) |
|---|---|
| Description | The primary event is the local, regional or metastatic relapse or the date of second primary cancer or death from any cause (whichever occurs first). The primary efficacy analysis is performed on the time from randomization to this primary event. The Measured Values table below presents the numbers of patients with the event at the end of the study period. |
| Time Frame | Median follow-up 65 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The primary efficacy analysis was performed on the Intent-to-Treat (ITT) population. Although the original Outcome Measure was intended to be presented as median disease free survival time, median time-to-event was not reached in any group; therefore, number of participants with relapse was presented. |
| Arm/Group Title | Doxorubicin + Cyclophosphamide Followed by Docetaxel (AC -> T) | Docetaxel + Doxorubicin and Cyclophosphamide (TAC) |
|---|---|---|
| Arm/Group Description | AC x 4: Doxorubicin 60 mg/m² as an IV bolus in combination with cyclophosphamide 600 mg/m² as IV followed by docetaxel 100 mg/m² as 1 hour IV infusion on day 1 every 3 weeks for 4 cycles. | TAC x 6 : Docetaxel 75 mg/m² as 1 hour IV infusion on day 1 every 3 weeks in combination with doxorubicin 50 mg/m² as an IV bolus and cyclophosphamide 500 mg/m2 as IV on day 1 every 3 weeks. Sequence of administration is as follows: doxorubicin followed by cyclophosphamide followed by docetaxel. |
| Measure Participants | 1649 | 1649 |
| Number [Participants] |
356
21.6%
|
352
21.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Doxorubicin + Cyclophosphamide Followed by Docetaxel (AC -> T), Docetaxel + Doxorubicin and Cyclophosphamide (TAC) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.978 |
| Comments | Cumulative incidence functions in each treatment group were calculated using non-parametric Kaplan-Meier estimates. | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.00 | |
| Confidence Interval |
() 95% 0.86 to 1.16 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Death From Any Cause (Overall Survival) |
|---|---|
| Description | The considered event is death from any cause. The analysis is performed on the time from randomization to this event. The Measured Values table below presents the numbers of patients with the event at the end of the study period. |
| Time Frame | Median follow-up of 65 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis was performed on the Intent-to-Treat (ITT) population. Although the original Outcome Measure was intended to be presented as median survival time, median time-to-event was not reached in any group; therefore, number of participants who died was presented. |
| Arm/Group Title | Doxorubicin + Cyclophosphamide Followed by Docetaxel (AC -> T) | Docetaxel + Doxorubicin and Cyclophosphamide (TAC) |
|---|---|---|
| Arm/Group Description | AC x 4: Doxorubicin 60 mg/m² as an IV bolus in combination with cyclophosphamide 600 mg/m² as IV followed by docetaxel 100 mg/m² as 1 hour IV infusion on day 1 every 3 weeks for 4 cycles. | TAC x 6 : Docetaxel 75 mg/m² as 1 hour IV infusion on day 1 every 3 weeks in combination with doxorubicin 50 mg/m² as an IV bolus and cyclophosphamide 500 mg/m2 as IV on day 1 every 3 weeks. Sequence of administration is as follows: doxorubicin followed by cyclophosphamide followed by docetaxel. |
| Measure Participants | 1649 | 1649 |
| Number [Participants] |
187
11.3%
|
202
12.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Doxorubicin + Cyclophosphamide Followed by Docetaxel (AC -> T), Docetaxel + Doxorubicin and Cyclophosphamide (TAC) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.371 |
| Comments | Cumulative incidences calculated in each group using non-parametric Kaplan-Meier estimates. | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.91 | |
| Confidence Interval |
() 95% 0.75 to 1.11 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | The number of patients at risk corresponds to the patients who received at least one dose of treatment | |||
| Arm/Group Title | Doxorubicin + Cyclophosphamide Followed by Docetaxel (AC -> T) | Docetaxel + Doxorubicin and Cyclophosphamide (TAC) | ||
| Arm/Group Description | AC x 4: Doxorubicin 60 mg/m² as an IV bolus in combination with cyclophosphamide 600 mg/m² as IV followed by docetaxel 100 mg/m² as 1 hour IV infusion on day 1 every 3 weeks for 4 cycles. | TAC x 6 : Docetaxel 75 mg/m² as 1 hour IV infusion on day 1 every 3 weeks in combination with doxorubicin 50 mg/m² as an IV bolus and cyclophosphamide 500 mg/m2 as IV on day 1 every 3 weeks. Sequence of administration is as follows: doxorubicin followed by cyclophosphamide followed by docetaxel. | ||
All Cause Mortality |
||||
| Doxorubicin + Cyclophosphamide Followed by Docetaxel (AC -> T) | Docetaxel + Doxorubicin and Cyclophosphamide (TAC) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Doxorubicin + Cyclophosphamide Followed by Docetaxel (AC -> T) | Docetaxel + Doxorubicin and Cyclophosphamide (TAC) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 331/1634 (20.3%) | 520/1635 (31.8%) | ||
| Blood and lymphatic system disorders | ||||
| Anemia | 3/1634 (0.2%) | 5/1635 (0.3%) | ||
| Coagulation disorders | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Hemorrhage Vaginal | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Leukopenia | 18/1634 (1.1%) | 56/1635 (3.4%) | ||
| Lymphadenopathy | 0/1634 (0%) | 1/1635 (0.1%) | ||
| Lymphedema | 0/1634 (0%) | 2/1635 (0.1%) | ||
| Pancytopenia | 0/1634 (0%) | 1/1635 (0.1%) | ||
| Thrombocytopenia | 0/1634 (0%) | 1/1635 (0.1%) | ||
| Cardiac disorders | ||||
| Arrhythmia | 3/1634 (0.2%) | 3/1635 (0.2%) | ||
| Arrhythmia Ventricular | 0/1634 (0%) | 1/1635 (0.1%) | ||
| Cardiomyopathy | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Effusion Pericardial | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Fibrillation Ventricular | 0/1634 (0%) | 1/1635 (0.1%) | ||
| Heart Arrest | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Heart Failure Left | 3/1634 (0.2%) | 0/1635 (0%) | ||
| Hypotension | 4/1634 (0.2%) | 3/1635 (0.2%) | ||
| Ischemia myocardial | 0/1634 (0%) | 2/1635 (0.1%) | ||
| Syncope | 8/1634 (0.5%) | 5/1635 (0.3%) | ||
| Tachycardia | 4/1634 (0.2%) | 1/1635 (0.1%) | ||
| Ear and labyrinth disorders | ||||
| Deaf | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Tinnitus | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Endocrine disorders | ||||
| Hyperthyroidism | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Eye disorders | ||||
| Hemorrhage Retinal | 0/1634 (0%) | 1/1635 (0.1%) | ||
| Papilledema | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Gastrointestinal disorders | ||||
| Anorexia | 2/1634 (0.1%) | 0/1635 (0%) | ||
| Colitis | 2/1634 (0.1%) | 5/1635 (0.3%) | ||
| Constipation | 1/1634 (0.1%) | 8/1635 (0.5%) | ||
| Diarrhea | 13/1634 (0.8%) | 13/1635 (0.8%) | ||
| Dyspepsia | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Dysphagia | 1/1634 (0.1%) | 3/1635 (0.2%) | ||
| Enterocolitis | 0/1634 (0%) | 1/1635 (0.1%) | ||
| Gastritis | 1/1634 (0.1%) | 2/1635 (0.1%) | ||
| Gastro-intestinal Disorder | 0/1634 (0%) | 1/1635 (0.1%) | ||
| Gastroenteritis | 0/1634 (0%) | 2/1635 (0.1%) | ||
| Hemorrhage Rectal | 2/1634 (0.1%) | 1/1635 (0.1%) | ||
| Ileus | 1/1634 (0.1%) | 1/1635 (0.1%) | ||
| Melena | 0/1634 (0%) | 1/1635 (0.1%) | ||
| Nausea | 14/1634 (0.9%) | 19/1635 (1.2%) | ||
| Proctitis | 1/1634 (0.1%) | 1/1635 (0.1%) | ||
| Stomatitis | 8/1634 (0.5%) | 9/1635 (0.6%) | ||
| Ulcer Stomach | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Vomiting | 16/1634 (1%) | 28/1635 (1.7%) | ||
| General disorders | ||||
| Abdominal Syndrom Acute | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Allergic Reaction | 7/1634 (0.4%) | 5/1635 (0.3%) | ||
| Asthenia | 5/1634 (0.3%) | 5/1635 (0.3%) | ||
| Cellulitis | 6/1634 (0.4%) | 1/1635 (0.1%) | ||
| Fever (including serious febrile neutropenia) | 122/1634 (7.5%) | 293/1635 (17.9%) | ||
| Headache | 1/1634 (0.1%) | 1/1635 (0.1%) | ||
| Hydrocephalus | 0/1634 (0%) | 1/1635 (0.1%) | ||
| Mucous Membrane Disorder | 0/1634 (0%) | 1/1635 (0.1%) | ||
| Pain | 3/1634 (0.2%) | 1/1635 (0.1%) | ||
| Pain Abdominal | 1/1634 (0.1%) | 3/1635 (0.2%) | ||
| Pain Biliary | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Pain Chest | 3/1634 (0.2%) | 3/1635 (0.2%) | ||
| Peritonitis | 0/1634 (0%) | 1/1635 (0.1%) | ||
| Weight Increase | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Hepatobiliary disorders | ||||
| Cholelithiasis | 4/1634 (0.2%) | 0/1635 (0%) | ||
| Liver Failure | 1/1634 (0.1%) | 0/1635 (0%) | ||
| SGOT Increase | 2/1634 (0.1%) | 0/1635 (0%) | ||
| SGPT Increase | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Infections and infestations | ||||
| Infection (including neutropenic infection) | 86/1634 (5.3%) | 143/1635 (8.7%) | ||
| Injury, poisoning and procedural complications | ||||
| Injury Accident | 3/1634 (0.2%) | 0/1635 (0%) | ||
| Overdose | 0/1634 (0%) | 1/1635 (0.1%) | ||
| Metabolism and nutrition disorders | ||||
| Dehydration | 8/1634 (0.5%) | 6/1635 (0.4%) | ||
| Diabetes Mellitus | 1/1634 (0.1%) | 2/1635 (0.1%) | ||
| Edema | 0/1634 (0%) | 1/1635 (0.1%) | ||
| Edema Peripheral | 5/1634 (0.3%) | 1/1635 (0.1%) | ||
| Hyperglycemia | 2/1634 (0.1%) | 1/1635 (0.1%) | ||
| Hypokalemia | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 3/1634 (0.2%) | 1/1635 (0.1%) | ||
| Arthrosis | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Myalgia | 4/1634 (0.2%) | 3/1635 (0.2%) | ||
| Myopathy | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Osteoporosis | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Cyst | 0/1634 (0%) | 1/1635 (0.1%) | ||
| Neoplasm | 0/1634 (0%) | 1/1635 (0.1%) | ||
| Neoplasm Uterine | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Nodule skin | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Nervous system disorders | ||||
| Convulsion | 1/1634 (0.1%) | 2/1635 (0.1%) | ||
| Delusions | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Depression | 2/1634 (0.1%) | 1/1635 (0.1%) | ||
| Dizziness | 0/1634 (0%) | 1/1635 (0.1%) | ||
| Emotional Lability | 1/1634 (0.1%) | 1/1635 (0.1%) | ||
| Encephalopathy | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Neuralgia | 0/1634 (0%) | 1/1635 (0.1%) | ||
| Neuropathy | 6/1634 (0.4%) | 3/1635 (0.2%) | ||
| Paralysis Vocal Cord | 0/1634 (0%) | 1/1635 (0.1%) | ||
| Vertigo | 0/1634 (0%) | 1/1635 (0.1%) | ||
| Pregnancy, puerperium and perinatal conditions | ||||
| Pregnancy Unintended | 0/1634 (0%) | 2/1635 (0.1%) | ||
| Psychiatric disorders | ||||
| Psychosis | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Renal and urinary disorders | ||||
| Creatinine increase | 0/1634 (0%) | 2/1635 (0.1%) | ||
| Cystitis | 0/1634 (0%) | 2/1635 (0.1%) | ||
| Kidney Failure | 2/1634 (0.1%) | 1/1635 (0.1%) | ||
| Mastitis | 0/1634 (0%) | 1/1635 (0.1%) | ||
| Urinary Retention | 0/1634 (0%) | 1/1635 (0.1%) | ||
| Urinary Tract Disorder | 0/1634 (0%) | 1/1635 (0.1%) | ||
| Reproductive system and breast disorders | ||||
| Menstrual Disorder | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Metrorrhagia | 0/1634 (0%) | 1/1635 (0.1%) | ||
| Uterine Fibroid Enlargement | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Vaginitis | 0/1634 (0%) | 1/1635 (0.1%) | ||
| Vulvovaginitis | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnea | 5/1634 (0.3%) | 3/1635 (0.2%) | ||
| Effusion Pleural | 0/1634 (0%) | 1/1635 (0.1%) | ||
| Fibrosis lung | 0/1634 (0%) | 1/1635 (0.1%) | ||
| Lung Disorder | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Pharyngitis | 0/1634 (0%) | 2/1635 (0.1%) | ||
| Pneumonia | 0/1634 (0%) | 1/1635 (0.1%) | ||
| Pneumonia Interstitial | 2/1634 (0.1%) | 1/1635 (0.1%) | ||
| Pneumothorax | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Rhinitis | 1/1634 (0.1%) | 1/1635 (0.1%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 3/1634 (0.2%) | 2/1635 (0.1%) | ||
| Derm Exfoliating | 8/1634 (0.5%) | 1/1635 (0.1%) | ||
| Erythema Multiform | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Herpes Zoster | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Injection site reaction | 1/1634 (0.1%) | 1/1635 (0.1%) | ||
| Nail Disorder | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Rash Maculopapular | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Vascular disorders | ||||
| Arteriosclerosis | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Cerebrovascular Accident | 2/1634 (0.1%) | 1/1635 (0.1%) | ||
| Hemorrhage Intracranial | 1/1634 (0.1%) | 0/1635 (0%) | ||
| Thrombophlebitis Deep | 14/1634 (0.9%) | 14/1635 (0.9%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Doxorubicin + Cyclophosphamide Followed by Docetaxel (AC -> T) | Docetaxel + Doxorubicin and Cyclophosphamide (TAC) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1634/1634 (100%) | 1629/1635 (99.6%) | ||
| Blood and lymphatic system disorders | ||||
| Anemia | 461/1634 (28.2%) | 658/1635 (40.2%) | ||
| Epistaxis | 123/1634 (7.5%) | 72/1635 (4.4%) | ||
| Leucopenia | 59/1634 (3.6%) | 88/1635 (5.4%) | ||
| Lymphedema | 101/1634 (6.2%) | 109/1635 (6.7%) | ||
| Neutropenia | 1133/1634 (69.3%) | 1049/1635 (64.2%) | ||
| Thrombocytopenia | 52/1634 (3.2%) | 109/1635 (6.7%) | ||
| Cardiac disorders | ||||
| Palpitations | 82/1634 (5%) | 84/1635 (5.1%) | ||
| Eye disorders | ||||
| Conjunctivitis | 176/1634 (10.8%) | 131/1635 (8%) | ||
| Dry eye | 87/1634 (5.3%) | 65/1635 (4%) | ||
| Lacrimation disorder | 357/1634 (21.8%) | 212/1635 (13%) | ||
| Gastrointestinal disorders | ||||
| Anorexia | 370/1634 (22.6%) | 376/1635 (23%) | ||
| Constipation | 599/1634 (36.7%) | 555/1635 (33.9%) | ||
| Diarrhea | 644/1634 (39.4%) | 606/1635 (37.1%) | ||
| Dyspepsia | 339/1634 (20.7%) | 387/1635 (23.7%) | ||
| Dysphagia | 83/1634 (5.1%) | 65/1635 (4%) | ||
| Nausea | 1435/1634 (87.8%) | 1334/1635 (81.6%) | ||
| Proctitis | 82/1634 (5%) | 100/1635 (6.1%) | ||
| Stomatitis | 1035/1634 (63.3%) | 1026/1635 (62.8%) | ||
| Taste pervers | 480/1634 (29.4%) | 426/1635 (26.1%) | ||
| Vomiting | 907/1634 (55.5%) | 742/1635 (45.4%) | ||
| General disorders | ||||
| Allergic reaction | 172/1634 (10.5%) | 190/1635 (11.6%) | ||
| Fever (including febrile neutropenia) | 289/1634 (17.7%) | 467/1635 (28.6%) | ||
| Headache | 433/1634 (26.5%) | 370/1635 (22.6%) | ||
| Injection site reaction | 124/1634 (7.6%) | 92/1635 (5.6%) | ||
| Pain | 275/1634 (16.8%) | 235/1635 (14.4%) | ||
| Pain abdominal | 256/1634 (15.7%) | 271/1635 (16.6%) | ||
| Pain back | 123/1634 (7.5%) | 121/1635 (7.4%) | ||
| Pain bone | 230/1634 (14.1%) | 204/1635 (12.5%) | ||
| Pain chest | 93/1634 (5.7%) | 76/1635 (4.6%) | ||
| Weight decrease | 116/1634 (7.1%) | 140/1635 (8.6%) | ||
| Weight increase | 370/1634 (22.6%) | 240/1635 (14.7%) | ||
| Infections and infestations | ||||
| Infection (including neutropenic infection) | 573/1634 (35.1%) | 457/1635 (28%) | ||
| Metabolism and nutrition disorders | ||||
| Edema peripheral | 488/1634 (29.9%) | 417/1635 (25.5%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 602/1634 (36.8%) | 382/1635 (23.4%) | ||
| Asthenia | 1328/1634 (81.3%) | 1310/1635 (80.1%) | ||
| Myalgia | 834/1634 (51%) | 587/1635 (35.9%) | ||
| Nervous system disorders | ||||
| Depression | 160/1634 (9.8%) | 132/1635 (8.1%) | ||
| Dizziness | 149/1634 (9.1%) | 169/1635 (10.3%) | ||
| Dry mouth | 149/1634 (9.1%) | 80/1635 (4.9%) | ||
| Emotion labil | 168/1634 (10.3%) | 111/1635 (6.8%) | ||
| Insomnia | 334/1634 (20.4%) | 277/1635 (16.9%) | ||
| Neuropathy | 723/1634 (44.2%) | 482/1635 (29.5%) | ||
| Vasodilatation | 388/1634 (23.7%) | 437/1635 (26.7%) | ||
| Reproductive system and breast disorders | ||||
| Menses disorder | 489/1634 (29.9%) | 501/1635 (30.6%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 211/1634 (12.9%) | 222/1635 (13.6%) | ||
| Dyspnea | 319/1634 (19.5%) | 287/1635 (17.6%) | ||
| Pharyngitis | 88/1634 (5.4%) | 69/1635 (4.2%) | ||
| Rhinitis | 268/1634 (16.4%) | 198/1635 (12.1%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 1601/1634 (98%) | 1587/1635 (97.1%) | ||
| Derm exfoliating | 143/1634 (8.8%) | 36/1635 (2.2%) | ||
| Nail disorder | 729/1634 (44.6%) | 363/1635 (22.2%) | ||
| Rash maculopapular | 402/1634 (24.6%) | 314/1635 (19.2%) | ||
| Skin dry | 107/1634 (6.5%) | 85/1635 (5.2%) | ||
| Sweating | 77/1634 (4.7%) | 93/1635 (5.7%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Results Point of Contact
| Name/Title | Medical Affairs study director |
|---|---|
| Organization | sanofi-aventis |
| Phone | |
| publicregistryGMA@sanofi-aventis.com |
- TAX_GMA_301
- BCIRG 005