Docetaxel, Doxorubicin (A), Cyclophosphamide (C) (TAC) vs 5-Fluorouracil, A, C (5FAC) Breast Cancer Adjuvant Treatment

Sponsor
Spanish Breast Cancer Research Group (Other)
Overall Status
Completed
CT.gov ID
NCT00121992
Collaborator
Sanofi (Industry)
1,060
1
2
164.2
6.5

Study Details

Study Description

Brief Summary

This is a prospective, non-blinded randomized phase III trial. Patients will be post-surgically stratified at inclusion first according to the participating institution, then according to menopausal status and will be randomly assigned to receive either:

  • TAC: Docetaxel 75 mg/m2 as a 1 hour intravenous (i.v.) infusion on day 1 every 3 weeks (q3w) in combination with doxorubicin 50 mg/m2 as an i.v. bolus and cyclophosphamide 500 mg/m2 as an i.v. bolus on day 1 every 3 weeks.

  • FAC: 5-fluorouracil 500 mg/m2 as an i.v. bolus on day 1 every 3 weeks in combination with doxorubicin 50 mg/m2 as an i.v. bolus and cyclophosphamide 500 mg/m2 as an i.v. bolus on day 1 every 3 weeks.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

Primary objective:
  • To compare disease-free survival (DFS) after treatment with docetaxel in combination with doxorubicin and cyclophosphamide (TAC) to 5-Fluorouracil in combination with doxorubicin and cyclophosphamide (FAC) as adjuvant treatment of high risk operable breast cancer patients with negative axillary lymph nodes.
Secondary objectives:
  • To compare overall survival (OS) between the 2 above mentioned arms.

  • To compare toxicity and quality of life between the 2 above mentioned arms.

  • To evaluate pathologic markers for predicting efficacy (hormonal receptors and human epidermal growth factor receptor 2 (HER2) protein expression).

Study Design

Study Type:
Interventional
Actual Enrollment :
1060 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase III Randomized Comparing Docetaxel, Doxorubicin and Cyclophosphamide (TAC) vs 5-Fluorouracil, Doxorubicin and Cyclophosphamide (FAC) as Adjuvant Treatment of High Risk Operable Breast Cancer Patients With Negative Axillary Lymph Nodes
Actual Study Start Date :
Jul 1, 1999
Actual Primary Completion Date :
Dec 2, 2010
Actual Study Completion Date :
Mar 6, 2013

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Arm A: FAC

FAC (5-fluorouracil, doxorubicin, cyclophosphamide): 5-fluorouracil 500 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv

Drug: 5-fluorouracil
Other Names:
  • Adrucil
  • Drug: Doxorubicin
    Other Names:
  • adriamycin
  • Drug: Cyclophosphamide
    Other Names:
  • cytoxan
  • Experimental: Arm B: TAC

    TAC (docetaxel, doxorubicin, cyclophosphamide): Docetaxel 75 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv

    Drug: Docetaxel
    Other Names:
  • Taxotere
  • Drug: Doxorubicin
    Other Names:
  • adriamycin
  • Drug: Cyclophosphamide
    Other Names:
  • cytoxan
  • Outcome Measures

    Primary Outcome Measures

    1. Disease-free Survival (DFS) Events [10 years]

      DFS is calculated from the date of randomization until the first date of recurrence local, regional or distant, second primary tumor or death.

    Secondary Outcome Measures

    1. Overall Survival (OS) [10 years]

      OS was determined from the date of randomization until the date of death for any reason. OS is calculated from the date of randomization up to the first date of death by any cause.

    2. The Number of Participants Who Experienced Adverse Events (AE) [Through study treatment, and average of 4 months]

      Safety was assessed by standard clinical and laboratory tests (haematology, serum chemistry). AE grade were defined by the NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) version 1.0.

    3. Best Score During Study for Global Health Status Scale [120 weeks]

      The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) was used. Questionnaires were self-administered to patients during the 14 days prior to randomisation baseline, at six prospective time points corresponding to chemotherapy cycles, with the time window related to each chemotherapy cycle defined as the period between the day following the first chemotherapy dose of the corresponding cycle and the day of the first dose of the following cycle, and then at 44, 68 and 120 weeks of the study. The Global Health Status Scale has been used, which is calculated with questions 29 and 30 from the EORTC QLQ-C30. From this scale, the best score is the highest score observed during study (of all the questionnaires completed by patient). In this scale, scores range from 0 to 100 and a high score represents a high level of functioning or HRQoL.

    4. Number of Disease Free Survival Events in Hormone-receptor Positive and Human Epidermal Growth Factor Receptor 2 (HER2) Positive Status Subgroup [10 year]

      Hormone-receptor status and HER2 receptor status was analysed in Paraffin-embedded tumor samples obtained at the time of surgery, and were processed centrally. Disease-Free Survival (DFS) is defined as the interval from the date of randomization to the date of local, regional or metastatic relapse or the date of second primary cancer or death from any cause whichever occurs first.

    5. Disease Free Survival in Hormonal Receptor Positive and HER2 Negative Subgroup [10 year]

      Hormone-receptor status and HER2 receptor status was analysed in Paraffin-embedded tumor samples obtained at the time of surgery, and were processed centrally. Disease-Free Survival (DFS) is defined as the interval from the date of randomization to the date of local, regional or metastatic relapse or the date of second primary cancer or death from any cause whichever occurs first.

    6. Disease Free Survival in Hormonal Receptor Negative and HER2 Positive Subgroup [10 year]

      Hormone-receptor status and HER2 receptor status was analysed in Paraffin-embedded tumor samples obtained at the time of surgery, and were processed centrally.

    7. Disease Free Survival in Hormonal Receptor Negative and HER2 Negative Subgroup [10 year]

      Hormone-receptor status and HER2 receptor status was analysed in Paraffin-embedded tumor samples obtained at the time of surgery, and were processed centrally. Disease-Free Survival (DFS) is defined as the interval from the date of randomization to the date of local, regional or metastatic relapse or the date of second primary cancer or death from any cause whichever occurs first.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Written informed consent

    • Operable breast cancer patients (T1-T3) with negative axillary lymph nodes (10 axillary nodes dissection) and high risk criteria according to St. Gallen consensus criteria.

    • Histologically proven breast cancer. Interval between surgery and registration is less than 60 days.

    • Definitive surgical treatment must be either mastectomy, or breast conservative surgery. Margins of resected specimen from surgery must be histologically free of invasive adenocarcinoma and ductal carcinoma in-situ (DCIS). Lobular carcinoma in-situ is not considered as positive margin.

    • Patients without proven metastatic disease.

    • Estrogen and progesterone receptors performed on the primary tumour prior to randomization.

    • Age between 18 years and 70 years.

    • Karnofsky performance status index > 80 %.

    • Adequate hepatic, renal and heart functions.

    • Adequate hematology levels.

    • Negative pregnancy test

    Exclusion Criteria:
    • Prior systemic anticancer therapy for breast cancer (immunotherapy, hormonotherapy, 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 .

    • Any T4 or N1-3 or M1 breast cancer.

    • Pre-existing motor or sensory neurotoxicity of a severity grade 2 by NCI criteria.

    • Other serious illness or medical condition

    • Past or current history of neoplasm other than breast carcinoma.

    • 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

    • 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.

    • Male patients.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Spanish Breast Cancer Research Group San Sebastián de los Reyes Madrid Spain 28700

    Sponsors and Collaborators

    • Spanish Breast Cancer Research Group
    • Sanofi

    Investigators

    • Study Director: Study Director, Hospital Universitario San Carlos

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Spanish Breast Cancer Research Group
    ClinicalTrials.gov Identifier:
    NCT00121992
    Other Study ID Numbers:
    • GEICAM 9805
    • TAX.ES1.301
    First Posted:
    Jul 21, 2005
    Last Update Posted:
    Dec 4, 2020
    Last Verified:
    Nov 1, 2020
    Keywords provided by Spanish Breast Cancer Research Group
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details For the different subsets ("Hormone-receptor Positive and HER2 PositiveStatus Subjects", "Hormonal Receptor Positive and HER2 Negative Subjects", etc.), were assessed by central determination, and no all patients had tumor sample available.
    Pre-assignment Detail
    Arm/Group Title Arm A: FAC Arm B: TAC
    Arm/Group Description FAC (5-fluorouracil, doxorubicin, cyclophosphamide): 5-fluorouracil 500 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv 5-fluorouracil Doxorubicin Cyclophosphamide TAC (docetaxel, doxorubicin, cyclophosphamide): Docetaxel 75 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv Docetaxel Doxorubicin Cyclophosphamide
    Period Title: Overall Study
    STARTED 521 539
    Hormone-receptor Positive and HER2 Positive Status Subjects 28 30
    Hormone-receptor Negative and HER2 Positive Status Subjects 24 22
    Hormone-receptor Positive and HER2 Negative Status Subjects 209 220
    Hormone-receptor Negative and HER2 Negative Status Subjects 92 103
    COMPLETED 519 528
    NOT COMPLETED 2 11

    Baseline Characteristics

    Arm/Group Title Arm A: FAC Arm B: TAC Total
    Arm/Group Description FAC (5-fluorouracil, doxorubicin, cyclophosphamide): 5-fluorouracil 500 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv 5-fluorouracil Doxorubicin Cyclophosphamide TAC (docetaxel, doxorubicin, cyclophosphamide): Docetaxel 75 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv Docetaxel Doxorubicin Cyclophosphamide Total of all reporting groups
    Overall Participants 521 539 1060
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    49
    50
    49
    Sex: Female, Male (Count of Participants)
    Female
    521
    100%
    539
    100%
    1060
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    Spain
    475
    91.2%
    487
    90.4%
    962
    90.8%
    Germany
    26
    5%
    30
    5.6%
    56
    5.3%
    Poland
    20
    3.8%
    22
    4.1%
    42
    4%
    Tumor size (Count of Participants)
    ≤2 cm
    249
    47.8%
    285
    52.9%
    534
    50.4%
    >2 to 5 cm
    258
    49.5%
    241
    44.7%
    499
    47.1%
    >5 cm
    13
    2.5%
    13
    2.4%
    26
    2.5%
    Unknown
    1
    0.2%
    0
    0%
    1
    0.1%
    Tumor grade (Count of Participants)
    Grade 1
    34
    6.5%
    38
    7.1%
    72
    6.8%
    Grade 2
    230
    44.1%
    216
    40.1%
    446
    42.1%
    Grade 3
    231
    44.3%
    259
    48.1%
    490
    46.2%
    Unknown
    26
    5%
    26
    4.8%
    52
    4.9%
    Menopausal status (Count of Participants)
    Premenopausal
    272
    52.2%
    285
    52.9%
    557
    52.5%
    Postmenopausal
    249
    47.8%
    254
    47.1%
    503
    47.5%
    Hormone-receptor status (Count of Participants)
    Positive
    349
    67%
    344
    63.8%
    693
    65.4%
    Negative
    170
    32.6%
    192
    35.6%
    362
    34.2%
    Unknown
    2
    0.4%
    3
    0.6%
    5
    0.5%
    Surgery (Count of Participants)
    Breast-conserving surgery: With radiation
    247
    47.4%
    287
    53.2%
    534
    50.4%
    Breast-conserving surgery: Without radiation
    24
    4.6%
    24
    4.5%
    48
    4.5%
    Mastectomy: With radiation
    20
    3.8%
    22
    4.1%
    42
    4%
    Mastectomy: Without radiation
    230
    44.1%
    206
    38.2%
    436
    41.1%

    Outcome Measures

    1. Primary Outcome
    Title Disease-free Survival (DFS) Events
    Description DFS is calculated from the date of randomization until the first date of recurrence local, regional or distant, second primary tumor or death.
    Time Frame 10 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm A: FAC Arm B: TAC
    Arm/Group Description FAC (5-fluorouracil, doxorubicin, cyclophosphamide): 5-fluorouracil 500 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv 5-fluorouracil Doxorubicin Cyclophosphamide TAC (docetaxel, doxorubicin, cyclophosphamide): Docetaxel 75 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv Docetaxel Doxorubicin Cyclophosphamide
    Measure Participants 521 539
    Number [events]
    127
    112
    2. Secondary Outcome
    Title Overall Survival (OS)
    Description OS was determined from the date of randomization until the date of death for any reason. OS is calculated from the date of randomization up to the first date of death by any cause.
    Time Frame 10 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm A: FAC Arm B: TAC
    Arm/Group Description FAC (5-fluorouracil, doxorubicin, cyclophosphamide): 5-fluorouracil 500 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv 5-fluorouracil Doxorubicin Cyclophosphamide TAC (docetaxel, doxorubicin, cyclophosphamide): Docetaxel 75 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv Docetaxel Doxorubicin Cyclophosphamide
    Measure Participants 521 539
    Number [Participants with mortality event]
    57
    10.9%
    53
    9.8%
    3. Secondary Outcome
    Title The Number of Participants Who Experienced Adverse Events (AE)
    Description Safety was assessed by standard clinical and laboratory tests (haematology, serum chemistry). AE grade were defined by the NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) version 1.0.
    Time Frame Through study treatment, and average of 4 months

    Outcome Measure Data

    Analysis Population Description
    The safety analysis was conducted on all patients who started at least one infusion of the study treatment (Arm A 519, and Arm B 532).
    Arm/Group Title Arm A: FAC Arm B: TAC
    Arm/Group Description FAC (5-fluorouracil, doxorubicin, cyclophosphamide): 5-fluorouracil 500 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv 5-fluorouracil Doxorubicin Cyclophosphamide TAC (docetaxel, doxorubicin, cyclophosphamide): Docetaxel 75 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv Docetaxel Doxorubicin Cyclophosphamide
    Measure Participants 519 532
    Number patients with One AE
    519
    99.6%
    532
    98.7%
    One G3-4 or severe treatment-emergent AE
    88
    16.9%
    151
    28%
    One serious treatment-emergent AE
    22
    4.2%
    119
    22.1%
    One serious G3-4 treatment-emergent AE
    10
    1.9%
    55
    10.2%
    Number of patients discontinued due to AE
    4
    0.8%
    25
    4.6%
    Number patients death due to AE
    0
    0%
    1
    0.2%
    4. Secondary Outcome
    Title Best Score During Study for Global Health Status Scale
    Description The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) was used. Questionnaires were self-administered to patients during the 14 days prior to randomisation baseline, at six prospective time points corresponding to chemotherapy cycles, with the time window related to each chemotherapy cycle defined as the period between the day following the first chemotherapy dose of the corresponding cycle and the day of the first dose of the following cycle, and then at 44, 68 and 120 weeks of the study. The Global Health Status Scale has been used, which is calculated with questions 29 and 30 from the EORTC QLQ-C30. From this scale, the best score is the highest score observed during study (of all the questionnaires completed by patient). In this scale, scores range from 0 to 100 and a high score represents a high level of functioning or HRQoL.
    Time Frame 120 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm A: FAC Arm B: TAC
    Arm/Group Description FAC (5-fluorouracil, doxorubicin, cyclophosphamide): 5-fluorouracil 500 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv 5-fluorouracil Doxorubicin Cyclophosphamide TAC (docetaxel, doxorubicin, cyclophosphamide): Docetaxel 75 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv Docetaxel Doxorubicin Cyclophosphamide
    Measure Participants 519 532
    Mean (Standard Deviation) [score on a scale]
    79.30
    (17.64)
    77.78
    (18.87)
    5. Secondary Outcome
    Title Number of Disease Free Survival Events in Hormone-receptor Positive and Human Epidermal Growth Factor Receptor 2 (HER2) Positive Status Subgroup
    Description Hormone-receptor status and HER2 receptor status was analysed in Paraffin-embedded tumor samples obtained at the time of surgery, and were processed centrally. Disease-Free Survival (DFS) is defined as the interval from the date of randomization to the date of local, regional or metastatic relapse or the date of second primary cancer or death from any cause whichever occurs first.
    Time Frame 10 year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm A: FAC Arm B: TAC
    Arm/Group Description FAC (5-fluorouracil, doxorubicin, cyclophosphamide): 5-fluorouracil 500 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv 5-fluorouracil Doxorubicin Cyclophosphamide TAC (docetaxel, doxorubicin, cyclophosphamide): Docetaxel 75 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv Docetaxel Doxorubicin Cyclophosphamide
    Measure Participants 28 30
    Number [events]
    6
    6
    6. Secondary Outcome
    Title Disease Free Survival in Hormonal Receptor Positive and HER2 Negative Subgroup
    Description Hormone-receptor status and HER2 receptor status was analysed in Paraffin-embedded tumor samples obtained at the time of surgery, and were processed centrally. Disease-Free Survival (DFS) is defined as the interval from the date of randomization to the date of local, regional or metastatic relapse or the date of second primary cancer or death from any cause whichever occurs first.
    Time Frame 10 year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm A: FAC Arm B: TAC
    Arm/Group Description FAC (5-fluorouracil, doxorubicin, cyclophosphamide): 5-fluorouracil 500 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv 5-fluorouracil Doxorubicin Cyclophosphamide TAC (docetaxel, doxorubicin, cyclophosphamide): Docetaxel 75 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv Docetaxel Doxorubicin Cyclophosphamide
    Measure Participants 209 220
    Number [events]
    50
    37
    7. Secondary Outcome
    Title Disease Free Survival in Hormonal Receptor Negative and HER2 Positive Subgroup
    Description Hormone-receptor status and HER2 receptor status was analysed in Paraffin-embedded tumor samples obtained at the time of surgery, and were processed centrally.
    Time Frame 10 year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm A: FAC Arm B: TAC
    Arm/Group Description FAC (5-fluorouracil, doxorubicin, cyclophosphamide): 5-fluorouracil 500 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv 5-fluorouracil Doxorubicin Cyclophosphamide TAC (docetaxel, doxorubicin, cyclophosphamide): Docetaxel 75 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv Docetaxel Doxorubicin Cyclophosphamide
    Measure Participants 24 22
    Number [events]
    6
    5
    8. Secondary Outcome
    Title Disease Free Survival in Hormonal Receptor Negative and HER2 Negative Subgroup
    Description Hormone-receptor status and HER2 receptor status was analysed in Paraffin-embedded tumor samples obtained at the time of surgery, and were processed centrally. Disease-Free Survival (DFS) is defined as the interval from the date of randomization to the date of local, regional or metastatic relapse or the date of second primary cancer or death from any cause whichever occurs first.
    Time Frame 10 year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm A: FAC Arm B: TAC
    Arm/Group Description FAC (5-fluorouracil, doxorubicin, cyclophosphamide): 5-fluorouracil 500 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv 5-fluorouracil Doxorubicin Cyclophosphamide TAC (docetaxel, doxorubicin, cyclophosphamide): Docetaxel 75 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv Docetaxel Doxorubicin Cyclophosphamide
    Measure Participants 92 103
    Number [events]
    29
    28

    Adverse Events

    Time Frame Through study treatment, an average of 18 weeks
    Adverse Event Reporting Description The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
    Arm/Group Title Arm A: FAC Arm B: TAC
    Arm/Group Description FAC (5-fluorouracil, doxorubicin, cyclophosphamide): 5-fluorouracil 500 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv 5-fluorouracil Doxorubicin Cyclophosphamide TAC (docetaxel, doxorubicin, cyclophosphamide): Docetaxel 75 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv Docetaxel Doxorubicin Cyclophosphamide
    All Cause Mortality
    Arm A: FAC Arm B: TAC
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 57/519 (11%) 53/532 (10%)
    Serious Adverse Events
    Arm A: FAC Arm B: TAC
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 21/519 (4%) 119/532 (22.4%)
    Blood and lymphatic system disorders
    Anaemia 1/519 (0.2%) 1/532 (0.2%)
    Blood bilirubin 0/519 (0%) 1/532 (0.2%)
    Leukopenia 0/519 (0%) 1/532 (0.2%)
    Neutropenia 1/519 (0.2%) 5/532 (0.9%)
    Cardiac disorders
    Arrhythmia 0/519 (0%) 1/532 (0.2%)
    Carotid artery thrombosis 1/519 (0.2%) 0/532 (0%)
    Ear and labyrinth disorders
    Ear infection 0/519 (0%) 1/532 (0.2%)
    Eye disorders
    Conjunctivitis 0/519 (0%) 1/532 (0.2%)
    Gastrointestinal disorders
    Abdominal pain 1/519 (0.2%) 1/532 (0.2%)
    Anal fissure 0/519 (0%) 1/532 (0.2%)
    Constipation 0/519 (0%) 1/532 (0.2%)
    Diarrhoea 1/519 (0.2%) 6/532 (1.1%)
    Dyspepsia 0/519 (0%) 1/532 (0.2%)
    Nausea 1/519 (0.2%) 4/532 (0.8%)
    General disorders
    Asthenia 0/519 (0%) 1/532 (0.2%)
    Fever in absence of infection 12/519 (2.3%) 68/532 (12.8%)
    General physical health deterioration 0/519 (0%) 1/532 (0.2%)
    Pyrexia 0/519 (0%) 2/532 (0.4%)
    Infections and infestations
    Cellulitis 0/519 (0%) 1/532 (0.2%)
    Device related infection 0/519 (0%) 1/532 (0.2%)
    Localised infection 0/519 (0%) 1/532 (0.2%)
    Postoperative wound infection 0/519 (0%) 1/532 (0.2%)
    Skin infection 0/519 (0%) 2/532 (0.4%)
    Wound infection 0/519 (0%) 1/532 (0.2%)
    Investigations
    Febrile neutropenia 0/519 (0%) 3/532 (0.6%)
    Metabolism and nutrition disorders
    Pancreatitis 0/519 (0%) 1/532 (0.2%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Disease progression 0/519 (0%) 1/532 (0.2%)
    Nervous system disorders
    Hypersensitivity 0/519 (0%) 1/532 (0.2%)
    Reproductive system and breast disorders
    Breast cyst 0/519 (0%) 1/532 (0.2%)
    Breast infection 1/519 (0.2%) 0/532 (0%)
    Breast haematoma 1/519 (0.2%) 0/532 (0%)
    Menorrhagia 0/519 (0%) 1/532 (0.2%)
    Respiratory, thoracic and mediastinal disorders
    Bronchopneumonia 0/519 (0%) 1/532 (0.2%)
    Cough 0/519 (0%) 1/532 (0.2%)
    Respiratory tract infection 0/519 (0%) 1/532 (0.2%)
    Tonsillitis 0/519 (0%) 1/532 (0.2%)
    Skin and subcutaneous tissue disorders
    Erysipelas 0/519 (0%) 1/532 (0.2%)
    Vascular disorders
    Deep vein thrombosis 1/519 (0.2%) 0/532 (0%)
    Oedema peripheral 0/519 (0%) 1/532 (0.2%)
    Thrombosis 0/519 (0%) 1/532 (0.2%)
    Other (Not Including Serious) Adverse Events
    Arm A: FAC Arm B: TAC
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 519/519 (100%) 532/532 (100%)
    Blood and lymphatic system disorders
    Neutropenia 9/519 (1.7%) 33/532 (6.2%)
    Thrombocytopenia 2/519 (0.4%) 2/532 (0.4%)
    Cardiac disorders
    Arrhythmia 6/519 (1.2%) 12/532 (2.3%)
    Cardiac failure 0/519 (0%) 1/532 (0.2%)
    Eye disorders
    Conjunctivitis 104/519 (20%) 108/532 (20.3%)
    Lacrimation increased 18/519 (3.5%) 24/532 (4.5%)
    Gastrointestinal disorders
    Nausea 387/519 (74.6%) 379/532 (71.2%)
    Stomatitis 265/519 (51.1%) 292/532 (54.9%)
    Vomiting 294/519 (56.6%) 292/532 (54.9%)
    Diarrhoea 70/519 (13.5%) 147/532 (27.6%)
    Abdominal pain upper 71/519 (13.7%) 88/532 (16.5%)
    Dyspepsia 50/519 (9.6%) 57/532 (10.7%)
    Haemorrhoids 6/519 (1.2%) 11/532 (2.1%)
    Flatulence 2/519 (0.4%) 6/532 (1.1%)
    Anal abscess 0/519 (0%) 1/532 (0.2%)
    General disorders
    Asthenia 305/519 (58.8%) 387/532 (72.7%)
    Pain 80/519 (15.4%) 118/532 (22.2%)
    Pyrexia 46/519 (8.9%) 90/532 (16.9%)
    Decreased appetite 69/519 (13.3%) 88/532 (16.5%)
    Weight increased 10/519 (1.9%) 29/532 (5.5%)
    Bone pain 1/519 (0.2%) 18/532 (3.4%)
    Back pain 6/519 (1.2%) 17/532 (3.2%)
    Fatigue 7/519 (1.3%) 4/532 (0.8%)
    Hyperhidrosis 1/519 (0.2%) 3/532 (0.6%)
    Infections and infestations
    Urinary tract infection 10/519 (1.9%) 11/532 (2.1%)
    Vaginal infection 1/519 (0.2%) 5/532 (0.9%)
    Infection 0/519 (0%) 3/532 (0.6%)
    Herpes zoster 3/519 (0.6%) 2/532 (0.4%)
    Musculoskeletal and connective tissue disorders
    Myalgia 15/519 (2.9%) 123/532 (23.1%)
    Arthralgia 30/519 (5.8%) 108/532 (20.3%)
    Nervous system disorders
    Dysgeusia 71/519 (13.7%) 85/532 (16%)
    Peripheral Sensory Neuropathy 38/519 (7.3%) 83/532 (15.6%)
    Peripheral motor neuropathy 2/519 (0.4%) 18/532 (3.4%)
    Photophobia 1/519 (0.2%) 6/532 (1.1%)
    Visual impairment 1/519 (0.2%) 3/532 (0.6%)
    Psychiatric disorders
    Insomnia 24/519 (4.6%) 27/532 (5.1%)
    Affective disorder 28/519 (5.4%) 25/532 (4.7%)
    Reproductive system and breast disorders
    Amenorrhoea 70/519 (13.5%) 121/532 (22.7%)
    Menstruation irregular 90/519 (17.3%) 103/532 (19.4%)
    Hot flush 54/519 (10.4%) 74/532 (13.9%)
    Metrorrhagia 2/519 (0.4%) 4/532 (0.8%)
    Vaginal haemorrhage 1/519 (0.2%) 3/532 (0.6%)
    Respiratory, thoracic and mediastinal disorders
    Cough 24/519 (4.6%) 26/532 (4.9%)
    Lung disorder 14/519 (2.7%) 17/532 (3.2%)
    Dyspnoea 3/519 (0.6%) 12/532 (2.3%)
    Chest pain 6/519 (1.2%) 7/532 (1.3%)
    Pleural effusion 0/519 (0%) 1/532 (0.2%)
    Pulmonary embolism 1/519 (0.2%) 0/532 (0%)
    Skin and subcutaneous tissue disorders
    Alopecia 508/519 (97.9%) 514/532 (96.6%)
    Nail disorder 77/519 (14.8%) 102/532 (19.2%)
    Skin disorder 51/519 (9.8%) 96/532 (18%)
    Erythema 5/519 (1%) 10/532 (1.9%)
    Pigmentation disorder 0/519 (0%) 2/532 (0.4%)
    Dry skin 2/519 (0.4%) 1/532 (0.2%)
    Vascular disorders
    Oedema peripheral 19/519 (3.7%) 101/532 (19%)
    Lymphoedema 3/519 (0.6%) 13/532 (2.4%)
    Varicose vein 0/519 (0%) 1/532 (0.2%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Scientific Director / Medical Lead / Project Manager
    Organization Spanish Breast Cancer Research Group
    Phone +34916592870
    Email geicam@geicam.org
    Responsible Party:
    Spanish Breast Cancer Research Group
    ClinicalTrials.gov Identifier:
    NCT00121992
    Other Study ID Numbers:
    • GEICAM 9805
    • TAX.ES1.301
    First Posted:
    Jul 21, 2005
    Last Update Posted:
    Dec 4, 2020
    Last Verified:
    Nov 1, 2020