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
Enrollment
1
Location
2
Arms
164.2
Actual Duration (Months)
6.5
Patients Per Site Per Month

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.

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

ArmIntervention/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

    SiteCityStateCountryPostal Code
    1Spanish Breast Cancer Research GroupSan Sebastián de los ReyesMadridSpain28700

    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

    Study Results

    Participant Flow

    Recruitment DetailsFor 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 TitleArm A: FACArm B: TAC
    Arm/Group DescriptionFAC (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 CyclophosphamideTAC (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
    STARTED521539
    Hormone-receptor Positive and HER2 Positive Status Subjects2830
    Hormone-receptor Negative and HER2 Positive Status Subjects2422
    Hormone-receptor Positive and HER2 Negative Status Subjects209220
    Hormone-receptor Negative and HER2 Negative Status Subjects92103
    COMPLETED519528
    NOT COMPLETED211

    Baseline Characteristics

    Arm/Group TitleArm A: FACArm B: TACTotal
    Arm/Group DescriptionFAC (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 CyclophosphamideTAC (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 CyclophosphamideTotal of all reporting groups
    Overall Participants5215391060
    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
    TitleDisease-free Survival (DFS) Events
    DescriptionDFS is calculated from the date of randomization until the first date of recurrence local, regional or distant, second primary tumor or death.
    Time Frame10 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleArm A: FACArm B: TAC
    Arm/Group DescriptionFAC (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 CyclophosphamideTAC (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 Participants521539
    Number [events]
    127
    112
    2. Secondary Outcome
    TitleOverall Survival (OS)
    DescriptionOS 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 Frame10 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleArm A: FACArm B: TAC
    Arm/Group DescriptionFAC (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 CyclophosphamideTAC (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 Participants521539
    Number [Participants with mortality event]
    57
    10.9%
    53
    9.8%
    3. Secondary Outcome
    TitleThe Number of Participants Who Experienced Adverse Events (AE)
    DescriptionSafety 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 FrameThrough 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 TitleArm A: FACArm B: TAC
    Arm/Group DescriptionFAC (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 CyclophosphamideTAC (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 Participants519532
    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
    TitleBest Score During Study for Global Health Status Scale
    DescriptionThe 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 Frame120 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleArm A: FACArm B: TAC
    Arm/Group DescriptionFAC (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 CyclophosphamideTAC (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 Participants519532
    Mean (Standard Deviation) [score on a scale]
    79.30
    (17.64)
    77.78
    (18.87)
    5. Secondary Outcome
    TitleNumber of Disease Free Survival Events in Hormone-receptor Positive and Human Epidermal Growth Factor Receptor 2 (HER2) Positive Status Subgroup
    DescriptionHormone-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 Frame10 year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleArm A: FACArm B: TAC
    Arm/Group DescriptionFAC (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 CyclophosphamideTAC (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 Participants2830
    Number [events]
    6
    6
    6. Secondary Outcome
    TitleDisease Free Survival in Hormonal Receptor Positive and HER2 Negative Subgroup
    DescriptionHormone-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 Frame10 year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleArm A: FACArm B: TAC
    Arm/Group DescriptionFAC (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 CyclophosphamideTAC (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 Participants209220
    Number [events]
    50
    37
    7. Secondary Outcome
    TitleDisease Free Survival in Hormonal Receptor Negative and HER2 Positive Subgroup
    DescriptionHormone-receptor status and HER2 receptor status was analysed in Paraffin-embedded tumor samples obtained at the time of surgery, and were processed centrally.
    Time Frame10 year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleArm A: FACArm B: TAC
    Arm/Group DescriptionFAC (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 CyclophosphamideTAC (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 Participants2422
    Number [events]
    6
    5
    8. Secondary Outcome
    TitleDisease Free Survival in Hormonal Receptor Negative and HER2 Negative Subgroup
    DescriptionHormone-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 Frame10 year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleArm A: FACArm B: TAC
    Arm/Group DescriptionFAC (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 CyclophosphamideTAC (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 Participants92103
    Number [events]
    29
    28

    Adverse Events

    Time FrameThrough 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 TitleArm A: FACArm B: TAC
    Arm/Group DescriptionFAC (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 CyclophosphamideTAC (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: FACArm B: TAC
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total57/519 (11%) 53/532 (10%)
    Serious Adverse Events
    Arm A: FACArm B: TAC
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total21/519 (4%) 119/532 (22.4%)
    Blood and lymphatic system disorders
    Anaemia1/519 (0.2%) 1/532 (0.2%)
    Blood bilirubin0/519 (0%) 1/532 (0.2%)
    Leukopenia0/519 (0%) 1/532 (0.2%)
    Neutropenia1/519 (0.2%) 5/532 (0.9%)
    Cardiac disorders
    Arrhythmia0/519 (0%) 1/532 (0.2%)
    Carotid artery thrombosis1/519 (0.2%) 0/532 (0%)
    Ear and labyrinth disorders
    Ear infection0/519 (0%) 1/532 (0.2%)
    Eye disorders
    Conjunctivitis0/519 (0%) 1/532 (0.2%)
    Gastrointestinal disorders
    Abdominal pain1/519 (0.2%) 1/532 (0.2%)
    Anal fissure0/519 (0%) 1/532 (0.2%)
    Constipation0/519 (0%) 1/532 (0.2%)
    Diarrhoea1/519 (0.2%) 6/532 (1.1%)
    Dyspepsia0/519 (0%) 1/532 (0.2%)
    Nausea1/519 (0.2%) 4/532 (0.8%)
    General disorders
    Asthenia0/519 (0%) 1/532 (0.2%)
    Fever in absence of infection12/519 (2.3%) 68/532 (12.8%)
    General physical health deterioration0/519 (0%) 1/532 (0.2%)
    Pyrexia0/519 (0%) 2/532 (0.4%)
    Infections and infestations
    Cellulitis0/519 (0%) 1/532 (0.2%)
    Device related infection0/519 (0%) 1/532 (0.2%)
    Localised infection0/519 (0%) 1/532 (0.2%)
    Postoperative wound infection0/519 (0%) 1/532 (0.2%)
    Skin infection0/519 (0%) 2/532 (0.4%)
    Wound infection0/519 (0%) 1/532 (0.2%)
    Investigations
    Febrile neutropenia0/519 (0%) 3/532 (0.6%)
    Metabolism and nutrition disorders
    Pancreatitis0/519 (0%) 1/532 (0.2%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Disease progression0/519 (0%) 1/532 (0.2%)
    Nervous system disorders
    Hypersensitivity0/519 (0%) 1/532 (0.2%)
    Reproductive system and breast disorders
    Breast cyst0/519 (0%) 1/532 (0.2%)
    Breast infection1/519 (0.2%) 0/532 (0%)
    Breast haematoma1/519 (0.2%) 0/532 (0%)
    Menorrhagia0/519 (0%) 1/532 (0.2%)
    Respiratory, thoracic and mediastinal disorders
    Bronchopneumonia0/519 (0%) 1/532 (0.2%)
    Cough0/519 (0%) 1/532 (0.2%)
    Respiratory tract infection0/519 (0%) 1/532 (0.2%)
    Tonsillitis0/519 (0%) 1/532 (0.2%)
    Skin and subcutaneous tissue disorders
    Erysipelas0/519 (0%) 1/532 (0.2%)
    Vascular disorders
    Deep vein thrombosis1/519 (0.2%) 0/532 (0%)
    Oedema peripheral0/519 (0%) 1/532 (0.2%)
    Thrombosis0/519 (0%) 1/532 (0.2%)
    Other (Not Including Serious) Adverse Events
    Arm A: FACArm B: TAC
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total519/519 (100%) 532/532 (100%)
    Blood and lymphatic system disorders
    Neutropenia9/519 (1.7%) 33/532 (6.2%)
    Thrombocytopenia2/519 (0.4%) 2/532 (0.4%)
    Cardiac disorders
    Arrhythmia6/519 (1.2%) 12/532 (2.3%)
    Cardiac failure0/519 (0%) 1/532 (0.2%)
    Eye disorders
    Conjunctivitis104/519 (20%) 108/532 (20.3%)
    Lacrimation increased18/519 (3.5%) 24/532 (4.5%)
    Gastrointestinal disorders
    Nausea387/519 (74.6%) 379/532 (71.2%)
    Stomatitis265/519 (51.1%) 292/532 (54.9%)
    Vomiting294/519 (56.6%) 292/532 (54.9%)
    Diarrhoea70/519 (13.5%) 147/532 (27.6%)
    Abdominal pain upper71/519 (13.7%) 88/532 (16.5%)
    Dyspepsia50/519 (9.6%) 57/532 (10.7%)
    Haemorrhoids6/519 (1.2%) 11/532 (2.1%)
    Flatulence2/519 (0.4%) 6/532 (1.1%)
    Anal abscess0/519 (0%) 1/532 (0.2%)
    General disorders
    Asthenia305/519 (58.8%) 387/532 (72.7%)
    Pain80/519 (15.4%) 118/532 (22.2%)
    Pyrexia46/519 (8.9%) 90/532 (16.9%)
    Decreased appetite69/519 (13.3%) 88/532 (16.5%)
    Weight increased10/519 (1.9%) 29/532 (5.5%)
    Bone pain1/519 (0.2%) 18/532 (3.4%)
    Back pain6/519 (1.2%) 17/532 (3.2%)
    Fatigue7/519 (1.3%) 4/532 (0.8%)
    Hyperhidrosis1/519 (0.2%) 3/532 (0.6%)
    Infections and infestations
    Urinary tract infection10/519 (1.9%) 11/532 (2.1%)
    Vaginal infection1/519 (0.2%) 5/532 (0.9%)
    Infection0/519 (0%) 3/532 (0.6%)
    Herpes zoster3/519 (0.6%) 2/532 (0.4%)
    Musculoskeletal and connective tissue disorders
    Myalgia15/519 (2.9%) 123/532 (23.1%)
    Arthralgia30/519 (5.8%) 108/532 (20.3%)
    Nervous system disorders
    Dysgeusia71/519 (13.7%) 85/532 (16%)
    Peripheral Sensory Neuropathy38/519 (7.3%) 83/532 (15.6%)
    Peripheral motor neuropathy2/519 (0.4%) 18/532 (3.4%)
    Photophobia1/519 (0.2%) 6/532 (1.1%)
    Visual impairment1/519 (0.2%) 3/532 (0.6%)
    Psychiatric disorders
    Insomnia24/519 (4.6%) 27/532 (5.1%)
    Affective disorder28/519 (5.4%) 25/532 (4.7%)
    Reproductive system and breast disorders
    Amenorrhoea70/519 (13.5%) 121/532 (22.7%)
    Menstruation irregular90/519 (17.3%) 103/532 (19.4%)
    Hot flush54/519 (10.4%) 74/532 (13.9%)
    Metrorrhagia2/519 (0.4%) 4/532 (0.8%)
    Vaginal haemorrhage1/519 (0.2%) 3/532 (0.6%)
    Respiratory, thoracic and mediastinal disorders
    Cough24/519 (4.6%) 26/532 (4.9%)
    Lung disorder14/519 (2.7%) 17/532 (3.2%)
    Dyspnoea3/519 (0.6%) 12/532 (2.3%)
    Chest pain6/519 (1.2%) 7/532 (1.3%)
    Pleural effusion0/519 (0%) 1/532 (0.2%)
    Pulmonary embolism1/519 (0.2%) 0/532 (0%)
    Skin and subcutaneous tissue disorders
    Alopecia508/519 (97.9%) 514/532 (96.6%)
    Nail disorder77/519 (14.8%) 102/532 (19.2%)
    Skin disorder51/519 (9.8%) 96/532 (18%)
    Erythema5/519 (1%) 10/532 (1.9%)
    Pigmentation disorder0/519 (0%) 2/532 (0.4%)
    Dry skin2/519 (0.4%) 1/532 (0.2%)
    Vascular disorders
    Oedema peripheral19/519 (3.7%) 101/532 (19%)
    Lymphoedema3/519 (0.6%) 13/532 (2.4%)
    Varicose vein0/519 (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/TitleScientific Director / Medical Lead / Project Manager
    OrganizationSpanish Breast Cancer Research Group
    Phone+34916592870
    Emailgeicam@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