Breast Cancer
Conditions
Keywords
adjuvant treatment
Brief summary
The purpose of this study was to compare disease-free survival after treatment with docetaxel in combination with doxorubicin and cyclophosphamide to 5-fluorouracil in combination with doxorubicin and cyclophosphamide in operable breast cancer patients with positive axillary lymph nodes.
Detailed description
In addition to the 5-year analysis conducted in September 2003, two other analyses were planned when 590 and 700 Disease Free Survival events occurred. However, due to the lower than predicted DFS event rate, and in agreement with FDA and EMA, a time-based final analysis at 10 years was considered more appropriate than an event-based (700 Disease Free Survival events) analysis.
Interventions
DRUGDocetaxel
intravenous
DRUG5-fluorouracil
intravenous
DRUGDoxorubicin
intravenous
DRUGCyclophosphamide
intravenous
Sponsors
Cancer International Research Group (CIRG)
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Histologically proven breast cancer (invasive adenocarcinoma with at least one axillary lymph node showing evidence of tumor among a minimum of six resected lymph nodes). * Definitive surgical treatment must be either mastectomy, or breast conserving surgery with axillary lymph node dissection for operable breast cancer. Margins of resected specimen from definitive surgery must be histologically free of invasive adenocarcinoma and ductal carcinoma.
Exclusion criteria
* Prior systemic anticancer therapy for breast cancer (immunotherapy, hormonotherapy, chemotherapy). * Prior anthracycline therapy or taxoids (paclitaxel, docetaxel) for any malignancy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Disease-Free Survival Events | up to 10 year follow-up | Disease-Free Survival (DFS)- are defined as local, regional or metastatic relapse or the date of second primary cancer or death from any cause whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Overall Survival Events | up to 10 year follow-up | Overall Survival - time from the date of randomization up to the date of death of any cause. |
| Number of Participants With Second Primary Malignancies (Toxicity) | up to 10 year follow-up | Toxicity (second primary malignancies)- defined as histopathologically proven cancer, excluding nonmelanomatous skin cancer, in situ carcinoma of the cervix, and in situ carcinoma of the breast. |
Countries
Argentina, Austria, Brazil, Canada, Czechia, Egypt, France, Germany, Greece, Hungary, Israel, Poland, Portugal, Slovakia, South Africa, Spain, Sweden, United Kingdom, United States, Uruguay
Participant flow
Recruitment details
Between June 1997 and June 1999, 1491 women from 20 countries were enrolled in the study. The last patient last visit occurred in January 2010.
Pre-assignment details
Eleven women (1 who had been randomly assigned to receive TAC and 10 assigned to receive FAC) did not receive any treatment for the following reasons: 8 withdrew consent, 1 was lost to follow-up, and 2 did not receive treatment for other reasons. In total 1480 patients (744 in the TAC group and 736 in the FAC group) were treated.
Participants by arm
| Arm | Count |
|---|---|
| TAC (Docetaxel) docetaxel in combination with doxorubicin and cyclophosphamide | 745 |
| FAC (5-fluorouracil) 5-fluorouracil in combination with doxorubicin and cyclophosphamide | 746 |
| Total | 1,491 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 45 | 8 |
| Overall Study | Breast Cancer Relapse | 1 | 4 |
| Overall Study | Consent Withdrawn | 17 | 17 |
| Overall Study | Death | 2 | 2 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Violation of Inclusion Criteria | 1 | 3 |
Baseline characteristics
| Characteristic | TAC (Docetaxel) | FAC (5-fluorouracil) | Total |
|---|---|---|---|
| Age, Categorical >=65 years | 48 Participants | 41 Participants | 89 Participants |
| Age, Categorical Between 18 and 65 years | 697 Participants | 705 Participants | 1402 Participants |
| Number of Positive Nodes 1-3 Positive Nodes | 467 participants | 459 participants | 926 participants |
| Number of Positive Nodes 4 or More Positive Nodes | 278 participants | 287 participants | 565 participants |
| Sex: Female, Male Female | 745 Participants | 746 Participants | 1491 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 744 / 744 | 734 / 736 |
| serious Total, serious adverse events | 267 / 744 | 67 / 736 |
Outcome results
Primary
Number of Participants With Disease-Free Survival Events
Disease-Free Survival (DFS)- are defined as local, regional or metastatic relapse or the date of second primary cancer or death from any cause whichever occurs first.
Time frame: up to 10 year follow-up
Population: The study was originally designed to have 90% power to detect a 26% risk reduction of relapsing for TAC compared to FAC (hazard ratio=0.74)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAC (Docetaxel) | Number of Participants With Disease-Free Survival Events | 287 Participants |
| FAC (5-fluorouracil) | Number of Participants With Disease-Free Survival Events | 333 Participants |
p-value: 0.004395% CI: [0.679, 0.932]Log Rank
Secondary
Number of Participants With Overall Survival Events
Overall Survival - time from the date of randomization up to the date of death of any cause.
Time frame: up to 10 year follow-up
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAC (Docetaxel) | Number of Participants With Overall Survival Events | 188 Participants |
| FAC (5-fluorouracil) | Number of Participants With Overall Survival Events | 241 Participants |
p-value: 0.00295% CI: [0.613, 0.898]Log Rank
Secondary
Number of Participants With Second Primary Malignancies (Toxicity)
Toxicity (second primary malignancies)- defined as histopathologically proven cancer, excluding nonmelanomatous skin cancer, in situ carcinoma of the cervix, and in situ carcinoma of the breast.
Time frame: up to 10 year follow-up
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAC (Docetaxel) | Number of Participants With Second Primary Malignancies (Toxicity) | 67 Participants |
| FAC (5-fluorouracil) | Number of Participants With Second Primary Malignancies (Toxicity) | 66 Participants |