Trial Outcomes & Findings for Docetaxel in Node Positive Adjuvant Breast Cancer (NCT NCT00688740)

Last Updated: 2011-02-16

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1491 participants

Primary outcome timeframe

up to 10 year follow-up

Results posted on

2011-02-16

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	TAC (Docetaxel) docetaxel in combination with doxorubicin and cyclophosphamide	FAC (5-fluorouracil) 5-fluorouracil in combination with doxorubicin and cyclophosphamide
Overall Study STARTED	745	746
Overall Study COMPLETED	679	711
Overall Study NOT COMPLETED	66	35

Reasons for withdrawal

Reasons for withdrawal
Measure	TAC (Docetaxel) docetaxel in combination with doxorubicin and cyclophosphamide	FAC (5-fluorouracil) 5-fluorouracil in combination with doxorubicin and cyclophosphamide
Overall Study Adverse Event	45	8
Overall Study Death	2	2
Overall Study Lost to Follow-up	0	1
Overall Study Consent Withdrawn	17	17
Overall Study Breast Cancer Relapse	1	4
Overall Study Violation of Inclusion Criteria	1	3

Baseline Characteristics

Docetaxel in Node Positive Adjuvant Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TAC (Docetaxel) n=745 Participants docetaxel in combination with doxorubicin and cyclophosphamide	FAC (5-fluorouracil) n=746 Participants 5-fluorouracil in combination with doxorubicin and cyclophosphamide	Total n=1491 Participants Total of all reporting groups
Age, Categorical Between 18 and 65 years	697 Participants n=99 Participants	705 Participants n=107 Participants	1402 Participants n=206 Participants
Age, Categorical >=65 years	48 Participants n=99 Participants	41 Participants n=107 Participants	89 Participants n=206 Participants
Sex: Female, Male Female	745 Participants n=99 Participants	746 Participants n=107 Participants	1491 Participants n=206 Participants
Sex: Female, Male Male	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Number of Positive Nodes 1-3 Positive Nodes	467 participants n=99 Participants	459 participants n=107 Participants	926 participants n=206 Participants
Number of Positive Nodes 4 or More Positive Nodes	278 participants n=99 Participants	287 participants n=107 Participants	565 participants n=206 Participants

PRIMARY outcome

Timeframe: 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)

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.

Outcome measures

Outcome measures
Measure	TAC (Docetaxel) n=745 Participants docetaxel in combination with doxorubicin and cyclophosphamide	FAC (5-fluorouracil) n=746 Participants 5-fluorouracil in combination with doxorubicin and cyclophosphamide
Number of Participants With Disease-Free Survival Events	287 Participants Interval 0.579 to 0.65	333 Participants Interval 0.513 to 0.586

SECONDARY outcome

Timeframe: up to 10 year follow-up

Overall Survival - time from the date of randomization up to the date of death of any cause.

Outcome measures

Outcome measures
Measure	TAC (Docetaxel) n=745 Participants docetaxel in combination with doxorubicin and cyclophosphamide	FAC (5-fluorouracil) n=746 Participants 5-fluorouracil in combination with doxorubicin and cyclophosphamide
Number of Participants With Overall Survival Events	188 Participants Interval 0.724 to 0.786	241 Participants Interval 0.651 to 0.719

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	TAC (Docetaxel) n=745 Participants docetaxel in combination with doxorubicin and cyclophosphamide	FAC (5-fluorouracil) n=746 Participants 5-fluorouracil in combination with doxorubicin and cyclophosphamide
Number of Participants With Second Primary Malignancies (Toxicity)	67 Participants	66 Participants

Adverse Events

TAC (Docetaxel)

Serious events: 267 serious events

Other events: 744 other events

Deaths: 0 deaths

FAC (5-fluorouracil)

Serious events: 67 serious events

Other events: 734 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

International Clinical Development Study Director

sanofi-aventis

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee No publication of the study will be made without approval of the advisory board of the Breast Cancer International Research Group and Rhone- Poulenc Rorer.
Publication restrictions are in place

Restriction type: OTHER

Measure	TAC (Docetaxel) n=744 participants at risk docetaxel in combination with doxorubicin and cyclophosphamide	FAC (5-fluorouracil) n=736 participants at risk 5-fluorouracil in combination with doxorubicin and cyclophosphamide
Skin and subcutaneous tissue disorders Any skin and subcutaneous tissue disorders	98.7% 734/744 • from date of randomization until the completion of the 10-year follow-up period.	97.6% 718/736 • from date of randomization until the completion of the 10-year follow-up period.
Skin and subcutaneous tissue disorders Alopecia	97.8% 728/744 • from date of randomization until the completion of the 10-year follow-up period.	97.1% 715/736 • from date of randomization until the completion of the 10-year follow-up period.
Skin and subcutaneous tissue disorders Skin disorder	23.7% 176/744 • from date of randomization until the completion of the 10-year follow-up period.	14.3% 105/736 • from date of randomization until the completion of the 10-year follow-up period.
Skin and subcutaneous tissue disorders Nail disorder	18.1% 135/744 • from date of randomization until the completion of the 10-year follow-up period.	14.0% 103/736 • from date of randomization until the completion of the 10-year follow-up period.
Gastrointestinal disorders Any gastrointestinal disorders	95.8% 713/744 • from date of randomization until the completion of the 10-year follow-up period.	96.3% 709/736 • from date of randomization until the completion of the 10-year follow-up period.
Gastrointestinal disorders Nausea	80.5% 599/744 • from date of randomization until the completion of the 10-year follow-up period.	87.9% 647/736 • from date of randomization until the completion of the 10-year follow-up period.
Gastrointestinal disorders Stomatitis	68.3% 508/744 • from date of randomization until the completion of the 10-year follow-up period.	50.8% 374/736 • from date of randomization until the completion of the 10-year follow-up period.
Gastrointestinal disorders Vomiting	44.0% 327/744 • from date of randomization until the completion of the 10-year follow-up period.	59.2% 436/736 • from date of randomization until the completion of the 10-year follow-up period.
Gastrointestinal disorders Constipation	36.4% 271/744 • from date of randomization until the completion of the 10-year follow-up period.	34.6% 255/736 • from date of randomization until the completion of the 10-year follow-up period.
Gastrointestinal disorders Diarrhoea	34.8% 259/744 • from date of randomization until the completion of the 10-year follow-up period.	27.9% 205/736 • from date of randomization until the completion of the 10-year follow-up period.
Gastrointestinal disorders Dyspepsia	23.9% 178/744 • from date of randomization until the completion of the 10-year follow-up period.	17.9% 132/736 • from date of randomization until the completion of the 10-year follow-up period.
Gastrointestinal disorders Haemorrhoids	7.7% 57/744 • from date of randomization until the completion of the 10-year follow-up period.	4.8% 35/736 • from date of randomization until the completion of the 10-year follow-up period.
Gastrointestinal disorders Abdominal pain upper	5.9% 44/744 • from date of randomization until the completion of the 10-year follow-up period.	3.0% 22/736 • from date of randomization until the completion of the 10-year follow-up period.
Gastrointestinal disorders Dry mouth	4.8% 36/744 • from date of randomization until the completion of the 10-year follow-up period.	5.8% 43/736 • from date of randomization until the completion of the 10-year follow-up period.
General disorders Any general disorders and administration site conditions	90.5% 673/744 • from date of randomization until the completion of the 10-year follow-up period.	82.9% 610/736 • from date of randomization until the completion of the 10-year follow-up period.
General disorders Asthenia	79.6% 592/744 • from date of randomization until the completion of the 10-year follow-up period.	69.7% 513/736 • from date of randomization until the completion of the 10-year follow-up period.
General disorders Pain	41.9% 312/744 • from date of randomization until the completion of the 10-year follow-up period.	35.9% 264/736 • from date of randomization until the completion of the 10-year follow-up period.
General disorders Oedema peripheral	33.6% 250/744 • from date of randomization until the completion of the 10-year follow-up period.	12.4% 91/736 • from date of randomization until the completion of the 10-year follow-up period.
General disorders Pyrexia	20.4% 152/744 • from date of randomization until the completion of the 10-year follow-up period.	11.8% 87/736 • from date of randomization until the completion of the 10-year follow-up period.
General disorders Injection site reaction	13.3% 99/744 • from date of randomization until the completion of the 10-year follow-up period.	12.0% 88/736 • from date of randomization until the completion of the 10-year follow-up period.
General disorders Chills	7.1% 53/744 • from date of randomization until the completion of the 10-year follow-up period.	3.9% 29/736 • from date of randomization until the completion of the 10-year follow-up period.
Nervous system disorders Any nervous system disorders	57.4% 427/744 • from date of randomization until the completion of the 10-year follow-up period.	43.2% 318/736 • from date of randomization until the completion of the 10-year follow-up period.
Nervous system disorders Dysgeusia	27.7% 206/744 • from date of randomization until the completion of the 10-year follow-up period.	15.2% 112/736 • from date of randomization until the completion of the 10-year follow-up period.
Nervous system disorders Peripheral sensory neuropathy	24.9% 185/744 • from date of randomization until the completion of the 10-year follow-up period.	9.5% 70/736 • from date of randomization until the completion of the 10-year follow-up period.
Nervous system disorders Headache	20.6% 153/744 • from date of randomization until the completion of the 10-year follow-up period.	23.0% 169/736 • from date of randomization until the completion of the 10-year follow-up period.
Nervous system disorders Dizziness	8.5% 63/744 • from date of randomization until the completion of the 10-year follow-up period.	6.8% 50/736 • from date of randomization until the completion of the 10-year follow-up period.
Reproductive system and breast disorders Any reproductive system and breast disorders	41.3% 307/744 • from date of randomization until the completion of the 10-year follow-up period.	36.4% 268/736 • from date of randomization until the completion of the 10-year follow-up period.
Reproductive system and breast disorders Amenorrhoea	28.5% 212/744 • from date of randomization until the completion of the 10-year follow-up period.	18.5% 136/736 • from date of randomization until the completion of the 10-year follow-up period.
Reproductive system and breast disorders Menstruation irregular	28.4% 211/744 • from date of randomization until the completion of the 10-year follow-up period.	22.4% 165/736 • from date of randomization until the completion of the 10-year follow-up period.
Infections and infestations Any infections and infestations	39.7% 295/744 • from date of randomization until the completion of the 10-year follow-up period.	39.8% 293/736 • from date of randomization until the completion of the 10-year follow-up period.
Infections and infestations Nasopharyngitis	6.0% 45/744 • from date of randomization until the completion of the 10-year follow-up period.	8.4% 62/736 • from date of randomization until the completion of the 10-year follow-up period.
Infections and infestations Upper respiratory tract infection	4.7% 35/744 • from date of randomization until the completion of the 10-year follow-up period.	7.2% 53/736 • from date of randomization until the completion of the 10-year follow-up period.
Musculoskeletal and connective tissue disorders Any musculoskeletal and connective tissue disorders	39.0% 290/744 • from date of randomization until the completion of the 10-year follow-up period.	20.7% 152/736 • from date of randomization until the completion of the 10-year follow-up period.
Musculoskeletal and connective tissue disorders Myalgia	26.7% 199/744 • from date of randomization until the completion of the 10-year follow-up period.	9.9% 73/736 • from date of randomization until the completion of the 10-year follow-up period.
Musculoskeletal and connective tissue disorders Arthralgia	19.4% 144/744 • from date of randomization until the completion of the 10-year follow-up period.	9.1% 67/736 • from date of randomization until the completion of the 10-year follow-up period.
Respiratory, thoracic and mediastinal disorders Any respiratory, thoracic and mediastinal disorders	37.6% 280/744 • from date of randomization until the completion of the 10-year follow-up period.	26.6% 196/736 • from date of randomization until the completion of the 10-year follow-up period.
Respiratory, thoracic and mediastinal disorders Lung disorder	15.7% 117/744 • from date of randomization until the completion of the 10-year follow-up period.	8.7% 64/736 • from date of randomization until the completion of the 10-year follow-up period.
Respiratory, thoracic and mediastinal disorders Cough	13.4% 100/744 • from date of randomization until the completion of the 10-year follow-up period.	9.8% 72/736 • from date of randomization until the completion of the 10-year follow-up period.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	8.1% 60/744 • from date of randomization until the completion of the 10-year follow-up period.	7.2% 53/736 • from date of randomization until the completion of the 10-year follow-up period.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	5.2% 39/744 • from date of randomization until the completion of the 10-year follow-up period.	3.7% 27/736 • from date of randomization until the completion of the 10-year follow-up period.
Vascular disorders Any vascular disorders	36.4% 271/744 • from date of randomization until the completion of the 10-year follow-up period.	26.4% 194/736 • from date of randomization until the completion of the 10-year follow-up period.
Vascular disorders Hot flush	24.7% 184/744 • from date of randomization until the completion of the 10-year follow-up period.	20.0% 147/736 • from date of randomization until the completion of the 10-year follow-up period.
Vascular disorders Flushing	6.6% 49/744 • from date of randomization until the completion of the 10-year follow-up period.	3.5% 26/736 • from date of randomization until the completion of the 10-year follow-up period.
Psychiatric disorders Any psychiatric disorders	28.8% 214/744 • from date of randomization until the completion of the 10-year follow-up period.	23.1% 170/736 • from date of randomization until the completion of the 10-year follow-up period.
Psychiatric disorders Insomnia	16.4% 122/744 • from date of randomization until the completion of the 10-year follow-up period.	11.3% 83/736 • from date of randomization until the completion of the 10-year follow-up period.
Psychiatric disorders Affective disorder	11.0% 82/744 • from date of randomization until the completion of the 10-year follow-up period.	10.3% 76/736 • from date of randomization until the completion of the 10-year follow-up period.
Eye disorders Any eye disorders	26.1% 194/744 • from date of randomization until the completion of the 10-year follow-up period.	22.7% 167/736 • from date of randomization until the completion of the 10-year follow-up period.
Eye disorders Lacrimation increased	11.7% 87/744 • from date of randomization until the completion of the 10-year follow-up period.	7.1% 52/736 • from date of randomization until the completion of the 10-year follow-up period.
Metabolism and nutrition disorders Any metabolism and nutrition disorders	24.9% 185/744 • from date of randomization until the completion of the 10-year follow-up period.	19.0% 140/736 • from date of randomization until the completion of the 10-year follow-up period.
Metabolism and nutrition disorders Decreased appetite	21.6% 161/744 • from date of randomization until the completion of the 10-year follow-up period.	17.7% 130/736 • from date of randomization until the completion of the 10-year follow-up period.
Investigations Any investigations	23.0% 171/744 • from date of randomization until the completion of the 10-year follow-up period.	19.6% 144/736 • from date of randomization until the completion of the 10-year follow-up period.
Investigations Weight increased	17.6% 131/744 • from date of randomization until the completion of the 10-year follow-up period.	14.7% 108/736 • from date of randomization until the completion of the 10-year follow-up period.
General disorders Fever in absence of infection	15.1% 112/744 • from date of randomization until the completion of the 10-year follow-up period.	5.4% 40/736 • from date of randomization until the completion of the 10-year follow-up period.
Immune system disorders Any immune system disorders	12.5% 93/744 • from date of randomization until the completion of the 10-year follow-up period.	3.3% 24/736 • from date of randomization until the completion of the 10-year follow-up period.
Immune system disorders Hypersensitivity	11.0% 82/744 • from date of randomization until the completion of the 10-year follow-up period.	2.9% 21/736 • from date of randomization until the completion of the 10-year follow-up period.
Cardiac disorders Any cardiac disorders	10.3% 77/744 • from date of randomization until the completion of the 10-year follow-up period.	6.9% 51/736 • from date of randomization until the completion of the 10-year follow-up period.
Cardiac disorders Arrhythmia	6.2% 46/744 • from date of randomization until the completion of the 10-year follow-up period.	4.8% 35/736 • from date of randomization until the completion of the 10-year follow-up period.