Adjuvant docetaxel, doxorubicin, and cyclophosphamide in node-positive breast cancer: 10-year follow-up of the phase 3 randomised BCIRG 001 trial

Cross Cancer Institute, Edmonton, AB, Canada.
The Lancet Oncology (Impact Factor: 24.69). 12/2012; 14(1). DOI: 10.1016/S1470-2045(12)70525-9
Source: PubMed


BACKGROUND: We compared standard adjuvant anthracycline chemotherapy with anthracycline-taxane combination chemotherapy in women with operable node-positive breast cancer. Here we report the final, 10-year follow-up analysis of disease-free survival, overall survival, and long-term safety. METHODS: BCIRG 001 was an open label, phase 3, multicentre trial in which 1491 patients aged 18-70 years with node-positive, early breast cancer and a Karnofsky score of 80% or more were randomly assigned to adjuvant treatment with docetaxel, doxorubicin, and cyclophosphamide (TAC) or fluorouracil, doxorubicin, and cyclophosphamide (FAC) every 3 weeks for six cycles. Randomisation was stratified according to institution and number of involved axillary lymph nodes per patient (one to three vs four or more). Disease-free survival was the primary endpoint and was defined as the interval between randomisation and breast cancer relapse, second primary cancer, or death, whichever occurred first. Efficacy analyses were based on the intention-to-treat principle. BCIRG 001 is registered with, number NCT00688740. FINDINGS: Enrolement took place between June 11, 1997 and June 3, 1999; 745 patients were assigned to receive TAC and 746 patients were assigned to receive FAC. After a median follow-up of 124 months (IQR 90-126), disease-free survival was 62% (95% CI 58-65) for patients in the TAC group and 55% (51-59) for patients in the FAC group (hazard ratio [HR] 0·80, 95% CI 0·68-0·93; log-rank p=0·0043). 10-year overall survival was 76% (95% CI 72-79) for patients in the TAC group and 69% (65-72) for patients in the FAC group (HR 0·74, 0·61-0·90; log-rank p=0·0020). TAC improved disease-free survival relative to FAC irrespective of nodal, hormone receptor, and HER2 status, although not all differences were significant in these subgroup analyses. Grade 3-4 heart failure occurred in 26 (3%) patients in the TAC group and 17 (2%) patients in the FAC group, and caused death in two patients in the TAC group and four patients in the FAC group. A substantial decrease in left ventricular ejection fraction (defined as a relative decrease from baseline of 20% or more) was seen in 58 (17%) patients who received TAC and 41 (15%) patients who received FAC. Six patients who received TAC developed leukaemia or myelodysplasia, as did three patients who received FAC. INTERPRETATION: Our results provide evidence that the initial therapeutic outcomes seen at the 5-year follow-up with a docetaxel-containing adjuvant regimen are maintained at 10 years. However, a substantial percentage of patients had a decrease in left ventricular ejection fraction, probably caused by anthracycline therapy, which warrants further investigation. FUNDING: Sanofi.

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Available from: Robert E Coleman, Oct 02, 2015
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    • "Clinical trials have strict and mandatory diagnostic, management and follow-up protocols. They generate Disease-Free Survival (DFS) and Overall Survival (OS) data at 3 or 5 years with some updates at 8 or 10 years,3-5 and provide evidence-based results that are used for clinical practice guidelines. Meta-analyses combine data from clinical trials and present further conclusions on mortality and survival data at 5, 10, 15 years, or even longer.6 "
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    ABSTRACT: Background: Information on outcome of breast cancer patients treated in the community is scarce. Data on outcome of patients treated in real-life clinical practice may provide useful information for performance improvement. Methods: Study population is from a single institution practice at the American University of Beirut Medical Center. Demographics, clinical characteristics and survival data on patients diagnosed 1997-2010 in two IRB-approved studies were entered and analyzed on SPSS program. Survival was estimated using Kaplan Meier Method. Findings: Total was 519 patients. 23.9% had stage I, 39.7% stage II, 30.4% Stage III and 6% stage IV. ER positive in 74.4% of patients. 30.6% of patients <35 had TNBC compared to 12.3% for the whole group. 45.9% of non-metastatic patients had breast-conserving therapy (BCT). BCT rates increased to 64% during the second half of the study, coinciding with increasing awareness and changing cultural mores. 5-year and 10-year overall survivals for stage I were 98.9% and 80.5%, 89.2% and 70.7% for stage II, 67.6% and 35.5% for stage III, and 39.1% and 26.1% for stage IV respectively. Interpretation: Patients treated outside clinical trials in a multidisciplinary fashion according to guidelines have comparable, and at times better, survival compared to data from trials or population statistics. Locally generated outcome data could be valuable for evaluating results of treatment at individual practices for the purpose of quality assessment and improvement. Our data also provides report of increased rate of breast conserving surgery from Middle East.
    Journal of Cancer 06/2014; 5(6):491-8. DOI:10.7150/jca.9216 · 3.27 Impact Factor
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    • "As a result, anthracycline- and taxane-based chemotherapeutic regimens have become the standard of care in early stage breast cancers. Among the most active adjuvant chemotherapy regimens, the docetaxel-based combinations of docetaxel, doxorubicin, and cyclophosphamide (TAC),6–8 docetaxel with cyclophosphamide,9,10 sequential anthracycline (eg, FEC [5-fluorouracil, epirubicin, and cyclophosphamide]) followed by docetaxel monotherapy,11–14 and docetaxel, carboplatin, and trastuzumab15 are most commonly used. "
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    ABSTRACT: The taxane chemotherapeutic agent docetaxel has been utilized in the management of breast cancer in the adjuvant, neoadjuvant and metastatic setting. Although well tolerated by the majority of patients, docetaxel toxicity may limit the dose which can be administered. Adverse events include infusion reactions, febrile neutropenia, fatigue, fluid retention, pneumonitis, cutaneous and nail toxicity, epiphora and lacrimal duct stenosis, gastrointestinal complications, and neuropathies. In this review, we explore these complications and how they can be effectively managed to improve patient quality of life during and following docetaxel therapy.
    Cancer Management and Research 05/2014; 6(1):253-259. DOI:10.2147/CMAR.S40601
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    • "The present study was primarily initiated to evaluate the cardiac safety of bevacizumab when given in combination with a standard-of-care anthracycline-based treatment—docetaxel, doxorubicin, cyclophosphamide (TAC) (Mackey et al. 2013)—in the adjuvant setting. At the time of study initiation, larger studies, such as Eastern Cooperative Oncology Group (ECOG) E5103 (National Cancer Institute), were being planned to evaluate bevacizumab in adjuvant, HER2-negative breast cancer patients. "
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    ABSTRACT: PurposeAdding antiangiogenic therapy to standard chemotherapy has improved response rates and progression-free survival in metastatic breast cancer (BC) patients. This phase II study evaluated cardiac safety of bevacizumab with/without trastuzumab with two docetaxel-based regimens in early BC.Methods127 women with non-metastatic node-positive or high-risk node-negative BC were enrolled. Women with human epidermal growth factor receptor 2 (HER2)-negative BC (n = 93) received docetaxel/doxorubicin/cyclophosphamide (TAC) + bevacizumab, while women with HER2-positive disease (n = 34) received docetaxel/carboplatin/trastuzumab (TCH) + bevacizumab, every 3 weeks for six cycles. Maintenance therapy with bevacizumab alone or bevacizumab plus trastuzumab, respectively, was given every 3 weeks for 52 weeks. The primary objective was to evaluate cardiac safety, as measured by the incidence of ≥ grade 3 clinical congestive heart failure (CHF); the secondary objective was assessment of safety and toxicity.ResultsAt least one cardiac adverse event (AE; CHF, cardiomyopathy, or left ventricular dysfunction) was reported in 26.1% of TAC (n = 92) and 17.6% of TCH subjects (n = 34); there were no cardiac deaths. ≥ Grade 3 clinical CHF was observed in 4.3% in the TAC plus bevacizumab stratum and 0% in the TCH plus bevacizumab stratum. A ≥ grade 3 treatment-emergent AE (any kind) related to study treatment was observed in 59.8% in the TAC with bevacizumab and 52.9% in the TCH plus bevacizumab stratum.ConclusionAdding bevacizumab to a docetaxel-based regimen with trastuzumab did not appear to increase cardiotoxicity.Trial Identifier: NCT00446030, registered March 8, 2007.
    SpringerPlus 05/2014; 3(1):244. DOI:10.1186/2193-1801-3-244
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