Phase III study of doxorubicin/cyclophosphamide with concomitant versus sequential docetaxel as adjuvant treatment in patients with human epidermal growth factor receptor 2-normal, node-positive breast cancer: BCIRG-005 trial
Eiermann W.,Red Cross |
Eiermann W.,All Ireland Co Operative Oncology Research Group |
Eiermann W.,Hospital Universitario San Carlos |
Eiermann W.,Mount Medical Center |
And 212 more authors.
Journal of Clinical Oncology | Year: 2011
Purpose: Anthracyclines, taxanes, and alkylating agents are among the most active agents in treatment of adjuvant breast cancer (BC), but the optimal schedule for their administration is unknown. We performed an adjuvant trial to compare the sequential regimen of doxorubicin with cyclophosphamide (AC) followed by docetaxel (ie, AC>T) with the combination regimen of TAC. Patients and Methods: Women with node-positive, human epidermal growth factor receptor 2-nonamplified, operable BC were stratified by number of axillary nodes and hormone receptor status and were randomly assigned to adjuvant chemotherapy with six cycles of TAC (75/50/500 mg/m 2 every 3 weeks) or four cycles of AC (60/600 mg/m 2 every 3 weeks) followed by four doses of docetaxel at 100 mg/m 2 every 3 weeks (AC>T). After completion of chemotherapy, radiation therapy was given as indicated, and patients with hormone receptor (HR) -positive disease received adjuvant hormonal therapy with tamoxifen and/or aromatase inhibitors. Results: In 30 months, 3,298 patients were enrolled (n = 1,649 in each arm). The major baseline characteristics were well balanced between the groups. At a median follow-up of 65 months, estimated 5-year disease-free survival rates were 79% in both groups (log-rank P = .98; hazard ratio [HR], 1.0; 95%CI, 0.86 to 1.16), and 5-year overall survival rates for both arms were 88% and 89%, respectively (log-rank P = .37; HR, 0.91; 95% CI, 0.75 to 1.11). TAC was associated with more febrile neutropenia and thrombocytopenia, and AC>T was associated with more sensory neuropathy, nail changes, and myalgia. The incidence of neutropenic infection was similar in both groups. Conclusion: The sequential and combination regimens incorporating three drugs were equally effective but differed in toxicity profile. © 2011 by American Society of Clinical Oncology.
Mackey J.R.,Cross Cancer Institute |
Pienkowski T.,Center of Oncology of Poland |
Crown J.,Dublin City University |
Sadeghi S.,University of California at Los Angeles |
And 15 more authors.
Annals of Oncology | Year: 2016
Background: The optimal regimen for adjuvant breast cancer chemotherapy is undefined. We compared sequential to concurrent combination of doxorubicin and cyclophosphamide with docetaxel chemotherapy in women with nodepositive non-metastatic breast cancer. We report the final, 10-year analysis of disease-free survival (DFS), overall survival (OS), and long-term safety. Patients and methods: A total of 3298 women with HER2 nonamplified breast cancer were randomized to doxorubicin and cyclophosphamide every 3 weeks for four cycles followed by docetaxel (AC→T) every 3 weeks for four cycles or docetaxel, doxorubicin, and cyclophosphamide (TAC) every 3 weeks for six cycles. The patients received standard radiotherapy and endocrine therapy and were followed up for 10 years with annual clinical evaluation and mammography. Results: The 10-year DFS rates were 66.5% in the AC→T arm and 66.3% in the TAC arm (P = 0.749). OS was 79.9% in the AC→T arm and 78.9% in the TAC arm (P = 0.506). TAC was associated with higher rates of febrile neutropenia, although G-CSF primary prophylaxis greatly reduced this risk. AC→T was associated with a higher rate of myalgia, hand-foot syndrome, fluid retention, and sensory neuropathy. Conclusion: This 10-year analysis of the BCIRG-005 trial confirmed that the efficacy of TAC was not superior to AC→T in women with node-positive early breast cancer. The toxicity profiles differ between arms and were consistent with previous reports. The TAC regimen with G-CSF support provides shorter adjuvant treatment duration with less toxicity. Trial Registration: ClinicalTrials.gov Identifier NCT00312208. © The Author 2016.