Dose-dense adjuvant chemotherapy for primary breast cancer

Adjuvant chemotherapy has been proven to reduce significantly the risk for relapse and death in women with operable breast cancer. Nevertheless, the prognosis for patients presenting with extensive axillary lymph node involvement remains suboptimal. In an attempt to improve on the efficacy of existing chemotherapy, a phase III intergroup trial led by the Cancer and Leukemia Group B (CALGB 97-41) was designed, which tested a mathematical model of tumor growth based on the Norton–Simon hypothesis. This hypothesis, developed about 3 decades ago, and the kinetic model derived from it, created the basis of the concepts of dose density and sequential therapy, both of which were tested in CALGB 97-41. This large prospective randomized trial demonstrated that shortening the time interval between each chemotherapy cycle while maintaining the same dose size resulted in significant improvements in disease-free and overall survival in patients with node-positive breast carcinoma. This finding is highly relevant and has immediate implications for clinical practice

International Guidelines for Management of Metastatic Breast Cancer: Combination vs Sequential Single-Agent Chemotherapy

Compared with treatment options for early-stage breast cancer, few data exist regarding the optimal use of chemotherapy for metastatic breast cancer (MBC). The choice of using a combination of cytotoxic chemotherapies vs sequential single agents is controversial. At the 6th European Breast Cancer Conference, the European School of Oncology Metastatic Breast Cancer Task Force convened an open debate on the relative benefits of combination vs sequential therapy. Based on the available data, the Task Force recommends sequential monotherapy as the preferred choice in advanced disease, in the absence of rapid clinical progression, life-threatening visceral metastases, or the need for rapid symptom and/or disease control. Patient- and disease-related factors should be used to choose between combination and sequential single-agent chemotherapy for MBC. Additional research is needed to determine the impact of therapy on patient-rated quality of life and to identify predictive factors that can be used to guide therapy

Epirubicin and cyclophosphamide versus epirubicin and docetaxel as first-line therapy for women with metastatic breast cancer: final results of a randomised phase III trial

Patients and methods: Patients (n = 240) were randomly assigned to receive either ED (epirubicin 75 mg/m(2) and docetaxel 75 mg/m(2)) or EC (epirubicin 90 mg/m(2) and cyclophosphamide 600 mg/m(2)). The primary end point was objective response rate (ORR). Secondary end points were progression-free survival (PFS), overall survival (OS), and safety. Results: ORR for patients randomly assigned to receive EC and ED were 42% and 47%, respectively (P = 0.63). Median PFS [10.1 versus 10.3 months; hazard ratio (HR) 0.98; log-rank P = 0.38] and OS (19.9 versus 30.0 months; HR 0.663; log-rank P = 0.21) were comparable in both arms. Although grade 3/4 leucopenia occurred more frequently with ED (81% versus 73%; P = 0.01), there were no significant differences in the incidence of febrile neutropenia and grade 3/4 infections. Grade 3/4 non-haematologic toxicity was infrequent in both arms. Congestive heart failure was observed in one patient in each arm. Conclusion: In this randomised trial, no differences in the efficacy study end points were observed between the two treatment arms