PURPOSE: Theoretical considerations and clinical experience suggest that dose-dense chemotherapy may be superior to other approaches using the same drugs. We studied a dose-dense combination of doxorubicin and cyclophosphamide, with or without fluorouracil, as adjuvant therapy. PATIENTS AND METHODS: Patients with resected breast cancer were treated if they were node-positive and estrogen receptor-negative, positive for overexpression of Her-2-neu, or had four or more involved nodes. Doxorubicin was given weekly to a total dose of 480 mg/m(2). Cyclophosphamide 60 mg/m(2) was given daily by mouth during the period of doxorubicin treatment. The first 30 patients received fluorouracil at 300 mg/m(2)/wk intravenously concurrently with doxorubicin administration. In the last 22, it was omitted because of symptomatic hand-foot syndrome in the majority of patients. Filgrastim (granulocyte colony-stimulating factor [G-CSF]) was administered during chemotherapy every day except the day of intravenous administration and continued until 1 week after the completion of the chemotherapy. RESULTS:Between October 20, 1992, and June 10, 1997, we enrolled 52 patients. The mean delivered dose-intensity for doxorubicin was 18.6 mg/m(2)/wk. Hospitalization was required in 6% of patients for reversible febrile neutropenia. There were no acute treatment-related deaths, but one patient subsequently died of acute leukemia with a characteristic translocation for anthracycline-related exposure. At 5 years, the event-free survival was 86% for all patients (95% confidence interval, 75% to 95%). CONCLUSION: Continuous dose-dense chemotherapy with G-CSF support produced encouraging results, which seem to be superior to those expected with "standard" doxorubicin and cyclophosphamide chemotherapy. It deserves a test in the form of a randomized trial where this approach to anthracycline-based treatment is compared with intermittent administration.
RCT Entities:
PURPOSE: Theoretical considerations and clinical experience suggest that dose-dense chemotherapy may be superior to other approaches using the same drugs. We studied a dose-dense combination of doxorubicin and cyclophosphamide, with or without fluorouracil, as adjuvant therapy. PATIENTS AND METHODS: Patients with resected breast cancer were treated if they were node-positive and estrogen receptor-negative, positive for overexpression of Her-2-neu, or had four or more involved nodes. Doxorubicin was given weekly to a total dose of 480 mg/m(2). Cyclophosphamide 60 mg/m(2) was given daily by mouth during the period of doxorubicin treatment. The first 30 patients received fluorouracil at 300 mg/m(2)/wk intravenously concurrently with doxorubicin administration. In the last 22, it was omitted because of symptomatic hand-foot syndrome in the majority of patients. Filgrastim (granulocyte colony-stimulating factor [G-CSF]) was administered during chemotherapy every day except the day of intravenous administration and continued until 1 week after the completion of the chemotherapy. RESULTS: Between October 20, 1992, and June 10, 1997, we enrolled 52 patients. The mean delivered dose-intensity for doxorubicin was 18.6 mg/m(2)/wk. Hospitalization was required in 6% of patients for reversible febrile neutropenia. There were no acute treatment-related deaths, but one patient subsequently died of acute leukemia with a characteristic translocation for anthracycline-related exposure. At 5 years, the event-free survival was 86% for all patients (95% confidence interval, 75% to 95%). CONCLUSION: Continuous dose-dense chemotherapy with G-CSF support produced encouraging results, which seem to be superior to those expected with "standard" doxorubicin and cyclophosphamide chemotherapy. It deserves a test in the form of a randomized trial where this approach to anthracycline-based treatment is compared with intermittent administration.
Authors: Matthias Schwenkglenks; Christian Jackisch; Manuel Constenla; Joseph N Kerger; Robert Paridaens; Leo Auerbach; André Bosly; Ruth Pettengell; Thomas D Szucs; Robert Leonard Journal: Support Care Cancer Date: 2006-04-19 Impact factor: 3.603
Authors: Georgiana K Ellis; William E Barlow; Julie R Gralow; Gabriel N Hortobagyi; Christy A Russell; Melanie E Royce; Edith A Perez; Danika Lew; Robert B Livingston Journal: J Clin Oncol Date: 2011-01-10 Impact factor: 44.544
Authors: George T Budd; William E Barlow; Halle C F Moore; Timothy J Hobday; James A Stewart; Claudine Isaacs; Muhammad Salim; Jonathan K Cho; Kristine J Rinn; Kathy S Albain; Helen K Chew; Gary V Burton; Timothy D Moore; Gordan Srkalovic; Bradley A McGregor; Lawrence E Flaherty; Robert B Livingston; Danika L Lew; Julie R Gralow; Gabriel N Hortobagyi Journal: J Clin Oncol Date: 2014-11-24 Impact factor: 44.544
Authors: Jeffrey A Jones; Elenir B C Avritscher; Catherine D Cooksley; Marisol Michelet; B Nebiyou Bekele; Linda S Elting Journal: Support Care Cancer Date: 2006-04-07 Impact factor: 3.603
Authors: Robert K Doot; Lisa K Dunnwald; Erin K Schubert; Mark Muzi; Lanell M Peterson; Paul E Kinahan; Brenda F Kurland; David A Mankoff Journal: J Nucl Med Date: 2007-05-15 Impact factor: 10.057
Authors: Lynn Symonds; Isaac Jenkins; Hannah M Linden; Brenda Kurland; Julie R Gralow; Vijayakrishna V K Gadi; Georgiana K Ellis; Qian Wu; Eve Rodler; Pavani Chalasani; Xiaoyu Chai; Jinny Riedel; Alison Stopeck; Ursa Brown-Glaberman; Jennifer M Specht Journal: Clin Breast Cancer Date: 2021-05-24 Impact factor: 3.225