Dose-dense anthracycline-based chemotherapy for node-positive breast cancer.
OBJECTIVE
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.


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%).


CONCLUSIONS
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.
Ellis
Georgiana K
GK
Division of Medical Oncology, University of Washington, and Fred Hutchinson Cancer Research, Seattle, WA. gellis@u.washington.edu
Livingston
Robert B
RB
Gralow
Julie R
JR
Green
Stephanie J
SJ
Thompson
Tove
T
D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015996:Survival Rate; D014481:United States / Q000453:epidemiology
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil