title: Neutrophil-guided dosing of anthracycline-cyclophosphamide-containing chemotherapy in patients with breast cancer: a feasibility study.
abstract: The aim of this study was to investigate whether neutrophil-guided dose escalation of anthracycline-cyclophosphamide-containing chemotherapy (ACC) for breast cancer is feasible, in order to optimize outcome. Breast cancer patients planned for 3-weekly ACC were enrolled in this study. The first treatment cycle was administered in a standard BSA-adjusted dose. The absolute neutrophil count was measured at baseline and at day 8, 11 and 15 after administration of ACC. For patients with none or mild (CTC grade 0-2) neutropenia and no other dose-limiting toxicity, we performed a 10-25 % dose escalation of the second cycle with the opportunity to a further 10-25 % dose escalation of the third cycle. Thirty patients were treated in the adjuvant setting with either FE100C (n = 23) or AC (n = 4), or in the palliative setting with FAC (n = 3). Two out of 23 patients (9 %) treated with FEC did not develop grade 3-4 neutropenia after the first treatment cycle. Dose escalation was performed in these two patients (30 % in one and 15 % in the other patient). During dose escalation, there were no complications like febrile neutropenia. No patients treated with FAC or AC could be escalated, since all of them developed grade 3-4 neutropenia. We conclude that asymptomatic grade 3-4 neutropenia is likely to be achieved in the majority of patients with breast cancer treated with ACC according to presently advocated BSA-based dose levels. Escalation of currently advocated ACC doses without G-CSF, with a target of grade 3-4 neutropenia, is feasible, but only possible in a small proportion of patients. EudraCT 2010-020309-33.
authors.affiliation: Department of Internal Medicine, Ikazia Hospital, PO Box 5009, 3008 AA, Rotterdam, The Netherlands, j.drooger@ikazia.nl.
authors.forename: Jan C
authors.initials: JC
authors.lastname: Drooger
authors.forename: Johanna M
authors.initials: JM
authors.lastname: van Pelt-Sprangers
authors.forename: Corry
authors.initials: C
authors.lastname: Leunis
authors.forename: Agnes
authors.initials: A
authors.lastname: Jager
authors.forename: Felix E
authors.initials: FE
authors.lastname: de Jongh
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D015251:Epirubicin / Q000008:administration & dosage; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D009504:Neutrophils / Q000473:pathology*; D011379:Prognosis; D011446:Prospective Studies
chemical_list: D018943:Anthracyclines; D015251:Epirubicin; D003520:Cyclophosphamide; D005472:Fluorouracil