title: Phase III trial comparing granulocyte colony-stimulating factor to leridistim in the prevention of neutropenic complications in breast cancer patients treated with docetaxel/doxorubicin/cyclophosphamide: results of the BCIRG 004 trial.
abstract: This randomized, double-blind, phase III trial compared granulocyte colony-stimulating factor (G-CSF; filgrastim) and leridistim (formerly myelopoietin), a chimeric dual agonist that binds both G-CSF and interleukin-3 receptors, for the prevention of neutropenic complications in patients with breast cancer receiving TAC (docetaxel/doxorubicin/cyclophosphamide) chemotherapy. Patients with metastatic (44%) or localized breast cancer (56%) were randomized to G-CSF 5 microg/kg subcutaneously (s.c.) daily (n = 135), leridistim 5 microg/kg s.c. daily (n = 139), or leridistim 10 microg/kg s.c. every other day alternating with placebo (n = 139). Following administration of TAC (docetaxel 75 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2) on day 1, patients received growth factor beginning on day 2 until the postnadir absolute neutrophil count exceeded 1500 cells/ microL. Chemotherapy cycles were repeated every 21 days. The incidence of febrile neutropenia was 7% in the G-CSF arm, 19% in the daily leridistim arm (P = 0.003 for comparison with G-CSF) and 22% in the alternate-day leridistim arm (P < 0.001 for comparison with G-CSF). There was no significant difference between treatment arms in the cumulative percentage of patients experiencing grade 4 neutropenia at some point during therapy (85%-88%). However, grade 4 neutropenia occurred in 53% of cycles in the G-CSF cohort, 61% of cycles in the daily leridistim group (P = 0.063 for comparison with G-CSF), and 63% of cycles in the alternate-day leridistim group (P = 0.015 for comparison with G-CSF). We conclude that G-CSF is superior to leridistim in the prevention of febrile neutropenia in patients with advanced breast cancer receiving TAC chemotherapy. The up-front prophylactic use of G-CSF is a reasonable supportive therapy for patients treated with docetaxel/anthracycline-based combination chemotherapy.
authors.affiliation: Cancer Therapy Development Program and Jonsson Comprehensive Cancer Center, University of California-Los Angeles, Peter Ueberroth Building 3360B, 10945 LeConte Avenue, Los Angeles, CA 90095-7077, USA. jean-marc.nabholtz@bcirg.com
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Nabholtz
authors.forename: Jacques
authors.initials: J
authors.lastname: Cantin
authors.forename: Jose
authors.initials: J
authors.lastname: Chang
authors.forename: Raymond
authors.initials: R
authors.lastname: Guevin
authors.forename: Ravi
authors.initials: R
authors.lastname: Patel
authors.forename: Katherine
authors.initials: K
authors.lastname: Tkaczuk
authors.forename: Pavel
authors.initials: P
authors.lastname: Vodvarka
authors.forename: Mary-Ann
authors.initials: MA
authors.lastname: Lindsay
authors.forename: David
authors.initials: D
authors.lastname: Reese
authors.forename: Alessandro
authors.initials: A
authors.lastname: Riva
authors.forename: John
authors.initials: J
authors.lastname: Mackey
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077143:Docetaxel; D004311:Double-Blind Method; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007377:Interleukin-3 / Q000627:therapeutic use*; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control*; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D043823:Taxoids; D016896:Treatment Outcome
chemical_list: D007377:Interleukin-3; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D043823:Taxoids; D016179:Granulocyte Colony-Stimulating Factor; D000077143:Docetaxel; C400711:leridistim; D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel; D000069585:Filgrastim