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.