Journal of Clinical Oncology, Vol 16, 3874-3879, Copyright © 1998 by American Society of Clinical Oncology
Low-dose versus standard-dose lenograstim prophylaxis after chemotherapy: a randomized, crossover comparison
GC Toner, JD Shapiro, CR Laidlaw, D Rischin, MJ Millward, M Wolf, H Januszewicz, SV Mitchell, AC Curran, JP Matthews and JF Bishop
Division of Haematology and Medical Oncology, Peter MacCallum Cancer Institute, Melbourne, VIC, Australia.
PURPOSE: Granulocyte colony-stimulating factor (G-CSF) administered
prophylactically after chemotherapy reduces the duration and severity of
neutropenia. This randomized crossover study was designed to assess whether
a lower dose of G-CSF is as effective as a standard dose of 5 microg/kg
daily. PATIENTS AND METHODS: Patients who received standard- dose
chemotherapy regimens expected to cause neutropenia received G-CSF
(lenograstim) that started the day after chemotherapy for 14 days or until
the absolute neutrophil count (ANC) recovered to greater than 10 x 10(9)/L.
The lenograstim dose was randomly allocated to be 2 or 5 microg/kg daily in
the first cycle of chemotherapy and crossed over to the alternate dose for
the second cycle. The study was designed to accrue 40 assessable patients
to provide a power of 80% to detect a difference in duration of neutropenia
of 1 day. Fifty-two patients were randomized to treatment and 43 patients
completed two cycles of identical chemotherapy. RESULTS: There was little
neutropenia irrespective of the dose used. Twenty-three patients (53%) had
no grade III or IV neutropenia and 30 patients (70%) had no grade IV
neutropenia. Crossover trial methodology was used to assess the difference
in outcome caused by the lower dose compared with the standard dose
(estimated treatment effect). There was no significant difference in the
measures of neutropenia, hospitalization, or other clinical outcomes. The
95% confidence interval (one-sided) for the additional duration of
neutropenia caused by the lower dose of lenograstim was 0.43 days or less
for grade III or IV neutropenia and 0.34 days or less for grade IV
neutropenia. CONCLUSION: Lenograstim 2 microg/kg provides similar
protection to 5 microg/kg against neutropenia that complicates
standard-dose chemotherapy. The use of a lower dose has important
implications for the cost-effectiveness of prophylactic G-CSF therapy.
