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A comparison of therapeutic schedules for administering granulocyte
colony-stimulating factor to nonhuman primates after high-dose chemotherapy
BR Meisenberg, TA Davis, AJ Melaragno, R Stead and RL Monroy
Hematology/Oncology Division, US Naval Hospital, San Diego.
Granulocyte colony-stimulating factor (G-CSF) has been shown to be
effective in clinical trials for reducing the period of neutropenia after
chemotherapy. In this study, we compared the timing for initiating G-CSF
administration after chemotherapy with the duration of neutropenia and
hematopoietic regeneration. Nonhuman primates treated with high-dose
chemotherapy (mechloroethamine, 1.5 mg/kg, intravenously) and not
administered G-CSF therapy experienced 8 days of neutropenia (absolute
neutrophil count [ANC] less than 1,000/mm3) and had an ANC nadir of 124 +/-
64/mm3 at day 7. Monkeys receiving G-CSF (5 micrograms/kg/d,
subcutaneously) began treatment on either days 1, 3, 5, or 7 after
chemotherapy. Monkeys treated with G-CSF had an earlier ANC recovery and
the number of days with an ANC less than 500/mm3 and ANC less than
1,000/mm3 was reduced by approximately 50% in all treatment strategies. All
G-CSF-treated animals, irrespective of the time that G-CSF was initiated,
reached an ANC of 10,000/mm3 on day 13 +/- 1 day after chemotherapy. These
results demonstrated that the duration of G-CSF therapy was almost twice as
long for monkeys treated on day 1 as it was for monkeys that received
therapy beginning on day 7. A comparison of the results for all treated
monkeys identified a distinct difference in the responses of monkeys
treated on day 1 from that of animals treated with G-CSF at later times.
G-CSF initiated 1 day after chemotherapy led to an earlier onset of
neutropenia and a more rapid and augmented recovery of myeloid progenitor
cells in the peripheral blood when compared with control and delayed
therapy groups. This study demonstrates that neutropenia due to a single
dose of mechloroethamine can be equally reduced with both early and delayed
initiation of G-CSF. Further, initiating G-CSF therapy after 7 days
required approximately 50% less days of therapy to reach an appropriate
termination point. The applicability of these findings to other
chemotherapy regimens and for repeated cycles is uncertain and needs to be
further evaluated. This is a US government work. There are no restrictions
on its use.
Volume 79,
Issue 9,
pp. 2267-2272,
05/01/1992
Copyright © 1992 by The American Society of Hematology
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