Granulocyte-colony-stimulating factor (filgrastim) may overcome imatinib-induced neutropenia in patients with chronic-phase chronic myelogenous leukemia.
BACKGROUND
Imatinib mesylate administration has become standard treatment for patients with chronic myelogenous leukemia (CML). Although the safety profile of imatinib is favorable, Grade > or = 3 neutropenia (according to the National Cancer Institute Common Toxicity Criteria) occurs in 35-45% of patients with CML in chronic phase who receive standard-dose imatinib. Myelosuppression results in treatment interruptions, which may compromise responses to imatinib. The authors investigated the ability of granulocyte-colony-stimulating factor (filgrastim) to reverse imatinib-associated neutropenia, thereby allowing for more continuous imatinib administration.


METHODS
Thirteen patients with chronic-phase CML and Grade > or = 3, imatinib-induced neutropenia were treated with filgrastim. Treatment with filgrastim was initiated after a median of 22 months from the start of imatinib. Eleven patients received filgrastim 5 microg/kg 1-3 times weekly, and 2 patients received filgrastim 5 microg/kg daily; doses were titrated to maintain an absolute neutrophil count (ANC) > or = 10(9)/L.


RESULTS
Seven of 11 patients (64%) who began treatment with an ANC < 1.5 x 10(9)/L had responses (i.e., their ANC improved to > or = 2 x 10(9)/L within 21 days); the other 4 patients experienced slower recovery but were able to continue receiving imatinib uninterrupted. Before filgrastim administration was initiated, patients did not receive imatinib (due to neutropenia-related treatment interruptions) for an average of 21% of the total time since the start of imatinib. This figure decreased to 6% after the start of filgrastim treatment (P = 0.0008). Before filgrastim treatment was initiated, only one patient had achieved a major (partial) cytogenetic response. After the start of filgrastim treatment, five patients had major cytogenetic responses (including two complete responses).


CONCLUSIONS
The authors concluded that filgrastim may overcome imatinib-associated neutropenia and allow improved delivery of imatinib. Some patients may experience improvements in their responses to therapy as a result.
Quintas-Cardama
Alfonso
A
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Kantarjian
Hagop
H
O'Brien
Susan
S
Garcia-Manero
Guillermo
G
Rios
Mary B
MB
Talpaz
Moshe
M
Cortes
Jorge
J
D000328:Adult; D000368:Aged; D001549:Benzamides; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D000068877:Imatinib Mesylate; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy*; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced*; D010865:Pilot Projects; D010879:Piperazines / Q000009:adverse effects*; D011743:Pyrimidines / Q000009:adverse effects*; D011994:Recombinant Proteins
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000068877:Imatinib Mesylate; D000069585:Filgrastim