SAN ANTONIOTargeted support with G-CSF (filgrastim, Neupogen) based on
cycle 1 ANC (absolute neutrophil count) nadirs improves the delivery of
planned-dose-on-time chemotherapy and significantly reduces the incidence of
febrile neutropenia and related hospitalizations, according to study from The
University of Texas M.D. Anderson
Cancer Center study using a prospective risk model. Edgardo Rivera, MD,
assistant professor of breast medical oncology, presented the
results at the 24th San Antonio Breast Cancer Symposium (abstract 3).
Full-dose chemotherapy is associated with prolonged survival, but according
to large multicenter studies, approximately 20% of early breast cancer patients
receive less than 85% of planned doses. Neutropenia is the primary reason for
dose delays and reductions, Dr. Rivera said. Primary prophylaxis with
colony-stimulating factors is an alternative treatment option to chemotherapy
dose modifications. "Filgrastim reduces the risk of hematologic
complications and helps maintain planned doses on schedule; however, filgrastim
support as primary prophylaxis is only offered to 3% of patients," he
Retrospective risk models suggest it is possible to identify patients at
high risk for neutropenic events and target them for filgrastim support. In the
Silber Predictive Risk Model (J Clin Oncol 16:2392-2400, 2435-2444, 1998), the
lower the cycle 1 ANC nadir, the higher the probability of neutropenic events
with subsequent cycles. Silber’s model was retrospectively evaluated using
143 early breast cancer patients at M.D. Anderson. The analysis found that the
first-cycle ANC nadir was the sole significant predictor of neutropenic events
and was associated with reduced chemotherapy doses.
The current study implemented the Silber model in a prospective multicenter
trial of 624 patients with stage I-III breast cancer receiving adjuvant
Adriamycin/cyclophosphamide (AC), cyclophosphamide/methotrexate/fluorouracil (CMF),
cyclophosphamide/Adriamycin/fluorouracil (CAF), or doxorubicin followed by CMF.
The first cycle of chemotherapy was administered without filgrastim support;
then patients were assigned to risk groups based on cycle 1 ANC nadirs.
Patients with a first-cycle ANC nadir of 500/mm³ or less were assigned to the
high-risk group; patients with nadir greater than 500/mm³ were designated low
risk. High-risk patients received filgrastim for all subsequent cycles starting
24 hours after chemotherapy and continuing to ANC of 10,000/mm³ or higher.
Low-risk patients received filgrastim secondary to a febrile neutropenic
episode or a delay due to neutropenia.
The patients were matched with 1,022 historical controls by regimen, disease
stage, age, and baseline ANC.