Use of hematopoietic colony-stimulating factors (CSFs) following
induction and consolidation chemotherapy for elderly patients with
acute myeloid leukemia (AML) is a controversial area. Studies have
shown that CSFs can decrease the likelihood and/or shorten the
duration of therapy-related neutropenic complications when given
following induction chemotherapy.[1-7]
The two CSFs, granulocyte colony-stimulating factor (G-CSF,
filgrastim, Neupogen) and granulocyte macrophage colony-stimulating
factor (GM-CSF, sargramostim, Leukine, Prokine), recently received
FDA approval for use as adjunctive therapy in leukemia patients.
However, the high cost of CSFs and the potential stimulation of
leukemic cells in AML patients have raised concerns about their use
in this setting.
In 1994, the American Society of Clinical Oncology (ASCO) published
guidelines stating that caution was recommended for the use of CSFs
in patients with AML due to lack of evidence supporting beneficial
effects on clinical endpoints such as duration of hospitalization,
incidence of severe infection, complete response rates, and survival,
as well as concerns over leukemic stimulation.
In 1996, based on the results from six clinical trials of CSF use for
patients with myeloid leukemias reported between 1994 and 1995, ASCO
guidelines for the use of CSFs in patients with AML were revised.
The new guidelines suggested that primary administration of a CSF
could be used after completion of induction chemotherapy in patients
55 years of age or older.
In 1997, the ASCO Health Services Committee surveyed the ASCO
membership to assess patterns of CSF use for elderly AML patients
following the publication of the revised ASCO CSF guidelines. The
preliminary results were presented (by CLB) at the 1998 ASCO annual
meeting at the podium session on health outcomes.
The survey, accompanied by a cover letter explaining that responses
would be used to evaluate the impact of the ASCO guidelines, was
mailed to a random sample of 1,500 American oncologists and
hematologists who practice medical oncology.
Survey recipients were asked the extent to which they preferred to
administer CSFs to prevent or treat neutropenic complications
associated with induction or consolidation chemotherapy in older AML
patients (Table 1).
Other questions focused on the respondents sociodemographics,
specifically their medical specialty (oncology, hematology, or
hematology/oncology); date of medical school graduation; medical
practice setting (fee-for-service, academic, or HMO); number of years
in practice (less than or more than 3 years); and average weekly new
cancer patient volumes (more than five new cancer patients or less
than five new cancer patients).
The response rate for the 1997 survey was 60.2%. Over half of the
responding physicians practiced in fee-for-service settings, a third
in academic settings, and 14% in HMO settings. Almost a quarter of
the respondents either worked with formal CSF guidelines or practiced
in a setting where guidelines were perceived as influential.
The survey showed a split among physicians in their support for CSF
use following induction chemotherapy, with 40.4% of physicians saying
they "always" or "usually" used a CSF following
induction chemotherapy and 42.2% saying they "rarely" or
"never" used a CSF in the same clinical scenario.
There was more support for CSF use during consolidation chemotherapy,
with 48.5% saying they "always" or "usually"
supported such use vs 32.2% saying they "rarely" or
"never" used CSFs in this setting (P < .05).
Timing of CSF
Of the respondents supporting CSF use following induction
chemotherapy, 42.97% said they favored administration of CSF within
24 hours of completing chemotherapy; 35.72% after reviewing a bone
marrow biopsy demonstrating marrow aplasia; 7.6% as soon as the
patient became neutropenic; and 13.7% when the patient became both
neutropenic and febrile.
The survey showed that physicians practicing in fee-for-service
settings were more likely to prefer CSF use (P = .003) than
physicians practicing in academic settings or HMO settings (Table
Physician specialty was another significant factor associated with
variations in CSF use. Specialists in hematology or
hematology/oncology were more likely to have a stronger preference
for CSF administration than physicians practicing only oncology.
Debate continues to surround the use of CSFs following induction and
consolidation chemotherapy. Support for its administration in elderly
patients with AML was modest at best in the 1996 ASCO CSF
evidence-based guidelines. This uncertainty was reflected by the
survey, which showed that 40% of physicians support CSF use following
induction chemotherapy, while an equal percentage do not. Thus,
physicians appear to be divided as to whether or not CSF for elderly
patients with AML is appropriate.
Of note was the finding of greater support for CSF use in the setting
of AML by hematologists (vs oncologists). However, this finding may
be due to the greater likelihood that specialists in
hematology/oncology are more familiar with recent publications
supporting CSF use following induction chemotherapy.
In addition, physicians practicing in fee-for-service type settings
had a greater propensity for using CSFs in AML than did those in
academic settings or in HMOs. This is similar to findings reported
previously for other clinical situations (ie, for solid tumors and
lymphomas). This finding reflects the restrictions placed on CSF
use in the academic and HMO settings, as well as the tendency in both
settings to follow proprietary guidelines that actively support dose
reduction as the first option for secondary prophylaxis against
febrile neutropenic complications.
Updated CSF practice guideline efforts are underway, and a repeat
ASCO survey of physician use of CSFs is planned. It will be of
interest to see if physician support for CSF use increases or
decreases over time in the setting of AML in older patients.
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