SAN ANTONIOProphylactic pegfilgrastim (Neulasta) for
patients undergoing myelosuppressive chemotherapy should be used at lower
levels of febrile neutropenia risk than are currently recommended by
guidelines, according to Charles L. Vogel, MD, medical director, Cancer
Research Network, Inc., Plantation, Florida. Dr. Vogel based this conclusion on
clinical trial findings presented at the 27th Annual San Antonio Breast Cancer
Symposium (abstract 5044).
Pivotal filgrastim (Neupogen) and pegfilgrastim studies were
conducted with highly myelosuppressive regimens associated with febrile
neutropenia rates of 60% and 40%, respectively, and demonstrated substantial
reductions. "While ASCO guidelines recommend reserving prophylactic growth
factors for regimens producing febrile neutropenia rates of about 40%, many
oncologists, myself included, feel that having 40% of patients hospitalized
with infections is too high," Dr. Vogel said in an interview. Data suggesting
clinical benefit, and, by inference, avoidance of the cost of hospitalization
and intravenous antibiotics, could help justify expanded pegfilgrastim use.
In this randomized, double-blind study, supported by Amgen,
breast cancer patients received docetaxel (Taxotere) 100 mg/m2 every
3 weeks, a regimen with a predicted febrile neutropenia rate of about 20%. The
hypothesis was that first and subsequent cycle pegfilgrastim use would
significantly reduce febrile neutropenia. The investigators also planned to
look at the timing of neutropenic events.
Patients were randomized to receive pegfilgrastim 6 mg (n =
463) or placebo (n = 465) on day 2 of the first cycle and then through up to
four cycles of docetaxel with or without open-label pegfilgrastim. Febrile
neutropenia was defined as temperature of 38.2° C or higher and absolute
neutrophil count (ANC) of less than 0.5 × 109/L (measured within 1
day after documented fever). Mean age of the patients was 52 years; 62% of
patients had metastatic disease.
Reductions in febrile neutropenia and related
hospitalizations and intravenous anti-infective use were significant. The
febrile neutropenia rate was 17% in the placebo group vs 1% in the
pegfilgrastim group (P < .0001). Hospitalizations due to febrile
neutropenia were required in 14% of the placebo group vs 1% of the
pegfilgrastim group (P < .0001). In addition, intravenous anti-infective
use due to febrile neutropenia was 10% with placebo vs 2% with pegfilgrastim.
Most cases of febrile neutropenia (65%) occurred in the
first cycle, as did 65% of related hospitalizations and 60% of related
intravenous anti-infective use. Grade 3-4 neutropenia was markedly reduced for
patients receiving pegfilgrastim across all cycles. "You can almost entirely
abrogate the febrile neutropenia problem associated with docetaxel at 100 mg/m2,"
Dr. Vogel commented.
Pegfilgrastim was well tolerated, and adverse events were
similar in both groups. While bone pain was somewhat more common in the
pegfilgrastim group (31% vs 27%), Dr. Vogel noted that it was difficult to
"tease out" pegfilgrastim-induced bone pain from bone-metastasis-induced pain.
From these data, the investigators estimated that there was approximately a 5%
incidence of pegfilgrastim-induced bone pain. [The complete study results have
beeen published in the Journal of Clinical Oncology (23:1178-1184,
"I think these data are pretty convincing and can be
generalized to any comparable regimen. Many breast cancer and other cancer
regimens are in this 20% range," Dr. Vogel said. "I would like to see the
guidelines changed to 20%. That would be far more reasonable than 40%." He said
that a prospective cost-effectiveness study needs to be conducted.