THOUSAND OAKS, California—The US Food and Drug Administration has approved
Amgen’s Neulasta (pegfilgrastim), its pegylated granulocyte
colony-stimulating factor (G-CSF) that is administered as a single fixed dose
per chemotherapy cycle, the company said in a news release. Neulasta is
indicated for decreasing the incidence of infection, as manifested by febrile
neutropenia, in patients with nonmyeloid malignancies receiving
myelosuppressive anticancer drugs associated with a clinically significant
incidence of febrile neutropenia.

Until now, filgrastim (G-CSF, Neupogen), also an Amgen product, was the
only agent approved for this use. However, the burden of daily dosing
(sometimes for as many as 14 consecutive days) has led many health care
professionals to wait to intervene with filgrastim until after a chemotherapy
patient developed a neutropenic infection, the company said in a news release.

With Neulasta, a polyethylene glycol molecule, or PEG unit, is added to
enlarge the filgrastim molecule, thereby extending its half-life and causing it
to be removed more slowly from the body. This allows for administration in a
single dose per chemotherapy cycle.

Self-regulation (neutrophil-mediated clearance) of Neulasta allows the drug
to remain in the blood throughout the time during which a patient is
neutropenic and then be cleared rapidly when it is no longer needed (as
neutrophils recover toward normal levels). "The less frequent dosing of
Neulasta means that patients will require fewer painful injections, fewer
office visits for those injections, and fewer disruptions to their lives at a
time when they are overwhelmed with a serious disease," said Frankie Ann
Holmes, MD, a lead clinical trial investigator and associate director of
research at US Oncology, Houston.

Data from two pivotal phase III studies in breast cancer patients
demonstrated that a single dose of Neulasta provided protection from infection
comparable to a mean of 11 daily injections of filgrastim (5 µg/kg/d),
reducing both the duration of severe neutropenia and the frequency of
neutropenia with fever.

The randomized, double-blind trials were conducted in breast cancer patients
undergoing up to four cycles of chemotherapy with doxorubicin and docetaxel (Taxotere).
In one study of 310 patients, the Neulasta dose was 100 µg/kg and in the other
study (n = 157), a fixed 6-mg Neulasta dose was given.

Days of severe neutropenia were comparable between treatment groups in all
cycles. The mean duration of severe neutropenia in cycle 1 appeared to be no
different for patients in the Neulasta and filgrastim groups: an average of 1.8
days vs 1.6 days, respectively, in the fixed-dose trial, and 1.7 days vs 1.6
days in the by-weight dosing trial. Neulasta was comparable to filgrastim with
respect to rates of febrile neutropenia across all chemotherapy cycles in both
studies.