Trial Information

A Multicenter, Randomized, Cross-over Phase 3 Comparing Preventive Pegylated Filgrastim and Filgrastim in Cancer Patients Receiving Myelosuppressive Chemotherapy

This was a multicenter, randomized, open-label, cross-over, noninferiority study to evaluate
whether a single injection of pegfilgrastim is as effective and safe as daily injections of
filgrastim in patients receiving commonly used chemotherapy regimens. Patients were randomly
assigned in a 1:1 ratio to AOB and BOA arm with center as the stratification variables. All
the patients received two cycles of chemotherapy of identical regimen and dosage. In arm
AOB, patients were administered pegylated filgrastim 100 ug/kg in cycle 1 and filgrastim 5
ug/kg/d in cycle 2; while in arm BOA, patients received filgrastim 5 ug/kg/d in cycle 1 and
pegylated filgrastim 100 ug/kg in cycle 2.

Study drugs Both filgrastim and pegylated filgrastim were provided by GeneLeuk
Biopharmaceutical Co., Ltd, Shandong, China.

In cycle 1 of AOB arm and cycle 2 of BOA arm, on 9 am of day 3, patients were to receive a
dose of 100µg/kg of pegylated filgrastim, based on actual body weight, as a single s.c.
injection.

In cycle 2 of AOB arm and cycle 1 of BOA arm, patients were to receive daily s.c. injection
of filgrastim at a dose of 5 µg/kg/day. Injections began on 9 am of day 3 and continued
daily until an absolute neutrophil count (ANC) ≥10.0 × 109 /l was documented after the
expected nadir or for a maximum of 14 days, whichever occurred first.

Chemotherapy Treatment All cytotoxic agents were administrated on day 1 of the 21-day
regimens. The regimens include PC(paclitaxel 175 mg/m2; carboplatin area under curve[AUC]
5～6 or cisplatin 75 mg/m2 )； AC (doxorubicin [or pirarubicin]60 mg/m2 or epirubicin 100
mg/m2；cyclophosphamide 600 mg/m2), PA(paclitaxel 175 mg/m2 ；doxorubicin [or pirarubicin]50
mg/m2 or epirubicin 80 mg/m2）； CHOP (cyclophosphamide 750mg/m2；doxorubicin[or pirarubicin]
50 mg/m2 or epirubicin100 mg/m2；vincristine1.4 mg/m2；prednisone 100mg，po，day 1-5)。 Efficacy
measurements Blood samples were collected for complete blood counts (cbc) with differential
on days 0, 3, 5, 7, 9, 11, 13, 17 and 21 of each cycle. Day 0 was defined as the day before
day one, in cycle 1 it is the base line, and in cycle 2 is day 21 of cycle 1.

The primary efficacy end point was protective rate of grade 4 neutropenia after chemotherapy
(defined as the rate of ANC keeps above 0.5 × 109 /l through the whole cycle). The secondary
efficacy end points included the rate of grade 3/4 neutropenia, time to neutrophil recovery
(defined as the time from chemotherapy administration until the patient's ANC increased to
2.0 × 109/l after the expected nadir), incidence of febrile neutropenia (defined as
ANC<0.5×109/L and auxiliary temperature>38.0℃), incidence of antibiotic administration and
ANC profile.

Safety assessments Patients recorded their auxiliary temperature daily, and were monitored
for adverse events throughout the study. Before chemotherapy and in the third week of each
chemotherapy cycle, serum hepatic and renal function, electrolysis, urine routine test and
electrocardiograph were examined.

The safety endpoint of this study was incidence and severity of adverse events (WHO grade
1-4), side effects, and changes in clinical laboratory values.