A Study Comparing Pegylated Filgrastim and Filgrastim in Support for Chemotherapy
Condition: Cancer
Study type: Interventional
Phase: Phase 3

Summary: 
      Neutropenia is one of the most frequent adverse effects of chemotherapy, and the main factor
      to limit the dosage and delay the schedule of chemotherapy. Preventive filgrastim
      administration has long been established as the standard of care. A pegylated filgrastim was
      independently developed by GeneLeuk Biopharmaceutical Co., Ltd, Shandong, China. It composed
      of filgrastim and a 20 kd polyethylene glycol molecule covalently bound at the N-terminal
      residue. Preclinical studies phase 1 and phase 2 trials have shown that pegylated filgrastim
      has decreased renal clearance, increased plasma half-life, and prolonged efficacy in compare
      with ﬁlgrastim. These characters were similar to those of Neulasta.

      The investigators designed a multicenter, randomized, cross-over phase Ⅲ trial to compare the
      efficacy and safety of a single injection of pegylated filgrastim and daily injections of
      ﬁlgrastim in chemotherapy naive patients receiving commonly used regimens. The hypothesis is
      that pegylated filgrastim is similarly effective and safe with regular filgrastim.
    

Detailed description: 
      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.
    

Intervention name(s): pegylated filgrastim and ﬁlgrastim; ﬁlgrastim and pegylated filgrastim
Intervention type(s): Drug; Drug
Intervention description(s): patients were administered pegylated filgrastim 100 ug/kg in cycle 1 and ﬁlgrastim 5 ug/kg/d in cycle 2; patients received ﬁlgrastim 5 ug/kg/d in cycle 1 and pegylated filgrastim 100 ug/kg in cycle 2
Intervention MeSH terms: Lenograstim
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Supportive Care
Keywords: Granulocyte colony-stimulating factor , recombinant; Polyethylene glycols; Neutropenia; Drug therapy, combination