Phase II, randomized, open-label study of pegfilgrastim-supported VDC/IE chemotherapy in pediatric sarcoma patients

Abstract

This multicenter, randomized, open-label study evaluated the efficacy, safety, and pharmacokinetics of a single subcutaneous pegfilgrastim injection with daily subcutaneous filgrastim administration in pediatric patients receiving myelosuppressive chemotherapy for sarcoma. PATIENTS AND METHODS Forty-four patients with previously untreated, biopsy-proven sarcoma stratified into three age groups (0-5, 6-11, and 12-21 years) were randomly assigned in a 6:1 randomization ratio to receive a single pegfilgrastim dose of 100 microg/kg (n = 38) or daily filgrastim doses of 5 microg/kg (n = 6) after chemotherapy (cycles 1 and 3: vincristine-doxorubicin-cyclophosphamide; cycles 2 and 4: ifosfamide-etoposide). The duration of grade 4 neutropenia, time to neutrophil recovery, incidence of febrile neutropenia, and adverse events were recorded. Results Pegfilgrastim and filgrastim were similar for all efficacy and safety end points, and their pharmacokinetic profiles were consistent with those in adults. Younger children experienced more protracted neutropenia and had higher median pegfilgrastim exposure than older children. CONCLUSION A single dose of pegfilgrastim at 100 microg/kg administered once per chemotherapy cycle is comparable to daily injections of filgrastim at 5 microg/kg for pediatric sarcoma patients receiving myelosuppressive chemotherapy.

Fig 1.

CONSORT diagram. (*) One patient was withdrawn before study drug administration because of concerns about protocol-required blood draws after migration and infiltration of the patient's intravenous catheter. (†) Treatment completion was defined as completing all planned cycles of study drug.

Fig 2.

Study schema. Chemotherapy: Vincristine-doxorubicin-cyclophosphamide (VDC) cycles 1 and 3 (vincristine [V] at 2.0 mg/m² by intravenous [IV] push, days 1, 8, and 15; doxorubicin [D] at 75 mg/m², IV infusion over 48 hours, day 1; cyclophosphamide [C] 1,200 mg/m²/d, days 1 and 2, IV infusion over 1 hour; and mesna at 360 mg/m² in four doses by continuous infusion or bolus at regular intervals). Ifosfamide-etoposide (IE) cycles 2 and 4 (ifosfamide [I] at 1,800 mg/m²/d × 5 days, IV over 1 hour; etoposide [E] at 100 mg/m²/d × 5 days, IV over 1 hour; and mesna at 360 mg/m² in four doses by continuous infusion or bolus at regular intervals). Growth factor: pegfilgrastim at 100 μg/kg subcutaneously [SC] by single injection 24 hours after completion of chemotherapy; filgrastim at 5 μg/kg/d SC daily 24 hours after completion of chemotherapy per package insert until absolute neutrophil count [ANC] recovery (ANC ≥ 10 × 10⁹/L) or 24 hours before the next cycle.

Fig 3.

Pharmacokinetic and absolute neutrophil count (ANC) profiles in cycles 1 and 3. Pegfilgrastim profiles after 100 μg/kg pegfilgrastim administration to patients in the following age groups: (A) 0 to 5 years, (B) 6 to 11 years, and (C) 12 to 21 years. Pharmacokinetic and ANC profiles in patients in the 6 to 11 years age group receiving (D) pegfilgrastim and (E) filgrastim. Conc, concentration. (*) Number of patients beginning cycle 3.