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.

Prevention of Chemotherapy-Induced Neutropenia with Pegfilgrastim: Pharmacokinetics and Patient Outcomes

“…Similarly, a phase 2 study of pediatric sarcoma patients showed that the safety and efficacy of pegfilgrastim 100 µg/kg was comparable to daily injections of filgrastim 5 µg/kg [63]. Pharmacokinetic profiles in pediatric patients were consistent with those in adult patients [63]. …”

“…Subsequently, a phase 3 noninferiority study in breast cancer patients demonstrated that a single injection of pegfilgrastim 100 µg/kg per cycle was as safe and effective as multiple daily injections of filgrastim 5 µg/kg per cycle for reducing neutropenia and its complications [62]. Similarly, a phase 2 study of pediatric sarcoma patients showed that the safety and efficacy of pegfilgrastim 100 µg/kg was comparable to daily injections of filgrastim 5 µg/kg [63]. Pharmacokinetic profiles in pediatric patients were consistent with those in adult patients [63].…”

Risk assessment of radio-chemotherapy in pediatric soft tissue sarcomas

“…Dose-intensive CTH has become routine for the treatment of most pediatric sarcomas because CTH dose-intensity correlates with tumor response and outcome. Neutropenia is a common toxicity of these regimens (Ferrari et al, 2005;Grier J o u r n a l o f R a d i a t i o n R e s e a r c h a n d A p p l i e d S c i e n c e s 8 ( 2 0 1 5 ) 1 1 0 e1 1 9 et al, 2003;Spunt et al, 2010). Both the depth of the neutrophil nadir and duration of severe neutropenia influence the development of infectious complications.…”

“…Both the depth of the neutrophil nadir and duration of severe neutropenia influence the development of infectious complications. Therefore, preventing or shortening the duration of neutropenia following CTH may facilitate dose-intensity, improve safety, and control costs (Spunt et al, 2010). In the current study, Hematological toxicity was seen in all patients, 71.7% of them were neutropenic and develop febrile neutropenia (FN).…”

The Clinical Pharmacology of Filgrastim and Pegfilgrastim

“…The efficacy, safety, and PK of a single 100-mg/kg subcutaneous dose of pegfilgrastim have been evaluated and compared to 5 mg/kg subcutaneous daily filgrastim in pediatric patients receiving myelosuppressive chemotherapy for sarcoma [49]. The maximum median pegfilgrastim concentration was achieved approximately 1-2 days after pegfilgrastim administration and was sustained until the ANC nadir was reached.…”