Spunt, S.L., Irving, H., Frost, J., Sender, L., Guo, M., Yang, B.B., . . . Santana, V.M. (2010). Phase II, randomized, open-label study of pegfilgrastim-supported VDC/IE chemotherapy in pediatric sarcoma patients. Journal of Clinical Oncology, 28, 1329–1336.

The purpose of this article is to evaluate the safety, clinical response, and pharmacokinetics of pegfilgrastim compared to filgrastim in pediatric patients with sarcoma receiving dose-intensive vincristine-doxorubicin-cyclophosphamide/ifosfamide-etoposide (VDC/IE) chemotherapy.

Pediatric patients with biopsy-proven sarcomas scheduled to receive four cycles of VDC (cycles 1 and 3) / IE (cycles 2 and 4) chemotherapy in three-week intervals were randomized in a 6:1 ratio (pegfilgrastim to filgrastim). Pegfilgrastim group received one subcutaneous injection of 100 mcg/kg and filgrastim group received daily subcutaneous injections 5 mg/kg daily. Both groups received injections starting about 24 hours after completion of week 1 chemotherapy with continuation until a post-nadir absolute neutrophil count (ANC) greater than 10 x 10⁹/L achieved or until 24 hours prior to the next chemotherapy cycle. ANC greater than 1 x 10⁹/L and platelets greater than 100 x 10⁹/L were the minimum acceptable levels for chemotherapy. Chemotherapy modifications were made for infections requiring intensive care or for typhlitis, meningitis, or O₂-dependent pneumonia.

• 35 patients were in the sample.
• The age range was 0–21 years.
• 36.4% of the sample were female, 63.6% were male
• Diagnoses were ewing sarcoma family, rhabdomyosarcoma, and other soft-tissue sarcoma.
• 35 patients were White; 3 were Black, 5 were Hispanic, and  one was classified as Other.

10 outpatient settings in the United States and Australia

• The phase of care was active treatment
• Applications was for pediatrics

Phase II randomized, controlled trial (RCT), open-label.

• Duration of grade 4 neutropenia (ANC of 0.5 x 10⁹/L or lower) during cycles 1 and 3.
• Time to ANC recovery to 0.5 x 10⁹/L or greater in cycles 1 and 3
• Rate of febrile neutropenia (defined as ANC less than 0.5 x 10⁹/L) and an oral or oral-equivalent temperature of 38.2°C or greater on the same day.
   

85% of patients in the filgrastim group had febrile neutropenia compared to 68% in the pegfilgrastim group. The duration of grade 4 neutropenia was about equal in both groups with a median duration of 1 day less in the pegfilgrastim group during cycle 1. The median recovery to ANC time was also the same in both groups. One patient in the pegfilgrastim group in cycle 1 and three in cycle 3 failed to have neutrophil recovery. All patients in the filgrastim group had neutrophil recovery. The pharmacokinetics were similar for pegfilgrastim and filgrastim. In the pegfilgrastim group, duration of grade 4 neutropenia was inversely related to age (i.e., the younger the patient, the longer the duration). Adverse events were statistically equivalent between the groups; however, more types of events occurred in the pegfilgrastim group.

The use of pegfilgrastim is as safe and effective to use as filgrastim in pediatric patients with sarcomas and requires just one dose compared to daily doses of filgrastim.

• Small sample (less than 100)
• No blinding with risk of bias
• The 6:1 ratio of patients receiving pegfilgrastim versus filgrastim makes the comparisons between groups more challenging in determining the efficacy of outcomes.
   

The administration of pegfilgratim as a one-time dose can be as effective as daily doses of filgrastim against neutropenia in pediatric patients being treated with myelosuppressive chemotherapy for sarcomas. Nurses can advocate for the use of pefgilgrastim to decrease the burden of number of injections in pediatric patients with sarcomas.