Holmes, F.A., Jones, S.E., O'Shaughnessy, J., Vukelja, S., George, T., Savin, M., . . . Liang, B.C. (2002). Comparable efficacy and safety profiles of once-per-cycle pegfilgrastim and daily injection filgrastim in chemotherapy-induced neutropenia: A multicenter dose-finding study in women with breast cancer. Annals of Oncology, 13, 903–909.
The purpose of the study was to investigate the efficacy, safety, and pharmacokinetics of various single doses of pegfilgrastim per chemotherapy cycle in women receiving chemotherapy with doxorubicin and docetaxel.
On day 2 of each chemotherapy cycle, 24 hours after chemotherapy completion, patients either received a single subcutaneous injection of pegfilgrastim or began daily injections of filgrastim for 14 days or until absolute neutrophil count (ANC) recovery to 10 x 109/L after nadir. Within the pegfilgrastim group, patients received 30, 60 or 100 mcg/kg. Filgastrim was given at 5 mcg/kg per day. Patients were randomly assigned to treatment group. Treatment was repeated for each cycle, up to four cycles. Blood samples were collected at screening, before each chemotherapy cycle, and once weekly during cycle 1. Findings were evaluated regarding duration of grade 4 neutropenia and rates of febrile neutropenia.
Multiple sites in the United States
Active antitumor treatment
Randomized dose finding phase II. Analysis also included open-label phase data.
Mean duration of grade 4 neutropenia in patients on filgastrim during cycle 1 was 2.5, and was 2.0 in patients receiving 30 mcg/kg pegfilgastrim (95% CI [0.35,1.93]). There was not a statistically significant difference in cycle 1 with the other pegfilgastrim dosage groups. Mean time to ANC recovery for cycle 1 was 9.4 days with filgastrim, 9.5 with 100 mcg pegfilgastrim (p = 0.05), 10.3 with 60 mcg (p = 0.05) pegfilgastrim, and 11 with 30 mcg doses (not significant). There were no significant differences across groups in any other outcome measure. There were no significant differences in adverse events. A single dose of pegilfrastim produced a sustained serum concentration, with maximum concentration at about 24 hours, and was sustained until ANC nadir.
Pegfilgastrim at a single dose per chemotherapy cycle was similar to daily filgastrim in efficacy and adverse effects.
Findings suggest that single dose of pegfilgastrim per chemotherapy cycle is similar to daily filgastrim dosing in terms of safety and efficacy. The need for fewer subcutaneous injections with single dosing may be beneficial to patients.