Burris, H.A., III, Belani, C.P., Kaufman, P.A., An, G., Schwartzberg, L.S., Paroly, W.S., . . . Saven, A. (2010). Pegfilgrastim on the same day versus next day of chemotherapy in patients with breast cancer, non-small-cell lung cancer, ovarian cancer, and non-Hodgin's lymphoma: Results of four multicancer, double-blind, randomized phase II studies. Journal of Oncology Practice, 6, 133–140.

The purpose of the study was to compare severe neutropenia duration and incidence of febrile neutropenia in patients getting chemotherapy with pegfilgrastim on the same day or 24 hours later.

Four studies were analyzed separately, and data were not compiled for overall analysis across cancer types. In all settings, patients were randomly assigned to either receive pegfilgrastim 6 mg on the last day of the chemotherapy cycle and placebo injection 24 hours later, or placebo on the last day of the cycle and pegfilgrastim 6 mg 24 hours later. Anti-infective prophylaxis was not allowed. Incidence of grade 4 neutropenia was the primary study endpoint, and patients were included and analyzed for one cycle. Complete blood counts were obtained weekly for each chemotherapy cycle.

• 275 participants were included.
• The mean age was 58.6 years.
• Females made up 67.6% of the sample; males made up 32.4%.
• This report is of four studies with the same design, one in breast cancer cases, one in non-Hodgkin lymphoma, one in non-small cell lung cancer, and one in ovarian cancer.
• Disease stages varied
   

• Multi-site (74 sites in the United States) 
• Setting type was not specified  

Active antitumor treatment

Randomized, double-blind placebo controlled

Not stated

In the breast study, grade 4 neutropenia was reported in 93% of same day patients and 78% of next day patients. Mean duration of severe neutropenia was 1.2 days longer in the same day group. In the lymphoma study, severe neutropenia was reported among 86% of same day pegfilgrastim patients and 64% of next day patients. Mean duration of severe neutropenia was 0.9 days longer in the same day group. Incidence of febrile neutropenia was essentially the same in both groups. In the lung cancer group, only 5% of patients experienced severe neutropenia. Analysis of the ovarian group was not done due to study closure prior to obtaining a sufficient sample. Authors report that noninferiority statistical analysis showed that next day pegfilgrastim was not inferior to same day pegilgrastim.

 Findings suggest that different timing of pegfilgrastim administration  within a two day window may not make a difference in incidence of severe neutropenia in these patient groups.

• Risk of bias(sample characteristics)
• Measurement/methods not described  
• Measurement validity/reliability questionable
• The authors note that some of the studies were underpowered to detect significant differences.
• Various samples were highly variable in terms of disease type and stage, and though data were reported by study, no further subgroup analysis was possible. 
• Method of measurement of grade of neutropenia was not described and timing of this determination not stated. 
• In some cases, it appears that analysis was done only in cycle 1 but, in other sections of the report, this is not clear.
• Chemotherapy agents used were not reported, so it is unclear how myelosuppressive they were and potential differences.

This report provides some information from four studies to examine differences in timing of administration of colony-stimulating factors. The most beneficial and cost-effective formulations, dosages, and timing have not been determined. This report has several limitations in study design and results reported.