Loibl, S., Mueller, V., von Minckwitz, G., Conrad, B., Koehne, C.H., Kremers, S., . . . GBG/AGO/NOGGO study groups. (2011). Comparison of pegfilgrastim on day 2 vs. day 4 as primary prophylaxis of intense dose-dense chemotherapy in patients with node-positive primary breast cancer within the prospective, multi-center GAIN study (GBG 33). Supportive Care in Cancer, 19, 1789–1795.

The purpose of the study was to examine the superiority in reducing grade 4 leucopenia of pegfilgrastim given on day 4 over giving pegfilgrastim on day 2.

Patients were randomized to receive pegfilgrastim subcutaneously (6 mg) on day 2 or on day 4 in a 1:1 ratio. All sub study patients received intense dose-dense (IDD) chemotherapy consisting of epirubicin 150 mg/m² every two weeks for three cycles, paclitaxel 225 mg/m² every two weeks for three cycles, and cyclophosphomide 2,000 mg/m² every two weeks for three cycles. All received prophylactic oral quinolone antibiotics.

• 355 patients were randomized to receive pegfilgrastim on day 2 (n = 177) or day 4 (n = 178).  
• The median age was 45 years with a range of 24–69 years.
• 100% of the participants were female.
• Female patients biologically younger than 65 years with histologic confirmed, unilateral, or bilateral node-positive breast carcinoma.   
• Patients were required to have adequate surgical treatment with histologic complete resection (R0) of the tumor and greater or equal 10 axillary nodes with primary wound healing and no signs of infection.
   

A single-site setting in Germany

• The phase of care was active treatment.
• The application was for late effects and survivorship.
   

Randomized two-group trial

GAIN (German Adjuvant Intergroup Node Positive) study toxicity grading

The study failed to demonstrate that pegfilgrastim on day 4 was more efficacious than on day 2 with respect to grade 4 leucopenia. For patients receiving epirubicin overall, 11% of patients receiving day 2 dosing had an episode of grade 4 leucopenia during the first three cycles of chemotherapy, compared to 4% of those receiving CSF on day 4 (p = 0.015). There were no significant differences between groups in chemotherapy dose reductions or delays. During cyclophosphamide, significantly more infections occurred in the day 2 administration group (p = 0.035). Across the entire treatment, there were no differences between groups in febrile neutropenia, infections, and treatment alterations.

This study failed to demonstrate that administering pegfilgrastim on day 4 was more efficacious than on day 2 with respect to grade 4 leucopenia (the primary endpoint), febrile neutropenia, or infections.

No blinding
 

The data does not support a change in the current standard dosing schedule; however, it does suggest that administration of colony-stimulating factor on day 4 might be an appropriate alternative to day 2 dosing.