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.
A single-site setting in Germany
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.