Abstract
Pegfilgrastim (pegylated granulocyte colony-stimulating factor, PEG-G-CSF) is commonly used as prophylaxis for febrile neutropenia (FN) in high-risk chemotherapy regimens for breast cancer. However, the optimal timing of PEG-G-CSF injections has not been established, despite several investigations into the subject. In this study, patients received epirubicin-based breast cancer chemotherapy and underwent routine blood tests on days seven or eight of initial chemotherapy to assess the risk of FN. Four patients experienced significant decreases in white blood cell (WBC) and neutrophil (NE) counts. To maintain patient safety and relative dose intensity (RDI), the dose was reduced in the second cycle, and PEG-G-CSF administration was moved from day three to day four, as administering PEG-G-CSF within 24 hours to prevent FN is thought to be ineffective. This theory is based on the fact that the WBC and NE expanded by PEG-G-CSF were killed by the remaining chemotherapy. Therefore, we hypothesized that in the next second cycle, administering PEG-G-CSF one day later (day four) after chemotherapy might be effective for these patients. Furthermore, for patients whose blood tests on days seven or eight of the second cycle showed an increase in WBC and NE counts, the chemotherapy dose was increased in the third cycle. Patients with breast cancer (age range: 41-71 years) were assigned to receive PEG-G-CSF on day three or four of a three-week epirubicin and cyclophosphamide-based chemotherapy regimen (dose-dense epirubicin and cyclophosphamide; 5-fluorouracil, epirubicin, and cyclophosphamide; or basic epirubicin and cyclophosphamide) using heterochronic timing. We then compared WBC and NE counts in the same individuals over time. In all four cases, WBC and NE counts on day seven or eight were much greater with PEG-G-CSF injection on day four than with injection on day three. As per heterochronic follow-up, which has not been reported previously, day four injection of PEG-G-CSF appears more effective than day three injection for preventing neutropenia. However, due to the small number of cases in this series and the confounding factor of the chemotherapy dose in the third cycle being approximately 8% less than that in the first cycle in Case 2, it is difficult to generalize our findings. Hence, future studies with a longitudinal follow-up involving a larger number of cases are required.