Incidence of Grade 4 Neutropenia During the Nadir Period After the First Cycle of Doxorubicin and Cyclophosphamide Chemotherapy in Patients with Breast Cancer
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Abstract
BACKGROUND: Grade 4 neutropenia is a common hematologic toxicity associated with doxorubicin and cyclophosphamide (AC) chemotherapy. However, the incidence of Grade 4 neutropenia during the nadir period after the first cycle of AC chemotherapy in routine clinical practice in Thailand remains unclear.
OBJECTIVES: This study aimed to determine the incidence of Grade 4 neutropenia during the nadir period after the first cycle of AC chemotherapy and to identify factors associated with Grade 4 neutropenia. Secondary objectives were to describe other hematologic toxicities and subsequent chemotherapy management following the first cycle.
METHODS: This retrospective observational study included patients with breast cancer who received doxorubicin (60 mg/m²) and cyclophosphamide (600 mg/m²) chemotherapy at Pattaya Bhattamakun Hospital between May 2023 and May 2026. Complete blood counts obtained approximately 14 days after the first chemotherapy cycle were reviewed to assess hematologic toxicity during the expected nadir period. No patients received primary prophylactic granulocyte colony-stimulating factor (G-CSF) before the first cycle. Factors associated with Grade 4 neutropenia were evaluated using univariable and multivariable logistic regression analyses.
RESULTS: A total of 138 patients were included. Grade 4 neutropenia occurred in 68 patients, corresponding to an incidence of 49.3% (95% CI, 40.7–57.9%). Overall, neutropenia of any grade occurred in 128 patients (92.8%; 95% CI, 87.1–96.5%). Anemia of any grade occurred in 23 patients (16.7%), and thrombocytopenia occurred in 1 patient (0.7%). No documented febrile neutropenia or neutropenia-related hospitalization was observed. Subsequent chemotherapy dose reduction was required in 13 patients (9.4%), and and G-CSF was administered after chemotherapy in 3 patients (2.2%). In the multivariable analysis, baseline ANC was significantly associated with Grade 4 neutropenia. For every 1,000 cells/µL increase in baseline ANC, the odds of developing Grade 4 neutropenia decreased by 24% (adjusted OR, 0.760; 95% CI, 0.601–0.962; p = 0.022).
CONCLUSIONS: Grade 4 neutropenia occurred in approximately half of patients during the nadir period after the first cycle of AC chemotherapy. Baseline ANC was significantly associated with Grade 4 neutropenia; However, its ability to predict clinically consequential outcomes or guide prophylactic G-CSF use could not be established in this study. Further prospective studies are warranted to validate this association and determine its clinical utility.
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