Early neutropenia on day 8 treated with adjuvant Docetaxel-based chemotherapy in early breast cancer patients: Putative mechanisms within the neutrophil pool system

Abstract

Most chemotherapy regimens cause neutropenic nadirs between days 10 and 14, and administration of granulocyte colony-stimulating factor (G-CSF) support relies on this timing. In docetaxel (DOC)-based chemotherapy, the frequency of febrile neutropenia (FN) and the G-CSF dose administered varied greatly between studies. Our study goal was to forecast the necessary dose of G-CSF by comparing day 8 neutropenia with putative changes within the neutrophil pool. We conducted a retrospective observational analysis of 242 early breast cancer patients who had received adjuvant DOC-based chemotherapy (DOC group) compared with 43 patients who had received FEC chemotherapy (FEC group). Patients who were given a standard dose and had a blood test on day 8 in the 1st cycle were eligible. In the DOC group, patients routinely received prophylactic administration of G-CSF (150 μg/body) on day 3 and received additional G-CSF based on a blood test on day 8. Results of the day 8 blood test showed that severe neutropenia (<500/mm3, average 494/mm3) was observed in 152 out of 242 (62.8%) patients in the DOC group, while in the FEC group (n = 43), neutropenia was ambiguous (average 1,741/mm3). In the FEC group, 9 out of 43 patients (20.9%) and in the DOC group, 27 out of 242 patients (11.1%) experienced FN. In the DOC group, day 8 neutropenia was predictive for FN in a logistic regression model (OR 0.79 [95% CI: 0.655-0.952], p = 0.013). Among 214 patients under 70 years old, the planned chemotherapy cycle was completed in 190 (88.8%) patients who also received the maximum dose of G-CSF (150 μg/body) four times, while 23 patients could not complete the planned chemotherapy cycle, but only five because of FN-related complications. Patients treated with DOC should be treated for primary prophylaxis with G-CSF support at an earlier time starting with a relatively small dose.

Fig 1. Absolute neutrophil count on day 8 in TC, DOC and FEC-treated patients.

Box-plot diagram of absolute neutrophil count on day 8 in TC-treated, DOC-treated and FEC-treated patients.

Fig 2. The first febrile neutropenia in DOC group.

The bars represent the numbers of patients experienced the first occurrence time of febrile neutropenia in DOC group.

Fig 3. Febrile neutropenia and neutrophil counts on day 8 versus age.

(A) in DOC group and (B) in FEC group, a scatter plot of age versus neutrophil count on day 8 is shown, patients experienced FN during a planned cycle were shown in punctuation mark (x) and who did not open circle (o).

Fig 4. Changes in neutrophil counts by oral dexamethasone pretreatment in TC treated patients.

Solid black line represents the absolute neutrophil counts without premedication oral dexamethasone and dashed line represent with oral dexamethasone premedication in TC treated patients.