Clinical Outcomes of Secondary Prophylactic Granulocyte Colony-Stimulating Factors in Breast Cancer Patients at a Risk of Neutropenia with Doxorubicin and Cyclophosphamide-Based Chemotherapy

Jae Hee Choi,Ji Eun Kang,Min Jung Geum,Nam Gi Park,Yun Kyoung Oh,Sandy Jeong Rhie

doi:10.3390/ph14111200

Abstract

Doxorubicin and cyclophosphamide (AC)-based chemotherapy has been a standard regimen for early-stage breast cancer (ESBC) with an intermediate risk (10–20%) of febrile neutropenia (FN). Secondary prophylaxis of granulocyte colony-stimulating factor (G-CSF) is considered in patients receiving AC-based chemotherapy; however, relevant studies are limited. Here, we retrospectively reviewed the electronic medical records of 320 patients who completed adjuvant AC-based chemotherapy from September 2016 to September 2020. Approximately 46.6% of the patients developed severe neutropenic events (SNE) during AC-based chemotherapy. Secondary prophylaxis of G-CSF reduced the risk of recurrent SNE (p < 0.01) and the relative dose intensity (RDI) < 85% (p = 0.03) in patients who had experienced SNE during AC-based chemotherapy. Age ≥ 65 years (p = 0.02) and alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 60 IU/L (p = 0.04) were significant risk factors for RDI < 85%. The incidences of FN, grade 4 neutropenia, unscheduled hospitalization, and interruption to the dosing regimen were reduced in patients administered secondary prophylaxis with G-CSF (before vs. after administration: FN, 19.4% vs. 4.6%; grade 4 neutropenia, 86.1% vs. 14.8%; unscheduled hospitalization, 75.9% vs. 11.1%; interruption to the dosing regimen, 18.5% vs. 8.3%). This study indicated the importance of active intervention of G-CSF use to prevent recurrent SNE and improve clinical outcomes in patients with breast cancer who receive AC-based chemotherapy.

Highlights

We investigated the effects of secondary prophylactic administration of granulocyte colony-stimulating factor (G-CSF) and the risk factors of the recurrent Febrile neutropenia (FN), grade 4 neutropenia, and relative dose intensity (RDI) < 85% in Korean patients with breast cancer who received AC-based chemotherapy
Twenty-one patients were excluded from the study because six were administered primary prophylactic G-CSF, nine had previous chemotherapy, four had hepatic or renal dysfunction, and two had missing values in laboratory tests
Secondary prophylaxis of G-CSF was defined as the administration of G-CSF to a patient who had experienced FN or grade 4 neutropenia to reduce their risk of neutropenia from subsequent chemotherapy

Summary

Introduction

Adjuvant chemotherapy for patients with early-stage breast cancer (ESBC) reduces the risk of recurrence and mortality [1,2]. Doxorubicin-and-cyclophosphamide (AC)-based chemotherapy is the most accepted standard regimen for ESBC [3,4]. Febrile neutropenia (FN) and grade 4 neutropenia are serious hematologic adverse reactions to chemotherapy that contains myelotoxic agents. They increase the risk of rapid infection progress and may lead to death. The incidences of FN and grade 4 neutropenia in patients with AC-based chemotherapy range from 4.6–29.5% and 44.6–66.4%, respectively [5,6,7,8].

Methods

Results

Discussion

Conclusion