Abstract

Abstract Background and objective: Adjuvant chemotherapy is a critical part of systematic treatment of primary breast cancer. Chemotherapy induced neutropenia (CIN) is a common adverse event during adjuvant chemotherapy as well as a major factor limiting the implementation of the planned schedule of chemotherapy, causing the delay and drug reduction. Recombinant human granulocyte-colony stimulating factor (rhG-CSF) effectively stimulates the proliferation of neutrophil progenitors, promotes differentiation of these cells into mature neutrophils, and promote the release of neutrophils from the marrow, thus reducing the probability of CIN and related complications. Dose-Dense (DD) chemotherapy has become a commonly recommended regimen for primary breast cancer because of improvement of disease-free survival (DFS) and Overall Survival (OS). rhG-CSF should be administered prophylactically due to the high incidence of marrow suppression during dose-dense regimen. Little high-level clinical evidence to determine a unified rhG-CSF regimen. Single injection of long-acting pegfilgrastim and continuous multiple usage of short-acting filgrastim are two major ways to support dose-dense adjuvant chemotherapy. Based on a single database, we retrospectively assessed the efficacy and safety of two different rhG-CSF in supporting the dose-dense adjuvant chemotherapy (ddEC) in primary breast cancer, aiming to test the effectiveness of two different rhG-CSF as well as comparison of the advantages and disadvantages of the two methods. Methods: Data of patients who received dose-dense neoadjuvant chemotherapy with support of rhG-CSF at Peking University Cancer Hospital Breast Cancer Prevention and Treatment Center from Jul, 2015 to Jun, 2018 were retrospectively collected. All of these patients were planned to receive four cycles of ddEC (Epirubicin 100mg/m2 and cyclophosphamide 600 mg/m2) with using one of the following rhG-CSF schedules in parallel: 1) filgrastim 200-300μg/d on day 4, 6, 8, 10; 2) pegfilgrastim 6mg on day 2. The relative dose intensity (RDI) was calculated. Results: A total of 555 patients were enrolled and 2,176 cycles were completed in this study, 254 were treated with pegfilgrastim and 301 were treated with short-term filgrastim. 536 patients (96.6%, 95%CI: 95.1%-98.1%) completed all four cycles of treatment. Chemotherapy delay occurred in 42 patients (7.6%, 95%CI: 5.4%-9.8%) for 47 cycles (2.2%, 95%CI:11.6%-2.8%). 18 patients (3.2%, 95%CI:1.7% - 4.7%) had CIN-related chemotherapy delay. 532 patients achieved RDI≥85% (99.4%, 95%CI:98.7%-100%). FN occurred in 25 patients (4.5%, 95%CI:2.8% - 6.2%). In the subgroup of using pegfilgrastim, Chemotherapy delay occurred in 10 patients (3.9%, 95%CI:1.5%-6.3%), 243 patients achieved RDI≥85% (99.4%, 95%CI: 98.7%-100%), and FN occurred in 11 patients (4.3%, 95%CI: 1.8%-6.8%). In the subgroup of using short-term filgrastim, chemotherapy delay occurred in 15 patients (5.0%, 95%CI: 2.5%-7.5%), 289 patients achieved RDI≥85% (96%, 95CI: 93.8%-98.2%), and FN occurred in 14 patients (4.7%, 95%CI: 2.3%-7.1%). FN is more likely in patients using short-term filgrastim (6.3%vs2.8%, p=0.048), causing more chemotherapy delay (10.8%vs4.1%, p=0.003). Age, tumor size, status of axillary lymph nodes, pathological type and baseline of ANC were not correlated with non-febrile neutropenia in patients using short-term filgrastim. Conclusion: Two schedules of rhG-CSF are effective and safe in supporting four cycles of neoadjuvant ddEC. The effects of these two methods were similar in the completion rate of chemotherapy(RDI≥85%) and safety(incidence of FN). Citation Format: Jingyi Zhao, Yingjian He, Zhaoqing Fan, Jinfeng Li, Xinguang Wang, Yang Yang, Xue Chen, Tao Ouyang. Efficacy of two kinds of granulocyte colony-stimulating factors to support neoadjuvant dose-dense chemotherapy in primary breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-11-22.

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