Real-World Incidence of Febrile Neutropenia among Patients Treated with Single-Agent Amrubicin: Necessity of the Primary Prophylactic Administration of Granulocyte Colony-Stimulating Factor

Abstract

Background: Single-agent amrubicin chemotherapy is a key regimen, especially for small cell lung cancer (SCLC); however, it can cause severe myelosuppression. Purpose: The purpose of this study was to determine the real-world incidence of febrile neutropenia (FN) among patients treated with single-agent amrubicin chemotherapy for thoracic malignancies. Patients and methods: The medical records of consecutive patients with thoracic malignancies, including SCLC and non-small cell lung cancer (NSCLC), who were treated with single-agent amrubicin chemotherapy in cycle 1 between January 2010 and March 2020, were retrospectively analyzed. Results: One hundred and fifty-six patients from four institutions were enrolled. Their characteristics were as follows: median age (range): 68 (32–86); male/female: 126/30; performance status (0/1/2): 9/108/39; SCLC/NSCLC/others: 111/30/15; and prior treatment (0/1/2/3-): 1/96/31/28. One hundred and thirty-four (86%) and 97 (62%) patients experienced grade 3/4 and grade 4 neutropenia, respectively. One hundred and twelve patients (72%) required therapeutic G-CSF treatment, and 47 (30%) developed FN. Prophylactic PEG-G-CSF was not used in cycle 1 in any case. The median overall survival of the patients with FN was significantly shorter than that of the patients without FN (7.2 vs. 10.0 months, p = 0.025). Conclusions: The real-world incidence rate of FN among patients with thoracic malignancies that were treated with single-agent amrubicin chemotherapy was 30%. It is suggested that prophylactic G-CSF should be administered during the practical use of single-agent amrubicin chemotherapy for patients who have already received chemotherapy.

Influencing factors of efficacy and long‐term use of amrubicin in patients with small cell lung cancer

“…Prophylactic granulocyte colony‐stimulating factor (G‐CSF) administration is recommended in AMR therapy for recurrent small cell lung cancer because of the high incidence of febrile neutropenia. 16 There was no significant difference in the incidence of febrile neutropenia between the study groups. However, febrile neutropenia could lead to deterioration of the patient's general condition and discontinuation of chemotherapy.…”

“…In total, 21.2% of the patients developed febrile neutropenia. Prophylactic granulocyte colony‐stimulating factor (G‐CSF) administration is recommended in AMR therapy for recurrent small cell lung cancer because of the high incidence of febrile neutropenia 16 . There was no significant difference in the incidence of febrile neutropenia between the study groups.…”

“…However, the incidence of febrile neutropenia may also increase when AMR is administered without a dose reduction after the second cycle. Importantly, there have been reports that the development of febrile neutropenia during AMR treatment is associated with a shorter prognosis 10,16 . Maintaining high AMR doses may increase antitumor efficacy 16 .…”

Phase I study of amrubicin plus cisplatin and concurrent accelerated hyperfractionated thoracic radiotherapy for limited‐disease small cell lung cancer: protocol of ACIST study

“…In a phase III study, which compared the efficacy of AP and that of IP in treatment naive Japanese patients with ED‐SCLC, the dose of AMR was reduced from 40 mg/m 2 to 35 mg/m 2 because of the high incidence of severe hematological toxicities 15 . Furthermore, our retrospective study revealed that the real‐world incidence rate of febrile neutropenia among patients with thoracic malignancies that were treated with single‐agent AMR chemotherapy was 30% 16 . Based on these findings for Japanese patients, the dose of 35 mg/m 2 AMR from second cycle to fourth is predicted as the suitable dose in this protocol.…”

“… 15 Furthermore, our retrospective study revealed that the real‐world incidence rate of febrile neutropenia among patients with thoracic malignancies that were treated with single‐agent AMR chemotherapy was 30%. 16 Based on these findings for Japanese patients, the dose of 35 mg/m 2 AMR from second cycle to fourth is predicted as the suitable dose in this protocol.…”