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 1 st 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/mm 3 , average 494/mm 3 ) 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/mm 3 ). 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.

Kejadian Demam Neutropenia pada Pasien Kanker Payudara setelah Menerima Regimen Kemoterapi TAC-G-CSF dan FAC di RSUP Dr. Hasan Sadikin Bandung

“…Kejadian demam neutropenia pada regimen TAC dapat dicegah dengan pemberian profilaksis primer Granulocytecolony Stimulating Factor (G-CSF). [3][4][5] Namun, Badan Penyelenggara Jaminan Sosial (BPJS) Kesehatan tidak menanggung biaya penggunaan G-CSF sebagai profilaksis primer demam neutropenia, oleh karena itu, regimen FAC merupakan terapi pilihan saat ini meskipun TAC dengan profilaksis primer G-CSF dapat memperpanjang harapan hidup dan menurunkan risiko kekambuhan pasien. Selain regimen kemoterapi, beberapa kondisi seperti usia lanjut, stadium kanker, riwayat kemoterapi, dan kadar hemoglobin merupakan faktor risiko demam neutropenia yang diinduksi oleh kemoterapi.…”

“…Fluorourasil merupakan agen antimetabolik yang bekerja menghambat sintesis DNA neutrofil pada fase S dengan menghambat kerja enzim timidilat sintetase sehingga menghambat sintesis timidilat pirimidin yang merupakan nukleosida yang dibutuhkan untuk replikasi DNA. 5 Selain perbedaan mekanisme kerja, waktu terjadinya neutropenia setelah kemoterapi pada kedua agen kemoterapi juga berbeda. Pasien yang menerima Fluorourasil mengalami neutropenia pada hari ke 9-14, namun pasien yang menerima Dosetaksel mengalami neutropenia pada hari ke-7 atau lebih awal.…”

Incidência e manejo da neutropenia em pacientes submetidas ao protocolo AC-T no tratamento adjuvante de câncer de mama

“…A suspensão de tratamento durante a aplicação de docetaxel foi observada em 37 pacientes, sendo que somente 8 pacientes tiveram tratamento suspenso devido a episódios de neutropenia durante a aplicação de docetaxel, exclusivamente pacientes do grupo sem uso PP, mostrando o importante efeito protetor de suporte durante a administração de quimioterapia mielossupressora que essa classe de medicamentos apresenta (Ferreira et al, 2017;Furuya, 2019).…”

“…A neutropenia induzida por quimioterapia (NIQ) é uma reação incidente que ocorre principalmente pela supressão do sistema hematopoiético e comprometimento do sistema imunológico do paciente, descrita como uma queda na contagem absoluta de neutrófilos (CAN) circulantes no sangue periférico (Furuya, 2019). Existe clara correlação entre a presença de neutropenia severa e eventos de neutropenia febril (NF), uma emergência oncológica que está correlacionada a aumento de morbidade, mortalidade, estadia no hospital, utilização de antibióticos e fatores estimuladores de colônia de granulócitos (G-CSFs), consequentemente gerando um impacto significativo nos custos hospitalares (Aras, Bayraktar-Ekincioglu, & Killickap, 2020).…”

Evaluation of ABC gene polymorphisms on the pharmacokinetics and pharmacodynamics of capecitabine in colorectal patients: Implications for dosing recommendations

“…A continuous effort in the model‐informed drug discovery and development process has focused on the establishment of mathematical relationships between systemic drug exposure and response 12 . The semimechanistic model for chemotherapy‐induced myelosuppression published by Friberg et al, 13 currently the gold standard model, has allowed the continuous relationship between drug concentration and neutrophil count levels in monotherapy and combination regimens to be quantitatively characterized at the preclinical and clinical stages 14–20 . The development of grade 3‐4 (G 3/4 ) neutropenia (<1.0 × 10 9 cells/L) is a common and very common adverse event in CAP monotherapy and combination schemes with other cytostatic agents, like oxaliplatin, respectively 21 .…”