Pegfilgrastim for primary prophylaxis of febrile neutropenia in breast cancer patients undergoing TAC chemotherapy

Lee, Jihyoun; Lee, Jong Eun; Kim, Zisun; Han, Sun Wook; Hur, Sung Mo; Kim, Sung Yong; Lee, Min Hyuk; Lim, Cheol Wan

doi:10.4174/astr.2018.94.5.223

Cited by 15 publications

(20 citation statements)

References 26 publications

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“…Moreover, plinabulin did not affect endogenous G-CSF levels in bone marrow or plasma in the models tested. Data therefore indicate that plinabulin may serve as an alternative therapy to G-CSF for prophylactic CIN therapy and should also be considered for testing in combination with G-CSF therapies, especially in settings where adequate ANC control by G-CSF therapy is lacking [e.g., 8].…”

Section: Discussionmentioning

confidence: 99%

“…G-CSF adverse effects include bone pain, splenic rupture, acute respiratory distress syndrome, allergic reactions including anaphylaxis and allergies to acrylics, sickle cell disorder, glomerulonephritis, capillary leak syndrome, leukocytosis and the potential for tumor growth stimulatory effects on malignant cells [5,7]. Finally, with more aggressive chemotherapy regimens such as Taxotere ® + Adriamycin ® + cyclophosphamide (TAC), grade 3 or 4 neutropenia still occurs in > 90% of patients, despite G-CSF prophylactic therapy [8]. To address these issues, novel non-GSF-based treatments for CIN are being sought as alternatives or supplements to G-CSF therapies [7].…”

Section: Introductionmentioning

confidence: 99%

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Plinabulin ameliorates neutropenia induced by multiple chemotherapies through a mechanism distinct from G-CSF therapies

Tonra¹,

Lloyd²,

Mohanlal³

et al. 2019

Cancer Chemother Pharmacol

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Purpose Chemotherapy-induced neutropenia (CIN) increases the risk of infections and mortality in cancer patients. G-CSF therapies are approved for the treatment of CIN, but non-G-CSF therapies are needed to increase efficacy and minimize side effects. Plinabulin is an inhibitor of tubulin polymerization that ameliorates CIN caused in patients by the microtubule stabilizer docetaxel. The present study evaluates the potential of plinabulin to reduce neutropenia induced by chemotherapies of different classes in a manner not dependent on increasing G-CSF. Methods The anti-CIN benefits of plinabulin were tested in rodents co-treated with docetaxel, cyclophosphamide or doxorubicin. Effects on G-CSF levels were evaluated in tissues by immunoassay. Flow cytometry was utilized to test treatment effects on femur bone marrow cell counts from immunocompetent mice-bearing orthotopic 4T1 breast cancer tumors. Results Plinabulin alleviated neutropenia induced by microtubule stabilizing, DNA cross-linking and DNA intercalating chemotherapies, yet did not affect bone marrow or blood G-CSF levels. The number of lineage − /Sca1 + /c-Kit + (LSK) hematopoietic stem/progenitor cells (HSPC) in murine bone marrow collected 2 days after treatment was not affected by docetaxel monotherapy despite increased plasma G-CSF in this group. LSK cell number was, however, increased when plinabulin was combined with docetaxel, without affecting G-CSF. Conclusions Results support the clinical testing of plinabulin as a non-G-CSF-based treatment for CIN associated with chemotherapies of different mechanisms. Results also support HSPC as a focal point for future mechanism-of-action work aimed at understanding the ability of plinabulin to reduce this serious side effect of cytotoxic therapy in cancer patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Plinabulin ameliorates neutropenia induced by multiple chemotherapies through a mechanism distinct from G-CSF therapies

Tonra¹,

Lloyd²,

Mohanlal³

et al. 2019

Cancer Chemother Pharmacol

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“…The use of long-acting G-CSF is the most important way to overcome the limitations caused by the hematologic toxicity of the TAC regimen. Treatment with long-acting G-CSF reduces FN and results in better supportive care and an improved quality of life in breast cancer patients [ 13 16 17 21 ]. In our study, the incidence of FN decreased from 54.2% to 21.2% in patients, and from 36.1% to 9.1% in all chemotherapy cycles, after the use of primary prophylactic pegfilgrastim.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies conducted in Korea reported that the overall frequency of FN during adjuvant TAC chemotherapy was significantly higher than that observed in previous studies conducted in Western countries (42.5%–63.4% vs. 17%–26%) [ 18 19 20 ]. However, only 1 study with a small sample size reported the clinical effect of primary prophylactic therapy using pegfilgrastim on the incidence of FN during adjuvant TAC chemotherapy in Korea [ 21 ]. Therefore, the aim of the current study was to evaluate not only the difference in the incidence of FN but also the difference in the risk of FN-related complications and hospitalization according to whether Korean patients with advanced breast cancer received primary prophylactic support with pegfilgrastim during adjuvant TAC chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Clinical Impact of Primary Prophylactic Pegfilgrastim in Breast Cancer Patients Receiving Adjuvant Docetaxel-Doxorubicin-Cyclophosphamide Chemotherapy

et al. 2020

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Purpose The regimen including concurrent docetaxel, doxorubicin, and cyclophosphamide (TAC) has been categorized as an important risk factor for febrile neutropenia (FN). This comparative study examined the clinical impact of long-acting granulocyte colony-stimulating factor (G-CSF) (pegfilgrastim) during adjuvant TAC chemotherapy in Korean patients with advanced breast cancer. Methods We analyzed data from 239 patients who received 6 cycles of adjuvant TAC chemotherapy. We categorized patients into 2 groups according to the use of primary prophylactic pegfilgrastim and compared the incidence and risk of FN, hospital care costs, and survival in the 2 groups. Results The incidence of FN decreased from 54.2% to 21.2% in all patients, after the use of pegfilgrastim. The analysis of a total of 1,432 chemotherapy cycles showed that the incidence of FN decreased from 36.1% to 9.1% after the use of pegfilgrastim. Moreover, the decrease in the incidence of FN with the use of pegfilgrastim resulted in a significant decrease in the mean duration of neutropenia (4.15 to 1.29 days), the risk of hospitalization (99.5% to 29.7%) and the mean total hospital care cost (USD 3,038 to USD 2,347). High relative dose intensity (RDI) in patients treated with pegfilgrastim than in those not treated with pegfilgrastim (99.18% vs. 93.85%) was associated with a better overall survival ( p = 0.033). Conclusions The use of pegfilgrastim during adjuvant TAC chemotherapy was significantly associated with a decrease in the incidence and risk of FN, hospital care costs, and risk of death compared to the use of adjuvant TAC without primary prophylaxis.

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“…Adapun faktor risiko yang berpengaruh secara langsung terhadap insiden neutropenia diantaranya adalah usia (p = 0,000), LPT (p = 0,037), jenis kemoterapi (p = 0,000), siklus kemoterapi (p = 0,000), dan regimen kemoterapi (p = 0,000 [7,15]. Penggunaan profilaksis G-CSF pada pasien dengan usia >65 tahun yang menderita solid tumor dapat menurunkan perawatan di rumah sakit akibat FN dari 9% menjadi 5% [16].…”

Section: Analisis Faktor Risikounclassified

Efektivitas Profilaksis Primer Filgrastim Pada Pasien Kanker Payudara terhadap Insiden Neutropenia

Utomo

Widyati

Susilo

2020

MPI

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Kejadian febrile neutropenia menyebabkan penundaan jadwal kemoterapi, penurunan dosis kemoterapi, bahkan dapat menghentikan proses kemoterapi yang harus dijalani. Hal ini dapat berakibat pada penurunan tingkat keberhasilan terapi pada pasien kanker payudara. Kejadian neutropenia dapat dicegah dengan pemberian profilaksis primer granulocyte colony-stimulating factor (G-CSF), seperti filgrastim. Pemberian filgrastim dapat mengurangi risiko terjadinya febrile neutropenia, perawatan di Rumah Sakit, dan kematian pada pasien kanker payudara. Oleh karena itu, penelitian ini dilakukan untuk menganalisis efektivitas pemberian profilaksis filgrastim primer pada pasien kanker payudara yang mendapat kemoterapi. Penelitian ini merupakan jenis penelitian observasional analitik dengan rancang bangun prospective cohort study. Sampel yang digunakan yaitu 87 pasien kanker payudara yang sedang menjalani kemoterapi. Variabel yang diteliti adalah insiden neutropenia dan faktor risiko yang menyebabkan neutropenia. Hasil penelitian menunjukkan bahwa faktor risiko yang berpengaruh secara langsung terhadap insiden neutropenia adalah usia (p = 0,000), luas permukaan tubuh (p = 0,037), jenis kemoterapi (p = 0,000), siklus kemoterapi (p = 0,000), dan regimen kemoterapi (p = 0,000). Adanya profilaksis filgrastim primer efektif dalam menurunkan insiden neutropenia.

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Pegfilgrastim for primary prophylaxis of febrile neutropenia in breast cancer patients undergoing TAC chemotherapy

Cited by 15 publications

References 26 publications

Plinabulin ameliorates neutropenia induced by multiple chemotherapies through a mechanism distinct from G-CSF therapies

Plinabulin ameliorates neutropenia induced by multiple chemotherapies through a mechanism distinct from G-CSF therapies

Clinical Impact of Primary Prophylactic Pegfilgrastim in Breast Cancer Patients Receiving Adjuvant Docetaxel-Doxorubicin-Cyclophosphamide Chemotherapy

Efektivitas Profilaksis Primer Filgrastim Pada Pasien Kanker Payudara terhadap Insiden Neutropenia

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