Factors Associated with Absolute Neutrophil Count Dynamics and Docetaxel-Adryamicin-Cyclophosphamide (TAC) Chemotherapy Induced Neutropenia During Extended Filgrastim Administration in Breast Cancer Patients

Ami Ashariati, Ugroseno Yudho Bintoro, Merlyna Savitri, Muhammad Noor Diansyah, Putu Niken Ayu Amrita, Pradana Zaky Romadhon, Andi Yasmin Wijaya, Winona May Hendrata, Steven Sheng Looi, Ahmad Amin Mahmudin

Abstract


Background: Myelosuppressive effects of chemotherapy for breast cancer treatment may trigger chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN). Filgrastim has been widely used as prophylaxis against CIN and FN. However despite filgrastim administration, some study showed FN still occur and cause patient vulnerability to infection. This study aims to evaluate factors associated with Absolute Neutrophil Count (ANC) dynamics and Docetaxel-Adryamicin-Cyclophosphamide (TAC) CIN during extended filgrastim administration in breast cancer patients. Methods: Patients were selected among breast cancer in-patients who fulfilled the eligibility criteria. Patient characteristics data and ANC were collected. The entire patients received 5μg/kg/day filgrastim by subcutaneous injection 24 hours post-chemotherapy. ANC was monitored daily and filgrastim administration was stopped when ANC reached >10000/mm3 or 14 days of administration. Kruskall-Wallis test and Spearman Correlation test was performed to analyze ANC dynamics and CIN-related factors. Results: This study included 42 breast cancer patients. Patient age median was 52 (31-70) years old. ANC nadir could be observed around 5-7 days after chemotherapy and FN occurred in two out of 38 grade 4 neutropenia patients (4.8%). Critical ANC lasted for 1 day, 2 days, and 3 days respectively in 9 (23.7%), 25 (65.8%) and 4 (10.5%) patients. There was no correlation between neutropenia and age. ANC slope and recovery duration did not show a significant difference. However, depth of nadir is inversely correlated with the duration of ANC recovery (>10000/mm3) and the duration during the peak on the 2nd day until reaching nadir both with fair strength, r = −0.489 and r = −0.438 (p <0.05), respectively. No sepsis incidence had manifested. Conclusion: CIN still occured in breast cancer patient receiving filgrastim primary prophylaxis regardless of age and neutropenia severity. Nadir as the lowest point of ANC should be noted as a pivotal milestone for ANC slope and recovery evaluation.


Keywords


breast cancer; cancer; TAC chemotherapy; febrile neutropenia; filgrastim

References


Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.

Gerber B, Freund M, Reimer T. Recurrent breast cancer: treatment strategies for maintaining and prolonging good quality of life. Deutsches Ärzteblatt International. 2010;107(6):85–91.

Abdullah LN, Chow EK-H. Mechanisms of chemoresistance in cancer stem cells. Clin Transl Med. 2013;2(1):3.

Aapro M, Crawford J, Kamioner D. Prophylaxis of chemotherapy-induced febrile neutropenia with granulocyte colony-stimulating factors: Where are we now? Support Care Cancer. 2010;18(5):529–41.

Trotti A, Colevas A, Setser A, et al. Development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol. 2003;13(3):176–81.

Crawford J, Dale DC, Lyman GH. Chemotherapy-induced neutropenia: Risks, consequences, and new directions for its management. Cancer. 2004;100(2):228–37.

Ludwig H, Bokemeyer C, Aapro M, et al. Chemotherapy-induced neutropenia/febrile neutropenia prophylaxis with biosimilar filgrastim in solid tumors versus hematological malignancies: MONITOR-GCSF study. Futur Oncol. 2019;15(8):897–907.

Hima NA, Andrajati R, Radji M. Kejadian demam neutropenia pada pasien kanker payudara setelah menerima regimen kemoterapi TAC-G-CSF dan FAC di RSUP Dr. Hasan Sadikin Bandung . Indones J Clin Pharm. 2021;10(1):1.

Lee J, Lee JE, Kim Z, et al. Pegfilgrastim for primary prophylaxis of febrile neutropenia in breast cancer patients undergoing TAC chemotherapy. Ann Surg Treat Res. 2018;94(5):223–8.

Park KH, Lee S, Park JH, et al. A randomized, multi-center, open-label, phase III study of once-per-cycle DA-3031, a pegylated G-CSF, in comparison with daily filgrastim in patients receiving TAC chemotherapy for breast cancer. Support Care Cancer. 2013;25(2):505–11.

Coker RJ, Hunter BM, Rudge JW, et al. Emerging infectious diseases in southeast Asia: regional challenges to control. Lancet. 2011;377(9765):599–609.

Kubo K, Miyazaki Y, Murayama T, et al. A randomized, double-blind trial of pegfilgrastim versus filgrastim for the management of neutropenia during CHASE(R) chemotherapy for malignant lymphoma. Br J Haematol. 2016;174:563–70.

Klastersky J, de Naurois J, Rolston K, et al. Management of febrile neutropaenia: ESMO clinical practice guidelines. Ann Oncol. 2016;27:v111–v118.

Hulley SB, Cummings SR, Browner WS, Grady DG, Newman TB. Designing clinical research. Fourth edition. Philadelphia: Lippincot Williams & Wilkins, a Wolters Kluwer business; 2013. p. 79.

Smith TJ, Bohlke K, Lyman GH, et al. Recommendations for the use of WBC growth factors: American society of clinical oncology clinical practice guideline update. J Clin Oncol. 2015;33(28):3199–212.

Newburger PE, Dale DC. Evaluation and management of patients with isolated neutropenia. Semin Hematol. 2013;50(3):198–206.

Clemons M, Fergusson D, Simos D, et al. A multicentre, randomised trial comparing schedules of G-CSF (filgrastim) administration for primary prophylaxis of chemotherapy-induced febrile neutropenia in early stage breast cancer. Ann Oncol. 2020;31(7):951–7.

Jagarlamudi K, Ahluwalia M, Patel J, et al. A single dose filgastrim in the treatment of chemotherapy induced neutropenia. Blood. 2010;116(21):4774.

Heuser M, Ganser A, Bokemeyer C. Use of colony-stimulating factors for chemotherapy-associated neutropenia: Review of current guidelines. Semin Hematol. 2007;44(3):148–56.

Cortés de Miguel S, Calleja-Hernández MÁ, Menjón-Beltrán S, et al. Granulocyte colony-stimulating factors as prophylaxis against febrile neutropenia. Support Care Cancer. 2015;23(2):547–59.

Kim YM, Kim H, Lee S, et al. Airway G-CSF identifies neutrophilic inflammation and contributes to asthma progression. Eur Respir J. 2020;55(2):1900827.


Full Text: PDF

Refbacks

  • There are currently no refbacks.


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.