Incidence and management of neutropenia in patients undergoing the AC-T protocol in the adjuvant treatment of breast cancer
Keywords:Breast Neoplasms; Neutropenia; Chemotherapy-Induced Febrile Neutropenia; Drug-related side effects and adverse reactions.
Breast cancer is the most common tumor among women. The introduction of adjuvant systemic antineoplastic chemotherapy has the benefits of reducing the risk of recurrence and mortality from breast cancer. However, intrinsic to all chemotherapy, adverse reactions are observed, including chemotherapy-induced neutropenia, an incident reaction clearly related to febrile neutropenia events. Such events can have a significant impact on hospital costs and compromise the objective of adjuvant chemotherapy treatment. In a cross-sectional, descriptive, quantitative and retrospective study, 289 female patients with breast cancer and undergoing systemic chemotherapy adjuvant with the AC-T protocol, were evaluated in order to describe the incidence of neutropenia and identify the managements performed to maintain the treatment use. The gross incidence of neutropenia was 52.2% during the application of CA (doxorubicin and cyclophosphamide), 26.9% during the application of T (docetaxel) in patients who did not undergo primary prophylaxis (PP), and 15, 1% during application of T at the patients who made PP. Among the identified managements, use of antibiotic therapy (25.4%), use of granulocyte colony stimulating factors (23%) and postponement of the cycle (20.3%) were the most observed. The occurrence of neutropenia events during chemotherapy for breast cancer is imminent. However, it can lead to changes in the regimen that can compromise treatment. In this study, the occurrence of neutropenia points to the need to define protocols for the use of PP and management of the adverse reaction.
Aarts, M. J., Peters, F. P., Mandigers, C. M., Dercksen, M. W., Stouthard, J. M., Nortier, H. J., ... Tjan-Heijnen, V. C. (2013). Primary granulocyte colony-stimulating factor prophylaxis during the first two cycles only or throughout all chemotherapy cycles in patients with breast cancer at risk for febrile neutropenia. Journal of clinical oncology, 31(34), 4290–4296. doi.org/10.1200/JCO.2012.44.6229
Abotaleb, M., Kubatka, P., Caprnda, M., Varghese, E., Zolakova, B., Zubor, P., ... Büsselberg, D. (2018). Chemotherapeutic agents for the treatment of metastatic breast cancer: an update. Biomedicine & pharmacotherapy, 101, 458–477. doi.org/10.1016/j.biopha.2018.02.108
Aras, E., Bayraktar-Ekincioglu, A., & Kilickap, S. (2020). Risk assessment of febrile neutropenia and evaluation of g-csf use in patients with cancer: a real-life study. Supportive care in cancer, 28(2), 691–699. doi.org/10.1007/s00520-019-04879-x
Associação Brasileira para o Estudo da Obesidade e da Síndrome Metabólica. (2016). Diretrizes Brasileiras de Obesidade (4a ed.). Recuperado de https://abeso.org.br/wp-content/uploads/2019/12/Diretrizes-Download-Diretrizes-Brasileiras-de-Obesidade-2016.pdf
Bines, J., Earl, H., Buzaid, A. C., & Saad, E. D. (2014). Anthracyclines and taxanes in the neo/adjuvant treatment of breast cancer: does the sequence matter?. Annals of oncology, 25(6), 1079–1085. doi.org/10.1093/annonc/mdu007
Blum, J. L., Flynn, P. J., Yothers, G., Asmar, L., Geyer, C. E., Jacobs, S. A., … Wolmark, N. (2017). Anthracyclines in early breast cancer: the abc trials-usor 06-090, nsabp b-46-i/usor 07132, and nsabp b-49 (nrg oncology). Journal of clinical oncology, 35(23), 2647–2655. doi.org/10.1200/JCO.2016.71.4147
Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., & Jemal, A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians, 68(6), 394–424. doi.org/10.3322/caac.21492
Cardoso, F., Kyriakides, S., Ohno, S., Penault-Llorca, F., Poortmans, P., Rubio, I. T., ... ESMO Guidelines Committee. (2019). Early breast cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Annals of oncology, 30(8), 1194–1220. doi.org/10.1093/annonc/mdz173
Catala, G., Mebis, J., Jerusalem, G., Verhoeven, D., Awada, A., Bols, A., ... Machiels, J. P. (2020). Neutropenia management in patients receiving myelosuppressive polychemotherapy for early breast cancer in Belgium: brons study results. Acta clinica Belgica, 75(2), 128–135. doi.org/10.1080/17843286.2018.1563735
Faqeer, N. A., Mashni, O., Dawoud, R., Rumman, A., Hanoun, E., & Nazer, L. (2017). Comparing the incidence of febrile neutropenia resulting in hospital admission between the branded docetaxel and the generic formulations. Journal of clinical pharmacology, 57(2), 275–279. doi.org/10.1002/jcph.803
Ferreira, J. N., Correia, L. R. B. R., Oliveira, R. M. d., Watanabe, S. N., Possari, J. F., & Lima, A. F. C. (2017). Managing febrile neutropenia in adult cancer patients: an integrative review of the literature. Revista Brasileira de Enfermagem, 70(6), 1301-1308. doi.org/10.1590/0034-7167-2016-0247
Furuya Y. (2019). Early neutropenia on day 8 treated with adjuvant docetaxel-based chemotherapy in early breast cancer patients: putative mechanisms within the neutrophil pool system. PloS one, 14(4), e0215576. doi.org/10.1371/journal.pone.0215576
Hansson, E. K., & Friberg, L. E. (2012). The shape of the myelosuppression time profile is related to the probability of developing neutropenic fever in patients with docetaxel-induced grade IV neutropenia. Cancer chemotherapy and pharmacology, 69(4), 881–890. doi.org/10.1007/s00280-011-1769-7
Hegg, R., Mattar, A., Matos-Neto, J. N., Pedrini, J. L., Aleixo, S. B., Rocha, R. O., ... van-Eyll-Rocha, S. (2016). A phase III, randomized, non-inferiority study comparing the efficacy and safety of biosimilar filgrastim versus originator filgrastim for chemotherapy-induced neutropenia in breast cancer patients. Clinics, 71(10), 586–592. doi.org/10.6061/clinics/2016(10)06
Ho, M. Y., & Mackey, J. R. (2014). Presentation and management of docetaxel-related adverse effects in patients with breast cancer. Cancer management and research, 6, 253–259. doi.org/10.2147/CMAR.S40601
Instituto Nacional de Câncer José Alencar Gomes da Silva. (2019). Estimativa 2020: incidência de câncer no Brasil. Rio de Janeiro: INCA.
Kawatkar, A. A., Farias, A. J., Chao, C., Chen, W., Barron, R., Vogl, F. D., & Chandler, D. B. (2017). Hospitalizations, outcomes, and management costs of febrile neutropenia in patients from a managed care population. Supportive care in cancer, 25(9), 2787–2795. doi.org/10.1007/s00520-017-3692-x
Kim, C. G., Sohn, J., Chon, H., Kim, J. H., Heo, S. J., Cho, H., ... Kim, G. M. (2016). Incidence of febrile neutropenia in korean female breast cancer patients receiving preoperative or postoperative doxorubicin/cyclophosphamide followed by docetaxel chemotherapy. Journal of breast cancer, 19(1), 76–82. doi.org/10.4048/jbc.2016.19.1.76
Klastersky, J., de Naurois, J., Rolston, K., Rapoport, B., Maschmeyer, G., Aapro, M., ... ESMO Guidelines Committee (2016). Management of febrile neutropaenia: ESMO Clinical Practice Guidelines. Annals of oncology, 27(suppl 5), v111–v118. doi.org/10.1093/annonc/mdw325
Klastersky, J., Paesmans, M., Rubenstein, E. B., Boyer, M., Elting, L., Feld, R., ... Talcott, J. (2000). The Multinational Association for Supportive Care in Cancer risk index: A multinational scoring system for identifying low-risk febrile neutropenic cancer patients. Journal of clinical oncology, 18(16), 3038–3051. doi.org/10.1200/JCO.2000.18.16.3038
Ladwa, R., Kalas, T., Pathmanathan, S., Woodward, N., Wyld, D., & Sanmugarajah, J. (2018). Maintaining dose intensity of adjuvant chemotherapy in older patients with breast cancer. Clinical breast cancer, 18(5), e1181–e1187. doi.org/10.1016/j.clbc.2018.04.016
Minckwitz, G. von, Schwenkglenks, M., Skacel, T., Lyman, G. H., Pousa, A. L., Bacon, P., ... Aapro, M. S. (2009). Febrile neutropenia and related complications in breast cancer patients receiving pegfilgrastim primary prophylaxis versus current practice neutropaenia management: results from an integrated analysis. European journal of cancer, 45(4), 608–617. doi.org/10.1016/j.ejca.2008.11.021
Morrison, V. A., McCall, L., Muss, H. B., Jatoi, A., Cohen, H. J., Cirrincione, C. T., ... Hurria, A. (2018). The impact of actual body weight-based chemotherapy dosing and body size on adverse events and outcome in older patients with breast cancer: results from cancer and leukemia group b (calgb) trial 49907 (alliance a151436). Journal of geriatric oncology, 9(3), 228–234. doi.org/10.1016/j.jgo.2017.11.007
Nascimento, T. G. do, Andrade, M. de, Oliveira, R. A. de, Almeida, A. M. de, & Gozzo, T. de O. (2014). Neutropenia: occurrence and management in women with breast cancer receiving chemotherapy. Revista Latino-Americana de Enfermagem, 22(2), 301-308. doi.org/10.1590/0104-1169.3305.2416
National Comprehensive Cancer Network. (2020). Myeloid Growth Factors (Version 2.2020). Recuperado de http://www.nccn.org/professionals/physician_gls/pdf/growthfactors.pdf.
Pereira, A. S., Shitsuka, D. M., Pereira, F. J., & Shitsuka, R. (2018). Metodologia da pesquisa científica. Santa Maria, RS: UAB/NTE/UFSM. Recuperado de https://www.ufsm.br/app/uploads/sites/358/2019/02/Metodologia-da-Pesquisa-Cientifica_final.pdf
Pereira, L. C., Nogueira, T. A., Barbosa, L. A., Calil-Elias, S., Castilho, S. R. de. (2015). Adverse reactions to docetaxel: an active survey. Brazilian Journal of Pharmaceutical Sciences, 51, 551-559.doi.org/10.1590/S1984-82502015000300007.
Sociedade Brasileirade Farmacêuticos em Oncologia. (2011). Guia para notificação de reações adversas em oncologia (2a ed.). São Paulo: Conectfarma Publicações Científicas.
Wang, L., Baser, O., Kutikova, L., Page, J. H., & Barron, R. (2015). The impact of primary prophylaxis with granulocyte colony-stimulating factors on febrile neutropenia during chemotherapy: a systematic review and meta-analysis of randomized controlled trials. Supportive care in cancer, 23(11), 3131–3140. doi.org/10.1007/s00520-015-2686-9
World Health Organization. (2020). The ATC classification structure and principles. Recuperado de http://www.whocc.no/atc_ddd_index/.
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