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Abstract
Background: Granulocyte colony-stimulating factor (GCSF) is a primary regulator of the granulopoiesis process, which mobilizes stem cells from the bone marrow to the blood vessels. Filgrastim and lenograstim are the types of GCSF that have been widely used.
Objective: This research aims to study the comparative therapeutic outcomes and cost-effectiveness of filgrastim and lenograstim therapies in colorectal cancer patients undergoing chemotherapy with the FOLFOX regimen.
Method: This research was conducted at the pharmacy installation of the Dr. Kariadi Central General Hospital (RSUP Dr. Kariadi) from December 2023 to January 2024. It is observational research with a retrospective pre-posttest cohort study design that evaluates the comparative effectiveness and costs of filgrastim and lenograstim therapies in patients with neutropenia based on an increase in white blood cells (WBC) and absolute neutrophil count (ANC) scores of patients. The data was analyzed using the unpaired comparative analysis method and using the cost-effectiveness analysis (CEA) method to determine the cost-effectiveness. The observations were carried out twice, before and after administering the GCSF therapy. The samples consisted of 25 patients divided into two treatment groups.
Results: The average scores of WBC and ANC levels in 15 patients who received filgrastim therapy were 2000 cells/mm3 and 666 cells/mm3. At the same time, the WBC and ANC levels in 10 patients who received lenograstim therapy were 1980 cells/mm3 and 449 cells/mm3. After administering the GCSF therapy, there was a significant increase in WBC and ANC levels (p<0.05) in each group. Still, there was no significant difference in the increase in WBC and ANC between the groups receiving filgrastim and lenograstim (p>0.05). The CEA analysis results showed that an increase of 1 cell/ml of WBC score cost Rp24.2 for filgrastim and Rp347 for lenograstim. In contrast, an increase of 1 cell/ml of ANC score cost Rp111.8 for filgrastim and Rp1572.5 for lenograstim.
Conclusion: This research concludes that filgrastim is as effective as lenograstim, yet filgrastim is considered more cost-effective than lenograstim.
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References
- American Academy of Allergy, A. I. (2023). Neutropenia Defined. Milwaukee: US and Canada. https://www.aaaai.org (accessed on 27th August 2023).
- Bracci, L., Schiavoni, G., Sistigu, A., & Belardelli, F. (2014). Immune-Based Mechanisms of Cytotoxic Chemotherapy: Implications For The Design of Novel and Rationale-Based Combined Treatments Against Cancer. Cell Death and Differentiation, 21(1), 15–25. https://doi.org/10.1038/cdd.2013.67
- Budiana, I. N. G., & Febiani, M. (2017). Approach to the Patient with Abnormal Cerebrospinal Fluid Glucose Content. Cerebrospinal Fluid in Clinical Practice, 11(2), 77–82. https://doi.org/10.1016/B978-141602908-3.50034-0
- Citraningtyas, G., Ruru, R. I., & Nalang, A. (2018). Analisis Efektifitas Biaya Penggunaan Antibiotik Sefiksim dan Sefotaksim Pasien Diare di Rumah Sakit X Tahun 2017. Jurnal Manajemen Dan Pelayanan Farmasi, 8(4), 145–152.
- Cooper, K. L., Madan, J., Whyte, S., Stevenson, M. D., & Akehurst, R. L. (2011). Granulocyte Colony-Stimulating Factors For Febrile Neutropenia Prophylaxis Following Chemotherapy: Systematic Review and Meta-Analysis. BMC Cancer, 11(404), 1–11. https://doi.org/10.1186/1471-2407-11-404
- Dahlan, S. M. (2009). Statistik untuk kodekteran dan kesehatan Deskriptif, Bivariat, dan Multivariat Dilengkapi Aplikasi dengan Menggunakan SPSS. Salemba Medika.
- Garófolo, A. (2013). Neutropenic Diet and Quality of Food: A Critical Analysis. Revista Brasileira de Hematologia e Hemoterapia, 35(2), 79–80. https://doi.org/10.5581/1516-8484.20130022
- Klastersky, J., de Naurois, J., Rolston, K., Rapoport, B., Maschmeyer, G., Aapro, M., Herrstedt, J., & on behalf of the ESMO Guidelines Committee. (2016). Management of Febrile Neutropaenia: ESMO Clinical Practice Guidelines. Annals of Oncology, 27(5), 111–118. https://doi.org/10.1093/annonc/mdw325
- Lorensia, A., & Doddy, D. Q. (2016). Farmakoekonomi, Edisi Kedua. Ubaya Press.
- Mitchell, S., Li, X., Woods, M., Garcia, J., Hebard-Massey, K., Barron, R., & Samuel, M. (2016). Comparative Effectiveness of Granulocyte Colony-Stimulating Factors To Prevent Febrile Neutropenia and Related Complications In Cancer Patients In Clinical Practice: A Systematic Review. Journal of Oncology Pharmacy Practice, 22(5), 702–716.
- Nalang, A., Citraningtyas, G., & Lolo, W. A. (2018). Analisis Efektivitas Biaya (Cost Effectiveness Analysis) Pengobatan Pneumonia Menggunakan Antibiotik Seftriakson dan Sefotaksim di RSUP Prof. Dr. R. D. Kandou Manado. Jurnal Ilmiah Farmasi, 7(3), 321–329.
- Orciuolo, E., Buda, G., Marturano, E., Mauro, E., Milone, G., Cangialosi, C., Di Renzo, N., Pastore, D., Specchia, G., De Paolis, M. R., Mazza P., Pietrantuono, G., & Petrini, M. (2011). Lenograstim reduces the incidence of febrile episodes, when compared with filgrastim, in multiple myeloma patients undergoing stem cell mobilization. Leukimia Research, 35 (7), 899-903. https://doi.org/10.1016/j.leukres.2010.10.029.
- Pilatova, K., Bencsikova, B., Demlova, R., Valik, D., & Zdrazilova-Dubska, L. (2018). Myeloid-Derived Suppressor Cells (MDSCs) In Patients With Solid Tumors: Considerations For Granulocyte Colony-Stimulating Factor Treatment. Cancer Immunology, Immunotherapy, 67(12), 1919–1929. https://doi.org/10.1007/s00262-018-2166-4
- Ria, R., Gasparre, T., Mangialardi, G., Bruno, A., Iodice, G., Vacca, A., & Dammacco, F. (2010). Comparison Between Filgrastim and Lenograstim Plus Chemotherapy For Mobilization of PBPCs. Bone Marrow Transplantation, 45(2), 277–281. https://doi.org/10.1038/bmt.2009.150
- Scotte, F., Simon, H., Laplaige, P., Antoine, E. C., Spasojevic, C., Texier, N., Gouhier, K., & Chouaid, C. (2024). Febrile Neutropenia Prophylaxis, G-CSF Physician Preferences: Discrete-Choice Experiment. BMJ Supportive and Palliative Care, 14, 1936–1943. https://doi.org/10.1136/bmjspcare-2021-003082
- Smith, T. J., Bohlke, K., Lyman, G. H., Carson, K. R., Crawford, J., Cross, S. J., Goldberg, J. M., Khatcheressian, J. L., Leighl, N. B., Perkins, C. L., Somlo, G., Wade, J. L., Wozniak, A. J., & Armitage, J. O. (2015). Recommendations for the Use ofWBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update. Journal of Clinical Oncology, 33(28), 3199–3212. https://doi.org/10.1200/JCO.2015.62.3488
- Tseng, T.-H., Chiang, S.-C., Hsu, J. C., & Ko, Y. (2024). Cost-effectiveness Analysis of Granulocyte Colony-Stimulating Factors For The Prophylaxis of Chemotherapy-Induced Febrile Neutropenia In Patients With Breast Cancer In Taiwan. PLoS ONE, 19(6), 1–16. https://doi.org/10.1371/journal.pone.0303294
- Uddin, S., Russell, P., Farrell, M., Davy, B., Taylor, J., & Agrawal, S. G. (2015). Use of Biosimilar Filgrastim Compared With Lenograstim In Autologous Haematopoietic Stem-Cell Transplant and In Sibling Allogeneic Transplant. Therapeutic Advances in Hematology, 6(2), 53–60. https://doi.org/10.1177/2040620714565962
- Utomo, A., Widyati, W., & Susilo, D. H. (2020). Efektivitas Profilaksis Primer Filgrastim Pada Pasien Kanker Payudara terhadap Insiden Neutropenia. MPI (Media Pharmaceutica Indonesiana), 3(1), 52–59. https://doi.org/10.24123/mpi.v3i1.2831
- Wang, Y., Zhao, C., Ma, P., & Jiang, D. (2023). Outcome and Cost-Effectiveness Analysis of Long-acting G-CSF as Primary Prophylaxis of Neutropenia Induced by Chemotherapy in Breast Cancer Patients, From a Retrospective Study. Cancer Control, 30, 1–10. https://doi.org/10.1177/10732748221140289
References
American Academy of Allergy, A. I. (2023). Neutropenia Defined. Milwaukee: US and Canada. https://www.aaaai.org (accessed on 27th August 2023).
Bracci, L., Schiavoni, G., Sistigu, A., & Belardelli, F. (2014). Immune-Based Mechanisms of Cytotoxic Chemotherapy: Implications For The Design of Novel and Rationale-Based Combined Treatments Against Cancer. Cell Death and Differentiation, 21(1), 15–25. https://doi.org/10.1038/cdd.2013.67
Budiana, I. N. G., & Febiani, M. (2017). Approach to the Patient with Abnormal Cerebrospinal Fluid Glucose Content. Cerebrospinal Fluid in Clinical Practice, 11(2), 77–82. https://doi.org/10.1016/B978-141602908-3.50034-0
Citraningtyas, G., Ruru, R. I., & Nalang, A. (2018). Analisis Efektifitas Biaya Penggunaan Antibiotik Sefiksim dan Sefotaksim Pasien Diare di Rumah Sakit X Tahun 2017. Jurnal Manajemen Dan Pelayanan Farmasi, 8(4), 145–152.
Cooper, K. L., Madan, J., Whyte, S., Stevenson, M. D., & Akehurst, R. L. (2011). Granulocyte Colony-Stimulating Factors For Febrile Neutropenia Prophylaxis Following Chemotherapy: Systematic Review and Meta-Analysis. BMC Cancer, 11(404), 1–11. https://doi.org/10.1186/1471-2407-11-404
Dahlan, S. M. (2009). Statistik untuk kodekteran dan kesehatan Deskriptif, Bivariat, dan Multivariat Dilengkapi Aplikasi dengan Menggunakan SPSS. Salemba Medika.
Garófolo, A. (2013). Neutropenic Diet and Quality of Food: A Critical Analysis. Revista Brasileira de Hematologia e Hemoterapia, 35(2), 79–80. https://doi.org/10.5581/1516-8484.20130022
Klastersky, J., de Naurois, J., Rolston, K., Rapoport, B., Maschmeyer, G., Aapro, M., Herrstedt, J., & on behalf of the ESMO Guidelines Committee. (2016). Management of Febrile Neutropaenia: ESMO Clinical Practice Guidelines. Annals of Oncology, 27(5), 111–118. https://doi.org/10.1093/annonc/mdw325
Lorensia, A., & Doddy, D. Q. (2016). Farmakoekonomi, Edisi Kedua. Ubaya Press.
Mitchell, S., Li, X., Woods, M., Garcia, J., Hebard-Massey, K., Barron, R., & Samuel, M. (2016). Comparative Effectiveness of Granulocyte Colony-Stimulating Factors To Prevent Febrile Neutropenia and Related Complications In Cancer Patients In Clinical Practice: A Systematic Review. Journal of Oncology Pharmacy Practice, 22(5), 702–716.
Nalang, A., Citraningtyas, G., & Lolo, W. A. (2018). Analisis Efektivitas Biaya (Cost Effectiveness Analysis) Pengobatan Pneumonia Menggunakan Antibiotik Seftriakson dan Sefotaksim di RSUP Prof. Dr. R. D. Kandou Manado. Jurnal Ilmiah Farmasi, 7(3), 321–329.
Orciuolo, E., Buda, G., Marturano, E., Mauro, E., Milone, G., Cangialosi, C., Di Renzo, N., Pastore, D., Specchia, G., De Paolis, M. R., Mazza P., Pietrantuono, G., & Petrini, M. (2011). Lenograstim reduces the incidence of febrile episodes, when compared with filgrastim, in multiple myeloma patients undergoing stem cell mobilization. Leukimia Research, 35 (7), 899-903. https://doi.org/10.1016/j.leukres.2010.10.029.
Pilatova, K., Bencsikova, B., Demlova, R., Valik, D., & Zdrazilova-Dubska, L. (2018). Myeloid-Derived Suppressor Cells (MDSCs) In Patients With Solid Tumors: Considerations For Granulocyte Colony-Stimulating Factor Treatment. Cancer Immunology, Immunotherapy, 67(12), 1919–1929. https://doi.org/10.1007/s00262-018-2166-4
Ria, R., Gasparre, T., Mangialardi, G., Bruno, A., Iodice, G., Vacca, A., & Dammacco, F. (2010). Comparison Between Filgrastim and Lenograstim Plus Chemotherapy For Mobilization of PBPCs. Bone Marrow Transplantation, 45(2), 277–281. https://doi.org/10.1038/bmt.2009.150
Scotte, F., Simon, H., Laplaige, P., Antoine, E. C., Spasojevic, C., Texier, N., Gouhier, K., & Chouaid, C. (2024). Febrile Neutropenia Prophylaxis, G-CSF Physician Preferences: Discrete-Choice Experiment. BMJ Supportive and Palliative Care, 14, 1936–1943. https://doi.org/10.1136/bmjspcare-2021-003082
Smith, T. J., Bohlke, K., Lyman, G. H., Carson, K. R., Crawford, J., Cross, S. J., Goldberg, J. M., Khatcheressian, J. L., Leighl, N. B., Perkins, C. L., Somlo, G., Wade, J. L., Wozniak, A. J., & Armitage, J. O. (2015). Recommendations for the Use ofWBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update. Journal of Clinical Oncology, 33(28), 3199–3212. https://doi.org/10.1200/JCO.2015.62.3488
Tseng, T.-H., Chiang, S.-C., Hsu, J. C., & Ko, Y. (2024). Cost-effectiveness Analysis of Granulocyte Colony-Stimulating Factors For The Prophylaxis of Chemotherapy-Induced Febrile Neutropenia In Patients With Breast Cancer In Taiwan. PLoS ONE, 19(6), 1–16. https://doi.org/10.1371/journal.pone.0303294
Uddin, S., Russell, P., Farrell, M., Davy, B., Taylor, J., & Agrawal, S. G. (2015). Use of Biosimilar Filgrastim Compared With Lenograstim In Autologous Haematopoietic Stem-Cell Transplant and In Sibling Allogeneic Transplant. Therapeutic Advances in Hematology, 6(2), 53–60. https://doi.org/10.1177/2040620714565962
Utomo, A., Widyati, W., & Susilo, D. H. (2020). Efektivitas Profilaksis Primer Filgrastim Pada Pasien Kanker Payudara terhadap Insiden Neutropenia. MPI (Media Pharmaceutica Indonesiana), 3(1), 52–59. https://doi.org/10.24123/mpi.v3i1.2831
Wang, Y., Zhao, C., Ma, P., & Jiang, D. (2023). Outcome and Cost-Effectiveness Analysis of Long-acting G-CSF as Primary Prophylaxis of Neutropenia Induced by Chemotherapy in Breast Cancer Patients, From a Retrospective Study. Cancer Control, 30, 1–10. https://doi.org/10.1177/10732748221140289