Combination of interferons in patients with high-grade brain tumors without therapeutic options

Authors

  • María Margarita Ríos-Cabrera Hospital Provincial Clínico-Quirúrgico “Arnaldo Milián Castro”, Departamento de Investigaciones, Santa Clara
  • Iraldo Bello-Rivero Centro de Ingeniería Genética y Biotecnología, Departamento de Investigaciones Clínicas, La Habana
  • Javier Cruz-Rodríguez Hospital Provincial Clínico-Quirúrgico "Arnaldo Milián Castro" https://orcid.org/0000-0002-7849-4050

DOI:

https://doi.org/10.30827/ars.v64i4.27824

Keywords:

brain tumor; interferon; clinical research

Abstract

Introduction: The poor survival of patients with high-grade malignancy brain tumors, despite the existence of some treatment options, leads to the search for new therapeutic modalities. The cuban combination of alpha and gamma interferons is novel and there is evidence that it increases the survival of patients with solid tumors.

Method: A clinical investigation was conducted to determine the efficiency of the combination in patients with high-grade brain tumors without therapeutic options. 40 patients treated at the “Arnaldo Milián Castro” Hospital in the period 2009-2020 were included, safety and efficacy were evaluated.

Results: No serious adverse events occurred, events were mild or moderate, expected, and patients recovered. After one year, 8.7 % of the cases in the experimental group had died, compared to 70.6 % in the control group. Overall survival in stage III was similar in both scenarios and in stage IV it was higher for the experimental group. The chance of survival for the patients who were treated with the combination of interferons was 0.887 times higher than the control cases. There were significant differences in functional capacity between both groups of patients.

Conclusions: It was evidenced that the Cuban combination of interferons is safe and effective for the treatment of high-grade malignancy brain tumors without therapeutic options, which makes it an efficient option in this clinical scenario.

Downloads

Download data is not yet available.

References

Sung H, Ferlay J, Siegel R L, Laversanne M, Soerjomataram I, Jema A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3): 209-249. doi:10.3322/caac.21660

Díaz J, Reyes M, Rodríguez L, Sierra E. Medios diagnósticos y tratamientos actuales del glioblastoma multiforme. Progaleno. 2020; 3(2): 87-102. doi:revprogaleno.sld.cu/index.php/progaleno/article/view/165

Lukas R, Wainwright D, Ladomersky E, Sachdev S, Sonabend A, Stupp R. Diagnosed Glioblastoma: A Review on Clinical Management. Oncology (Williston Park). 2019; 33(3):91-100. doi:europepmc.org/articles/PMC7278092

You S, Hara A, Kanayama T, Noguchi K, Niwa A, Miyai M, et al. Treatment Strategies Based on Histological Targets against Invasive and Resistant Glioblastoma. J oncol. 2019; 3(2): 1-10. doi:10.1155/2019/2964783

Schenk R. Neuroonkologische therapiekonzepte zur behandlung von astrozytomen hoheren malignitatsgrades und rezidivlokalisation. [Tesis Doctoral]. Alemania: Universidad Ratisbona; 2019. Disponible en: https://epub.uniregensburg.de/40710/1/Neuroonkologische%20Therapiekonzepte%20Astrozytom%20und%20Rezidivlokalisation%28ohne%20CV%29.pdf

Ocampo MI, Gómez JC, Feo OH. Epidemiología y caracterización general de los tumores cerebrales primarios en el adulto. Universitas medica; 60(1): 47-60. doi:10.11144/javeriana.umed60-1.cere.

Comas AS. Glioblastoma tras radioterapia: estudio de la supervivencia y del patrón de recaída en relación con la localización de la lesión respecto a la zona subventricular y la dosis de radiación recibida en dicha área. [Tesis Doctoral] España: Universidad Autónoma de Barcelona; 2018. Disponible en: https://dialnet.unirioja.es/servlet/tesis?codigo=271553

Bruna J, Alemany M. Perspectiva histórica de los estudios con mayor impacto en el tratamiento de los gliomas. Rev neurol. 2020; 70(06): 220-230. doi:10.33588/rn.7006.2019144

Wang J, Hu G, Quan X. Analysis of the Factors Affecting the Prognosis of Glioma Patients. Open Med 2019; 14: 331-335. doi:10.1515/med-2019-0031

Requena C, Alsina M, Morgado-Carrasco D, Cruz J, Sanmartín O, Serra-Guillén C, et al. Sarcoma de Kaposi y angiosarcoma cutáneo: directrices para el diagnóstico y tratamiento. Actas Dermosifiliogr 2018; 109(10): 878-887. doi:10.1016/j.ad.2018.06.013

Peña JA, Aguilar J, Alcivar LM, Álvarez JL, Anaya I, Añorve E, et al. Consenso Mexicano de Mieloma Múltiple. Gac Med Mex. 2020; 156(2): 1-49. doi:10.24875/gmm.m20000392.

Hernández J, Roque A. Interferones y SARS-CoV-2. Boletín Científico del CIMEQ. Actualización médica del SARS-CoV-2. 2020; 1(8): 6-7 Disponible en: http://files.sld.cu/cimeq/files/2020/05/Bol-CCimeq-2020-1-8-pag6-7.pdf

Sallard E, Lescure FX, Yazdanpanah Y, Mentre F, Peiffer-Smadja N. Type 1 interferons as a potential treatment against COVID-19. Antiviral res. 2020; 178(104791): 1-4. doi:10.1016/j.antiviral.2020.104791

Hao Q, Tang H. Interferon-γ and Smacmimetics synergize to induce apoptosis of lung cancer cells in a TNFα-independent manner. Cancer cell int. 2018; 18(84): 1-12. doi:10.1186/s12935-018-0579-y

rd Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2018). JITC 2018; 6(115): doi:10.1186/s40425-018-0423-x

Deng S, Zhang G, Kuai J, Fan P, Wang X, Zhou P, et al. Lentinan inhibits tumor angiogenesis via interferon γ and in a T cell independent manner. J Exp Clin Cancer Res. 2018; 37(260): 1-12. doi:10.1186/s13046-018-0932-y

Green D, Nunes A, David-Ocampo V, Ekwede I, Houston N, Highfill S, et al. A Phase 1 trial of autologous monocytes stimulated ex vivo with Sylatron® (Peginterferon alfa-2b) and Actimmune® (Interferon gamma-1b) for intra-peritoneal administration in recurrent ovarian cancer. J Transl Med. 2018; 16(1): 196. doi:10.1186/s12967-018-1569-5

Provance OK, Lewis-Wambi J. Deciphering the role of interferon alpha signaling and microenvironment crosstalk in inflammatory breast cancer. Breast Cancer Res 2019; 21(59): 1-10. doi:10.1186/s13058-019-1140-1

Lu C, Klement J, Ibrahim M, Xiao W, Redd P, Nayak-Kapoo A, et al. Type I interferon suppresses tumor growth through activating the STAT3-granzyme B pathway in tumor-infiltrating cytotoxic T lymphocytes. J Immunother Cancer 2019; 7(157): 1-11. doi:10.1186/s40425-019-0635-8

Green DS, Nunes AT, David-Ocampo V, Ekwede IB, Houston ND, Highfill SL, et al. A Phase 1 trial of autologous monocytes stimulated ex vivo with Sylatron® (Peginterferon alfa-2b) and Actimmune® (Interferon gamma-1b) for intra-peritoneal administration in recurrent ovarian cancer. J Transl Med. 2018; 16(196): 1-9. doi:10.1186/s12967-018-1569-5

Resumen de las Características del Producto HeberFERON® (Interferón alfa 2b hu-rec + Interferón gamma hu-rec) [Internet].Registro Sanitario de Medicamentos, Centro para el Control Estatal de Medicamentos, Equipos y Dispositivos Médicos CECMED. 2017; Disponible en: https://www.cecmed.cu/registro/rcp/biologicos/heberferonr-interferon-alfa-2b-hu-rec-interferon-gamma-hu-rec

Wahner HCW, Träger M, Bender K, Schweizer L, Onken J, Senger C, et al. Predicting survival in anaplastic astrocytoma patients in a single-center cohort of 108 patients. Radiat Oncol. 2020; 15(282): 1-9. doi:10.1186/s13014-020-01728-8

Christians A, Adel-Horowski A, Banan R, Lehmann U, Bartels S, Behling F, et al. The prognostic role of IDH mutations in homogeneously treated patients with anaplastic astrocytomas and glioblastomas. Acta Neuropathol Commun. 2019; 7(156): 1-11 doi:10.1186/s40478-019-0817-0

Wu J, Yuan Y, Long Priel DA, Fink D, Peer CJ, Sissung TM, et al. Phase I Study of Zotiraciclib in Combination with Temozolomide for Patients with Recurrent High-grade Astrocytomas. Clin Cancer Res. 2021; 27(12) 3298-3306. doi:10.1158/1078-0432.CCR-20-4730

Cloughesy TF, Petrecca K, Walbert T, Butowski N, Salacz M, Perry J, et al. Effect of Vocimagene Amiretrorepvec in Combination With Flucytosinevs Standard of Care on Survival Following Tumor Resection in Patients With Recurrent High-Grade Glioma: A Randomized Clinical Trial. JAMA Oncol 2020 6(12): 1939-1946. doi:10.1001/jamaoncol.2020.3161

Shieh L, Guo H, Ho C, Lin L, Chang C, Ho S Survival of glioblastoma treated with a moderately escalated radiation dose-Results of a retrospective analysis. PloS one 2020 15(5): 1-14 doi:10.1371/journal.pone.0233188

Eun J, Sung H, Young S, Chai S, Hoon J, Heo H. Identification of Early Response to Anti-Angiogenic Therapy in Recurrent Glioblastoma: Amide Proton Transfer–weighted and Perfusion-weighted MRI compared with Diffusion-weighted MRI. Radiology 2020 295(2): 397-406 doi:10.1148/radiol.2020191376

Kumar G, DSouza H, Menon N, Srinivas S, Vallathol DH, Boppana M, et al. Safety and efficacy of bevacizumab biosimilar in recurrent/ progressive glioblastoma. Ecancermedicalscience, 2021 15(1166): 1-9 doi:10.3332/ecancer.2021.1166

Biswas A. Bevacizumab in progressive or recurrent glioblastoma: A quest for the optimal dosage. Cancer Research, Statistics, and Treatment, 2021; 4: 356-359 doi: 10.4103/crst.crst_128_21

Dietterle J, Wende T, Wilhelmy F, Eisenlöffel C, Jähne K, Taubenheim S, et al. The prognostic value of peri-operative neurological performance in glioblastoma patients. Acta Neurochir, 2020; 162: 417-425 doi:10.1007/s00701-019-04136-4

Straube C, Kessel KA, Antoni S, Gempt J, Meyer B, Schlegel J, et al. A balanced score to predict survival of elderly patients newly diagnosed with glioblastoma. Radiat Oncol 2020; 15(97): 1-16 doi:10.1186/s13014-020-01549-9

Pierscianek D, Ahmadipour Y, Kaier K, Darkwah Oppong M, Michel A, et al. The SHORT Score for Preoperative Assessment of the Risk for Short-Term Survival in Glioblastoma. World neurosurg 2020; 138: e370-e380 doi:10.1016/j.wneu.2020.02.131

Seystahl K, Hentschel B, Loew S, Gramatzki D, Felsberg J, Herrlinger U, et al. Bevacizumab versus alkylating chemotherapy in recurrent glioblastoma. J Cancer Res Clin Oncol. 2020 146: 659-670 doi:10.1007/s00432-019-03086-9

Omuro A, Vlahovic G, Lim M, Sahebjam S, Baehring J, Cloughesy T, et al. Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: results from exploratory phase I cohorts of Check Mate 143. Neuro Oncol 2018 20(5): 674-686 doi:10.1093/neuonc/nox208

Reardon DA, Brandes AA, Omuro A, Mulholland P, Lim M, Wick A, et al. Effect of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma: The Check Mate 143 Phase 3 Randomized Clinical Trial. JAMA oncol, 2020 6(7): 1003-1010 doi:10.1001/jamaoncol.2020.1024

Nayak L, Molinaro AM, Peters K, Clarke JL, Jordan JT, Groot J, et al. Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma. Clin Cancer Res. 2021 27(4): 1048-1057 doi:10.1158/1078-0432.CCR-20-2500

Groot J, Penas-Prado M, Alfaro-Munoz K, Hunter K, Pei BL, O’Brien B, et al. Window-of-opportunity clinical trial of pembrolizumab in patients with recurrent glioblastoma reveals predominance of immune-suppressive macrophages. Neuro Oncol 2020 22(4): 539-549 doi:10.1093/neuonc/noz185

Detti B., Scoccianti S., Teriaca M.A., Maragna V., Lorenzetti V., Lucidi S., et.al. Bevacizumab in recurrent high-grade glioma: a single institution retrospective analysis on 92 patients. Radiol Med. 2021; 126: 1249-1254 doi:10.1007/s11547-021-01381-5

Reardon DA, Kim TM, Frenel JS, Simonelli M, Lopez J, Subramaniam DS, et al. Treatment with pembrolizumab in programmed death ligand 1-positive recurrent glioblastoma: Results from the multicohort phase 1 KEYNOTE-028 trial. Cancer 2021 127(10): 1620-1629 doi:10.1002/cncr.33378

Li L, Jiangchao H, Haipeng X., Xiangyang Z. Efficacy and safety of dendritic cell vaccines for patients with glioblastoma: A meta-analysis of randomized controlled trials. Int Immunopharmacol. 2020; 83: 106336 doi:10.1016/j.intimp.2020.106336

Duncan Y, Garcia Y, Collazo S, Rodríguez M, Zalazar M, Rodríguez J, et al. Five years follow-up of patients with non-melanoma skin cancer treated with HeberFERON. medRxiv. 2022; doi:10.1101/2022.02.07.22270604

Esquivel I, Pérez J, Duncan Y, Vázquez D, Bequet M, Báez L, et. al. Effect and safety of combination of interferon alpha-2b and gamma or interferon alpha-2b for negativization of SARS-CoV-2 viral RNA. Preliminary results of a randomized controlled clinical trial. medRxiv 2020; 07: doi:10.1101/2020.07.29.20164251

Viada CE, Lima M, Soriano JL, Fors MM, Santiesteban Y, Santiesteban Y, et al. Meta-análisis de ensayos clínicos controlados de Nimotuzumab combinado con quimiorradioterapia en cáncer esofágico avanzado. Rev Cub Oncol. 2021; 19(3): 1-23 Disponible en: http://www.revoncologia.sld.cu/index.php/onc/article/view/148

Alvarez M, Saurez G, Viada C, Luaces P, Frías A, Santiesteban Y, et. al. Nimotuzumab en el tratamiento de pacientes con glioma ma-ligno. Comparación entre estudios pre-registro y pos-aprobación. Bionatura 2016; 1(4) 171-176 doi:10.21931/RB/2016.01.04.3

Saurez MG, Salva CSN, Piedra SP, Iglesias CB, Toledo JC, Solomón MT, et al. Security and effectiveness of nimotuzumab in patients with malign glial tumors. Rev Cubana Neurol Neurocir. 2015; 5(2): 123-132 Disponible en: http://www.revneuro.sld.cu/index.php/neu/article/view/240

Published

2023-09-22

How to Cite

1.
Ríos-Cabrera MM, Bello-Rivero I, Cruz-Rodríguez J. Combination of interferons in patients with high-grade brain tumors without therapeutic options. Ars Pharm [Internet]. 2023 Sep. 22 [cited 2025 Apr. 3];64(4):315-28. Available from: https://revistaseug.ugr.es/index.php/ars/article/view/27824

Issue

Section

Original Articles