Hydroxyurea for the Treatment of Recurrence and Unresectable Meningiomas: A Systematic Review

Dirga Rachmad Aprianto; Rahadian Indarto Susilo; Joni Wahyuhadi; Irwan Barlian Immadoel Haq

doi:10.3889/oamjms.2021.5596

Authors

Dirga Rachmad Aprianto Department of Neurosurgery, Dr. Soetomo Academic General Hospital, Faculty of Medicine, Airlangga University, Surabaya, Indonesia
Rahadian Indarto Susilo Department of Neurosurgery, Dr. Soetomo Academic General Hospital, Faculty of Medicine, Airlangga University, Surabaya, Indonesia
Joni Wahyuhadi Department of Neurosurgery, Dr. Soetomo Academic General Hospital, Faculty of Medicine, Airlangga University, Surabaya, Indonesia
Irwan Barlian Immadoel Haq Department of Neurosurgery, Dr. Soetomo Academic General Hospital, Faculty of Medicine, Airlangga University, Surabaya, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2021.5596

Keywords:

Meningioma, Hydroxyurea, unresectable meningioma, recurrence, progression free survival

Abstract

BACKGROUND: Meningioma is mostly benign tumor (World Health Organization Grade 1) and surgery remains the best option in treating symptomatic or enlarging meningiomas where total removal of the tumor is the goal of surgery. Radiation therapy has shown to be effective to cease the growth of the tumor, but not in tumor regression. Adjuvant therapy may treat patients with recurrence or unresectable meningiomas yet the uses of hormone therapy, immunotherapy, or chemotherapy had many results and were not consistently effective. Hydroxyurea has promising results in patients with meningiomas.

AIM: This study analyzed the efficacy and safety of hydroxyurea for the treatments of recurrence or unresectable meningiomas.

MATERIALS AND METHODS: The study adapted PRISMA guidelines by searching electronic databases, PUBMED, Cochrane, and JNS in August 2020 and was full-text observational study or randomized control trial presented as PICO and assessed using the risk-of-bias assessment tool.

RESULTS: A total of six articles (157 patients with meningioma) were reviewed from the total of 425. Hydroxyurea was administered orally for 28 days continuously and repeated every 28 days or after recovery with various dosages in six studies.

DISCUSSION: Administration of hydroxyurea showed a varied stable disease rate ranging from 30 to 69% with a median progression-free survival med varying between 2 and 27.75 months. The studies performed oral hydroxyurea administration at a dose of 20–30 mg/kg body weight/day or 1000 mg/m2/day. However, the adverse events (AEs) that appear also, based on literature, are not much different from other chemotherapy administrations.

CONCLUSION: Patients with unresected and recurrent meningiomas have limited treatment options due to difficulty for surgical management. However, this study offers another perspective addressing the efficacy and safety results with the use of hydroxyurea. Overall, hydroxyurea showed good outcomes, particularly in low-grade meningioma, with relatively low AEs. Further combination treatment may be used as a multimodal therapy.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Ostrom QT, Gittleman H, Farah P, Ondracek A, Chen Y, Wolinsky Y, et al. CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2006-2010. Neuro Oncol. 2013;15 (Suppl 2):ii1-56. https://doi.org/10.1093/neuonc/not151 PMid:24137015

Engelhard HH, Villano JL, Porter KR, Stewart AK, Barua M, Barker FG, et al. Clinical presentation, histology, and treatment in 430 patients with primary tumors of the spinal cord, spinal meninges, or cauda equina. J Neurosurg Spine. 2010;13(1):67- 77. https://doi.org/10.3171/2010.3.spine09430 PMid:20594020

Al-Mefty O, Kadri PA, Pravdenkova S, Sawyer JR, Stangeby C, Husain M. Malignant progression in meningioma: Documentation of a series and analysis of cytogenetic findings. J Neurosurg. 2004;101(2):210-8. https://doi.org/10.3171/jns.2004.101.2.0210 PMid:15309910

Apra C, Peyre M, Kalamarides M. Current treatment options for meningioma. Expert Rev Neurother. 2018;18(3):241-9. https://doi.org/10.1080/14737175.2018.1429920 PMid:29338455

Rogers L, Barani I, Chamberlain M, Kaley TJ, McDermott M, Raizer J, et al. Meningiomas: Knowledge base, treatment outcomes, and uncertainties. A RANO review. J Neurosurg. 2015;122(1):4-23. https://doi.org/10.3171/2014.7.jns131644 PMid:25343186

Grunberg SM, Weiss MH, Spitz IM, Ahmadi J, Sadun A, Russel CA, et al. Treatment of unresectable meningiomas with the antiprogesterone agent mifepristone. J Neurosurg. 1991;74(6):861-6. https://doi.org/10.3171/jns.1991.74.6.0861 PMid:2033444

Ortolá Buigues A, Crespo Hernández I, Jorquera Moya M, Díaz Pérez JÁ. Unresectable recurrent multiple meningioma: A case report with radiological response to somatostatin analogues. Case Rep Oncol. 2016;9(2):520-5. https://doi.org/10.1159/000448212 PMid:27721778

Mason WP, Gentili F, MacDonald DR, Hariharan S, Cruz CR, Abrey LE. Stabilization of disease progression by hydroxyurea in patients with recurrent or unresectable meningioma. J Neurosurg. 2002;97(2):341-6. https://doi.org/10.3171/jns.2002.97.2.0341 PMid:12186462

Hahn BM, Schrell UM, Sauer R, Fahlbusch R, Ganslandt O, Grabenbauer GG. Prolonged oral hydroxyurea and concurrent 3d-conformal radiation in patients with progressive or recurrent meningioma: Results of a pilot study. J Neurooncol. 2005;74(2):157-65. https://doi.org/10.1007/s11060-004-2337-3 PMid:16193387

Reardon DA, Norden AD, Desjardins A, Vredenburgh JJ, Herndon JE, Coan A, et al. Phase II study of Gleevec® plus hydroxyurea (HU) in adults with progressive or recurrent meningioma. J Neurooncol. 2012;106(2):409-15. https://doi.org/10.1007/s11060-011-0687-1 PMid:21938530

Kim MS, Yu DW, Jung YJ, Kim SW, Chang CH, Kim OL. Longterm follow-up result of hydroxyurea chemotherapy for recurrent meningiomas. J Korean Neurosurg Soc. 2012;52(6):517-22. https://doi.org/10.3340/jkns.2012.52.6.517 PMid:23346322

Newton HB. Hydroxyurea chemotherapy in the treatment of meningiomas. Neurosurg Focus. 2007;23(4):E11. PMid:17961035

Newton HB, Slivka MA, Stevens C. Hydroxyurea chemotherapy for unresectable or residual meningioma. J Neurooncol. 2000;49(2):165-70. PMid:11206012

Loven D, Hardoff R, Sever ZB, Steinmetz AP, Gornish M, Rappaport ZH, et al. Non-resectable slow-growing meningiomas treated by hydroxyurea. J Neurooncol. 2004;67(1-2):221-6. https://doi.org/10.1023/b:neon.0000021827.85754.8e PMid:15072471

Chamberlain MC, Johnston SK. Hydroxyurea for recurrent surgery and radiation refractory meningioma: A retrospective case series. J Neurooncol. 2011;104(3):765-71. https://doi.org/10.1007/s11060-011-0541-5 PMid:21318318

Chamberlain MC. Hydroxyurea for recurrent surgery and radiation refractory high-grade meningioma. J Neurooncol. 2012;107(2):315-21. https://doi.org/10.1007/s11060-011-0741-z PMid:22127733

Grabenbauer GG, Anders K, Fietkau RJ, Klautke G, Feldmann HJ, Weiser S, et al. Prolonged infusional topotecan and accelerated hyperfractionated 3d-conformal radiation in patients with newly diagnosed glioblastoma--a phase I study. J Neurooncol. 2002;60(3):269-75. PMid:12510778

Kim J, Kim KH, Kim YZ. The clinical outcome of hydroxyurea chemotherapy after incomplete resection of atypical meningiomas. Brain Tumor Res Treat. 2017;5(2):77-86. https://doi.org/10.14791/btrt.2017.5.2.77 PMid:29188208

Moazzam AA, Wagle N, Zada G. Recent developments in chemotherapy for meningiomas: A review. Neurosurg Focus. 2013;35(6):1-10. https://doi.org/10.3171/2013.10.focus13341

Lohrke J, Frenzel T, Endrikat J, Alves FC, Grist TM, Law M, et al. 25 years of contrast-enhanced MRI: Developments, current challenges and future perspectives. Adv Ther. 2016;33(1):1-28. https://doi.org/10.1007/s12325-015-0275-4 PMid:26809251

Sobol WT. Recent advances in MRI technology: Implications for image quality and patient safety. Saudi J Ophthalmol. 2012;26(4):393-9. https://doi.org/10.1016/j.sjopt.2012.07.005 PMid:23961024

Norden AD, Young GS, Setayesh K, Muzikansky A, Ciampa AS, Ebbeling LG, et al. Bevacizumab for recurrent malignant gliomas: Efficacy, toxicity, and patterns of recurrence. Neurology. 2008;70(10):779-87. https://doi.org/10.1212/01.wnl.0000304121.57857.38 PMid:18316689

Chamberlain MC. Bevacizumab for the treatment of recurrent glioblastoma. In: Clinical Medicine Insights: Oncology. Vol. 5. New Zealand: Libertas Academica Ltd.; 2011. p. 117-29.

Lou E, Sumrall AL, Turner S, Peters KB, Desjardins A, Vredenburgh JJ, et al. Bevacizumab therapy for adults with recurrent/progressive meningioma: A retrospective series. J Neurooncol. 2012;109(1):63-70. https://doi.org/10.1007/s11060-012-0861-0 PMid:22535433

Mitra S, Li G, Harsh GR 4th. Passive antibody-mediated immunotherapy for the treatment of malignant gliomas. Neurosurg Clin N Am. 2010;21(1):67-76. https://doi.org/10.1016/j.nec.2009.08.010 PMid:19944967