The Effect of Everolimus on Subependymal Giant Cell Astrocytoma (SEGA) in Children with Tuberous Sclerosis Complex
Iranian Journal of Child Neurology,
Vol. 15 No. 4 (2021),
1 October 2021
https://doi.org/10.22037/ijcn.v15i4.30591
Abstract
Objective: Subependymal Giant Cell Astrocytomas (SEGAs) are slow-growing glioneuronal tumors typically found around the ventricles of the brain, particularly near the foramen of Monro in 15%-20% of patients with tuberous sclerosis complex (TSC). Surgical resection is the standard treatment for these symptomatic tumors. The mTOR inhibitor everolimus can be regarded as an alternative treatment of SEGAs due to the complications of surgery.
Materials & Methods: This pre- and post-treatment clinical trial was performed on 14 children (eight females and six males with a mean age of 10 years) previously diagnosed with TSC based on the diagnostic criteria. The subjects received oral everolimus at a dose of 3 mg/m2 for at least six months. The present study primarily aimed to specify the effect of this medication on SEGA volume change before and after treatment. Secondary objectives were to determine the effect of this drug on renal angiomyolipoma (AML), skin lesions, and seizures in TSC patients.
Results: Half of the patients had more than 30% of volume loss in SEGA; in 28.5% of them the response rate of ≥ 50% reduction in SEGA volume was achieved (P=0.01). Moreover, 92.9% of the patients had ≥ 50% decrease in the frequency of seizures (P=0.000). The response rates in AML and skin lesion were 14.2% and 50%, respectively.
Conclusion: Everolimus significantly reduced the seizure frequency and SEGA volume in the subjects, hence, a potential alternative treatment for symptomatic SEGA in TSC patients.
- Everolimus
- Subependymal Giant Cell Astrocytoma
- Tuberous Sclerosis Complex
How to Cite
References
Krueger DA, Northrup H, Roberds S, Smith, Sampson J, Korf B, et al. Tuberous sclerosis complex surveillance and management: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatric neurology. 2013;49(4):255-65.
Ng K, Ng S, Parker A. Annual review of children with tuberous sclerosis. Archives of Disease in Childhood Education and Practice.2015;100(3):114-21.
Leung AK, Robson WLM. Tuberous sclerosis complex: a review. Journal of Pediatric Health Care. 2007;21(2):108 14.
Franz DN. Everolimus in the treatment of subependymal giant cell astrocytomas,
, and pulmonary and skin lesions associated with tuberous sclerosis complex. Biologics: targets & therapy.
;7:211.
Napolioni V, Moavero R, Curatolo P. Recent in neurobiology of tuberous sclerosis complex. Brain and Development.(2):104-13.
Connolly MB, Hendson G, Steinbok P. Tuberous sclerosis complex: a review of the management
of epilepsy with emphasis on surgical aspects. Nervous System. 2006;22(8):896-908.
Franz DN, Tudor C, Leonard J, Egelhoff JC, Byars A, Valerius K, et al. Lamotrigine therapy of epilepsy in tuberous sclerosis. Epilepsia. 2001;42(7):935-40.
Curatolo P, Moavero R. mTOR inhibitorsin tuberous sclerosis complex. Current neuropharmacology. 2012;10(4):404-15.
Northrup H, Krueger DA, Roberds S, Smith K, Sampson J, Korf B, et al. Tuberous
sclerosis complex diagnostic criteria update: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatric neurology. 2013;49(4):243-54.
Trelinska J, Dachowska I, Baranska D, Stawiski K, Kotulska K, Fendler W, et al. Maintenance therapy with everolimus for subependymal giant cell astrocytoma in patients with tuberous sclerosis (the EMINENTS study). Pediatric blood & cancer. 2017;64(6):e26347.
Appalla D, Depalma A, Calderwood S. Mammalian target of rapamycin inhibitor induced complete remission of a recurrent subependymal giant cell astrocytoma in a patient without features of tuberous sclerosis complex. Pediatric Blood & Cancer. 2016;63(7):1276-8.
Curatolo P, Bjørnvold M, Dill PE, Ferreira JC, Feucht M, Hertzberg C, et al. The role of mTOR inhibitors in the treatment of patients with tuberous sclerosis complex: evidence-based and expert opinions. Drugs. 2016;76(5):551-65.
Atkins MB, Yasothan U, Kirkpatrick P. Everolimus. Nature Publishing Group; 2009.
Krueger DA, Care MM, Holland K, Agricola K, Tudor C, Mangeshkar P, et al. Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. New England Journal of Medicine. 2010;363(19):1801-11.
Franz DN, Belousova E, Sparagana S, Bebin EM, Frost M, Kuperman R, et al. Everolimus for subependymal giant cell astrocytoma in patients with tuberous sclerosis complex: 2-year openlabel extension of the randomised EXIST-1study. The Lancet Oncology. 2014;15(13):1513-20.
Fogarasi A, De Waele L, Bartalini G, Jozwiak S, Laforgia N, Verhelst H, et al. EFFECTS: an expanded access program of everolimus for patients with subependymal giant cell astrocytoma associated with tuberous sclerosis
complex. BMC neurology. 2016;16(1):126.
Franz DN, Agricola K, Mays M, Tudor C, Care MM, Holland‐Bouley K, et al. Everolimus for subependymal giant cell astrocytoma: 5‐year final analysis. Annals of neurology. 2015;78(6):929-38.
Arroyo MS, Krueger DA, Broomall E, Stevenson CB, Franz DN. Acute management of symptomatic subependymal giant cell astrocytoma with everolimus. Pediatric neurology. 2017;72:81-5.
Franz DN, Belousova E, Sparagana S, Bebin EM, Frost MD, Kuperman R, et al. Long-term use of everolimus in patients with tuberous sclerosis complex: final results from the XIST-1 study. PLoS One. 2016;11(6).
Cai Y, Guo H, Wang W, Li H, Sun H, Shi B, et al. Assessing the outcomes of everolimus
renal angiomyolipoma associated with tuberous sclerosis complex in China: a two years trial. Orphanet journal of rare diseases. 2018;13(1):43.
Franz D, Budde K, Kingswood J, Belousova E, Sparagana S, de Vries P, et al. Effect of everolimus on skin lesions in patients treated for subependymal giant cell astrocytoma and renal angiomyolipoma: final 4‐year
results from the randomized EXIST‐1 and EXIST‐2 studies. Journal of the European
Academy of Dermatology and Venereology. 2018;32(10):1796-803.
Nabbout R, Belousova E, Benedik MP, Carter T, Cottin V, Curatolo P, et al. Epilepsy in tuberous
sclerosis complex: Findings from the TOSCA Study. Epilepsia Open. 2019;4(1):73-84.
Bissler JJ, Kingswood JC, Radzikowska E, Zonnenberg BA, Frost M, Belousova E, et al. Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis
(EXIST-2): a multicentre, randomised, doubleblind, placebo-controlled trial. The Lancet.
;381(9869):817-24.
Cappellano A, Senerchia A, Adolfo F, Paiva P, Pinho R, Covic A, et al. Successful everolimus
therapy for SEGA in pediatric patients with tuberous sclerosis complex. Child’s Nervous System. 2013;29(12):23015.
Davies DM, de Vries PJ, Johnson SR, McCartney DL, Cox JA, Serra AL, et al. Sirolimus therapy for angiomyolipoma in tuberous sclerosis and sporadic lymphangioleiomyomatosis: a phase 2 trial. Clinical cancer research. 2011;17(12):4071-81.
Kohrman MH. Emerging treatments in the management of tuberous sclerosis complex. Pediatric neurology. 2012;46(5):267-75.
Kotulska K, Chmielewski D, Borkowska J, Jurkiewicz E, Kuczyński D, Kmieć T, et al. Long-term effect of everolimus on epilepsy and growth in children under 3 years of age treated for subependymal giant cell astrocytoma associated with tuberous sclerosis complex. European Journal of Paediatric Neurology.
;17(5):479-85.
Krueger DA, Wilfong AA, Holland‐Bouley K, Anderson AE, Agricola K, Tudor C, et al. Everolimus treatment of refractory epilepsy in tuberous sclerosis complex. Annals ofneurology. 2013;74(5):679-87.
McCormack FX, Inoue Y, Moss J, Singer LG, Strange C, Nakata K, et al. Efficacy and safety of sirolimus in lymphangioleiomyomatosis. New England Journal of Medicine. 2011;364(17):1595-606.
Curatolo P, Moavero R, de Vries PJ. Neurological and neuropsychiatric aspects of tuberous sclerosis complex. The Lancet Neurology. 2015;14(7):733-45.
Wiegand G, May TW, Ostertag P, Boor R, Stephani U, Franz DN. Everolimus in tuberous sclerosis patients with intractable epilepsy: a treatment option? european journal of paediatric neurology. 2013;17(6):631-8.
Mizuguchi M, Ikeda H, Kagitani-Shimono K, Yoshinaga H, Suzuki Y, Aoki M, et al. Everolimus for epilepsy and autism spectrum disorder in tuberous sclerosis complex: EXIST-3 substudy in Japan. Brain and Development.
;41(1):1-10.
Hwang S-K, Lee J-H, Yang J-e, Lim C-S, Lee J-A, Lee Y-S, et al. Everolimus improves neuropsychiatric symptoms in a patient with tuberous sclerosis carrying a novel TSC2 mutation. Molecular brain. 2016;9(1):56.
- Abstract Viewed: 542 times