Assessing the effectiveness of rapamycin on angiomyolipoma in tuberous sclerosis : a two years trial
Cabrera-López, Cristina (Institut d'Investigació Biomèdica Sant Pau)
Martí, Teresa (Institut d'Investigació Biomèdica Sant Pau)
Català, Violeta (Institut d'Investigació Biomèdica Sant Pau)
Torres, Ferran (Institut d'Investigació Biomèdica Sant Pau)
Mateu, Silvia (Institut d'Investigació Biomèdica Sant Pau)
Ballarín Castan, José Aurelio (Institut d'Investigació Biomèdica Sant Pau)
Torra Balcells, Roser (Institut d'Investigació Biomèdica Sant Pau)
Universitat Autònoma de Barcelona

Date:	2012
Abstract:	Tuberous sclerosis (TS) is a rare autosomal dominant systemic disease with an estimated prevalence of 1/6000. Renal angiomyolipoma (AML) is a benign tumour with high morbidity frequently present in TS. The aim of the study was to test the effect of rapamycin in reducing the volume of AML in TS. Twenty four-month prospective open-label, single arm, unicentre Phases II andIII study. The primary endpoint was to evaluate the effect of treatment on the reduction of at least 50% AML volume from baseline at 24 months. The secondary endpoints were: average tumour reduction, surgical complications, skin lesions and drug safety. The study population comprised 17 patients, aged >10 years who were diagnosed with TS and had ≥1 renal AML >2 cm of diameter and had a serum creatinine < 2mg/dl and urine protein/creatinine ratio < 22. 6 mg/mmol. The trial was conducted at Fundació Puigvert. Rapamycin was given to achieve stable plasma levels between 4 and 8 ng/ml. AML volume was estimated using orthogonal measurements by MRI at baseline, 6, 12 and 24 months. Ten out of 17 patients were success responders for the main outcome −58. 8%, 95%CI: 32. 9% to 81. 6%-. After 6 months of therapy, the mean volume decrease was 55. 18% (5. 01 standard error (SE); p<0. 001) and 66. 38% (4. 41 SE; p<0. 001) at year 1. There was no significant decrease between year 1 and 2. According to RECIST criteria, all patients achieved a partial response at year 1 and all but two had already achieved this partial response after 6 months. The main analysis was performed according to the intention-to-treat principle analysis. Tumour volume was analyzed over time by means of mixed models for repeated measurement analysis. We used the baseline tumour volume as a covariate for the absolute change and percentage change from baseline data. The analysis was performed using SAS version 9. 2 software, and the level of significance was established at 0. 05 (two-sided). This study show that mTOR inhibitors are a relatively safe, efficacious and less aggressive alternative than currently available options in the management of AML in TS. EudraCT number: 2007-005978-30, ClinicalTrials. gov number: NCT0121712.
Grants:	Instituto de Salud Carlos III EC07-90025 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR-1116
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Orphanet Journal of Rare Diseases, Vol. 7 (november 2012) , p. 87, ISSN 1750-1172

DOI: 10.1186/1750-1172-7-87
PMID: 23140536

9 p, 537.7 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles