Everolimus for renal angiomyolipoma in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis: extension of a randomized controlled trial
| Autor: | Susanne Brakemeier, Klemens Budde, Bernard A. Zonnenberg, Michael Frost, Scott Segal, Matthias Sauter, John J. Bissler, J. C. Kingswood, Elena Belousova, Petrus J. de Vries, Severine Peyrard, Elżbieta Radzikowska, Noah Berkowitz, Norio Nonomura, Sara Miao |
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| Rok vydání: | 2014 |
| Předmět: |
Target lesion
Adult Male medicine.medical_specialty Angiomyolipoma Adolescent 030232 urology & nephrology Urology Antineoplastic Agents Kaplan-Meier Estimate Kidney Disease-Free Survival law.invention 03 medical and health sciences Tuberous sclerosis Young Adult 0302 clinical medicine Randomized controlled trial Double-Blind Method law Tuberous Sclerosis medicine Humans Everolimus Lymphangioleiomyomatosis Adverse effect Transplantation business.industry Middle Aged medicine.disease Kidney Neoplasms Tumor Burden Treatment Outcome Tolerability Nephrology 030220 oncology & carcinogenesis Female business medicine.drug |
| Zdroj: | Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 31(1) |
| ISSN: | 1460-2385 0079-0400 |
| Popis: | Mammalian target of rapamycin (mTOR) inhibitors are recommended as first-line treatment of renal angiomyolipoma associated with tuberous sclerosis complex (TSC) or sporadic lymphangioleiomyomatosis (sporadic LAM), but follow-up is limited. Longer term efficacy and tolerability data from a Phase 3, double-blind, placebo-controlled trial are presented.Following favorable results from the primary analysis (data cutoff 30 June 2011) of the EXIST-2 trial, patients still receiving study treatment were allowed to enter an open-label extension. Everolimus was initiated at 10 mg once daily and titrated based on tolerability. The primary outcome was angiomyolipoma response rate (≥ 50% reduction from baseline in target lesion volumes). Safety was a secondary endpoint.As of the cutoff date (1 May 2013), 112 patients had received everolimus, and the response rate in 107 patients with angiomyolipoma (median duration of medication exposure of 28.9 months) was 54%. The proportion of patients achieving angiomyolipoma reductions of ≥ 30% and ≥ 50% increased over time, reaching 81.6% (62/76) and 64.5% (49/76), respectively, by Week 96. No everolimus-treated patients experienced renal bleeding. The long-term safety profile was consistent with previous reports; adverse events (AEs) were mostly Grade 1/2, and there were no new safety issues. The frequency of emerging AEs and severe AEs lessened over time.Longer term everolimus treatment appeared safe and effective in patients with TSC- or sporadic LAM-associated renal angiomyolipoma not requiring surgical intervention. Continued reduction in angiomyolipoma volume was demonstrated, and there was no angiomyolipoma-related bleeding; AEs were predictable and generally manageable.clinicaltrialsgov identifier: NCT00790400 (http://clinicaltrials.gov/ct2/show/NCT00790400). |
| Databáze: | OpenAIRE |
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