PMID- 26156073
OWN - NLM
STAT- MEDLINE
DCOM- 20160816
LR  - 20220330
IS  - 1460-2385 (Electronic)
IS  - 0931-0509 (Linking)
VI  - 31
IP  - 1
DP  - 2016 Jan
TI  - Everolimus for renal angiomyolipoma in patients with tuberous sclerosis complex 
      or sporadic lymphangioleiomyomatosis: extension of a randomized controlled trial.
PG  - 111-9
LID - 10.1093/ndt/gfv249 [doi]
AB  - BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: 
      clinicaltrialsgov identifier: NCT00790400 
      (http://clinicaltrials.gov/ct2/show/NCT00790400).
CI  - (c) The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. 
      All rights reserved.
FAU - Bissler, John J
AU  - Bissler JJ
AD  - St. Jude Children's Research Hospital and Le Bonheur Children's Hospital, 
      University of Tennessee Health Science Center, Memphis, TN, USA.
FAU - Kingswood, John Christopher
AU  - Kingswood JC
AD  - Royal Sussex County Hospital, Brighton, UK.
FAU - Radzikowska, Elzbieta
AU  - Radzikowska E
AD  - National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland.
FAU - Zonnenberg, Bernard A
AU  - Zonnenberg BA
AD  - Universitair Medisch Centrum, Utrecht, The Netherlands.
FAU - Frost, Michael
AU  - Frost M
AD  - Minnesota Epilepsy Group, St Paul, MN, USA.
FAU - Belousova, Elena
AU  - Belousova E
AD  - Moscow Research Institute of Pediatrics and Pediatric Surgery, Moscow, Russia.
FAU - Sauter, Matthias
AU  - Sauter M
AD  - Medizinische Klinik und Poliklinik IV, Klinikum der Universitat MuNchen, Munich, 
      Germany.
FAU - Nonomura, Norio
AU  - Nonomura N
AD  - Osaka University Hospital, Osaka, Japan.
FAU - Brakemeier, Susanne
AU  - Brakemeier S
AD  - Charite Universitatsmedizin, Berlin, Germany.
FAU - de Vries, Petrus J
AU  - de Vries PJ
AD  - Division of Child and Adolescent Psychiatry, University of Cape Town, Cape Town, 
      South Africa.
FAU - Berkowitz, Noah
AU  - Berkowitz N
AD  - Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
FAU - Miao, Sara
AU  - Miao S
AD  - Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
FAU - Segal, Scott
AU  - Segal S
AD  - Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
FAU - Peyrard, Severine
AU  - Peyrard S
AD  - Novartis Pharmaceuticals S.A.S., Rueil-Malmaison, France.
FAU - Budde, Klemens
AU  - Budde K
AD  - Charite Universitatsmedizin, Berlin, Germany.
LA  - eng
SI  - ClinicalTrials.gov/NCT00790400
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20150708
PL  - England
TA  - Nephrol Dial Transplant
JT  - Nephrology, dialysis, transplantation : official publication of the European 
      Dialysis and Transplant Association - European Renal Association
JID - 8706402
RN  - 0 (Antineoplastic Agents)
RN  - 9HW64Q8G6G (Everolimus)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Angiomyolipoma/*drug therapy/pathology
MH  - Antineoplastic Agents/*therapeutic use
MH  - Disease-Free Survival
MH  - Double-Blind Method
MH  - Everolimus/*therapeutic use
MH  - Female
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Kidney/pathology
MH  - Kidney Neoplasms/*drug therapy/pathology
MH  - Lymphangioleiomyomatosis/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Treatment Outcome
MH  - Tuberous Sclerosis/*drug therapy
MH  - Tumor Burden/drug effects
MH  - Young Adult
OTO - NOTNLM
OT  - everolimus
OT  - mTOR inhibitors
OT  - renal angiomyolipoma
OT  - sporadic lymphangioleiomyomatosis
OT  - tuberous sclerosis complex
EDAT- 2015/07/15 06:00
MHDA- 2016/08/17 06:00
CRDT- 2015/07/10 06:00
PHST- 2014/12/02 00:00 [received]
PHST- 2015/05/11 00:00 [accepted]
PHST- 2015/07/10 06:00 [entrez]
PHST- 2015/07/15 06:00 [pubmed]
PHST- 2016/08/17 06:00 [medline]
AID - gfv249 [pii]
AID - 10.1093/ndt/gfv249 [doi]
PST - ppublish
SO  - Nephrol Dial Transplant. 2016 Jan;31(1):111-9. doi: 10.1093/ndt/gfv249. Epub 2015 
      Jul 8.