Trial reportBritish journal of clinical pharmacology2016
Pharmacokinetics and pharmacodynamics of everolimus in patients with renal angiomyolipoma and tuberous sclerosis complex or lymphangioleiomyomatosis.
Trial report in British journal of clinical pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- The efficacy and adverse events of mTOR inhibitors in lymphangioleiomyomatosis: systematic review and meta-analysis.Orphanet journal of rare diseases · 2018Pooled it
- Pharmacokinetics and pharmacodynamics of everolimus in patients with renal angiomyolipoma and tuberous sclerosis complex or lymphangioleiomyomatosis.British journal of clinical pharmacology · 2016Trial
- CCL14, identified by multi-omics approach, serves as a novel indicator of disease severity and progression in lymphangioleiomyomatosis.Orphanet journal of rare diseases · 2026Article
- Associations of VEGF-D levels with clinical manifestations in lymphangioleiomyomatosis: a cross-sectional analysis of 631 cases.Orphanet journal of rare diseases · 2025Article
- Distinct peripheral pro-inflammatory profile associated with tuberous sclerosis complex and epilepsy.Epilepsia · 2025Article
- New staging criteria predicting m-tor inhibitors treatment effect of renal angiomyolipoma in tuberous sclerosis complex patients.World journal of urology · 2024Article
- Clinical practice recommendations for kidney involvement in tuberous sclerosis complex: a consensus statement by the ERKNet Working Group for Autosomal Dominant Structural Kidney Disorders and the ERA Genes & Kidney Working Group.Nature reviews. Nephrology · 2024Review
- Pilot study evaluating everolimus molecular mechanisms in tuberous sclerosis complex and focal cortical dysplasia.PloS one · 2022Article
- Impact of BMI on the outcome of metastatic breast cancer patients treated with everolimus: a retrospective exploratory analysis of the BALLET study.Oncotarget · 2020Article
- Elevated plasma tyrosine kinases VEGF-D and HER4 in heart failure patients decrease after heart transplantation in association with improved haemodynamics.Heart and vessels · 2020Article
- Synergistic Highly Potent Targeted Drug Combinations in Different Pheochromocytoma Models Including Human Tumor Cultures.Endocrinology · 2019Article
- CT characteristics predict the response to everolimus or sirolimus of renal angiomyolipomas in patients with tuberous sclerosis complex.International urology and nephrology · 2019Article
- A novel mouse model of hemangiopericytoma due to loss of Tsc2.Human molecular genetics · 2018Article
- The role of GSK3 and its reversal with GSK3 antagonism in everolimus resistance.Endocrine-related cancer · 2018Article
- Genomics in neurodevelopmental disorders: an avenue to personalized medicine.Experimental & molecular medicine · 2018Review
- Tsc2 disruption in mesenchymal progenitors results in tumors with vascular anomalies overexpressingeLife · 2017Article
- Treatment of renal angiomyolipoma in tuberous sclerosis complex (TSC) patients.Pediatric nephrology (Berlin, Germany) · 2017Review
- Article
- Management of everolimus-associated adverse events in patients with tuberous sclerosis complex: a practical guide.Orphanet journal of rare diseases · 2017Review
- Everolimus safety and efficacy for renal angiomyolipomas associated with tuberous sclerosis complex: a Spanish expanded access trial.Orphanet journal of rare diseases · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 7 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsThe purpose was to determine the exposure-response relationship of everolimus in patients with angiomyolipoma from the EXIST-2 trial and to analyze the correlation between exposure and plasma concentrations of angiogenic biomarkers in these patients.
methodsOne hundred and eighteen patients with angiomyolipoma associated with tuberous sclerosis complex (TSC) or sporadic lymphangioleiomyomatosis (sLAM) were randomly assigned 2 : 1 to receive everolimus 10 mg (n = 79) or placebo (n = 39) once daily. Blood samples for determining everolimus concentration were collected at weeks 2, 4, 12, 24 and 48 during double-blind treatment. Plasma samples for biomarker analysis were collected at baseline and weeks 4, 12, 24, 36, 48 and at the end of treatment. Concentrations of eight angiogenic biomarkers associated with tumour growth were determined by enzyme-linked immunosorbent assay (ELISA).
resultsPeak and trough concentrations of everolimus in blood remained stable over time and similar to those reported in other indications. Substantial pharmacodynamic effects were observed in the everolimus, but not placebo, arm for three biomarkers: After 24 weeks of treatment, reduction of vascular endothelial growth factor D (VEGF-D) and collagen type IV (COL-IV) (mean fold-changes with 95% confidence intervals [CI] were 0.36 [0.33, 0.40], and 0.54 [0.51, 0.57], respectively, P < 0.001 for both), along with increased VEGF-A (mean fold-change of 1.59 [1.39, 1.80], P < 0.001), were seen. Furthermore, baseline VEGF-D and COL-IV levels were associated with angiomyolipoma size at baseline and with angiomyolipoma response to everolimus.
conclusionsThese findings suggest that plasma angiogenic markers may provide an objective measure of patient response to everolimus.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.