Trial reportCancer chemotherapy and pharmacology2016
Everolimus pharmacokinetics and its exposure-toxicity relationship in patients with thyroid cancer.
Trial report in Cancer chemotherapy and pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01118065 (A Phase II Study to Investigate the Efficacy of RAD001), which is not on this map. Cited by 25 papers, 1 of them a synthesis that pooled it.
What it found
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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.
A Phase II Study to Investigate the Efficacy of RAD001 (Afinitor®, Everolimus) in Patients With Irresectable Recurrent or Metastatic Differentiated, Undifferentiated (Anaplastic) and Medullary Thyroid Carcinoma
Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Pooled it
- Pharmacokinetics and safety of the antitumor drug everolimus in healthy Chinese subjects: a single-dose, open-label, randomized, two-sequence, two-period crossover, phase I bioequivalence study.Frontiers in pharmacology · 2025Trial
- A pharmacological rationale for improved everolimus dosing in oncology and transplant patients.British journal of clinical pharmacology · 2018Trial
- Pharmacokinetic Optimization of Everolimus Dosing in Oncology: A Randomized Crossover Trial.Clinical pharmacokinetics · 2018Trial
- The molecular mechanisms and potential therapeutic implications of the crosstalk between DNA methylation and metabolic reprogramming in thyroid cancer.Cell death discovery · 2026Review
- A Systematic Evaluation of the Dosing Regimens for Approved Targeted Therapies and Immune Checkpoint Inhibitors in Metastatic Renal Cell Carcinoma From a Project OPTIMUS Perspective.Journal of clinical pharmacology · 2025Review
- Application of population pharmacokinetic modeling of SVG-101 to evaluate proper dose selection.Translational and clinical pharmacology · 2025Article
- Development and Clinical Validation of Model-Informed Precision Dosing for Everolimus in Liver Transplant Recipients.ACS pharmacology & translational science · 2025Article
- Targeting autophagy in astrocytes: a potential for neurodegenerative disease intervention.Frontiers in cellular neuroscience · 2025Review
- The Efficacy of a Lower Dose of Everolimus in Patients with Advanced Neuroendocrine Tumors.Cancers · 2024Article
- Deep response to a combination of mTOR inhibitor temsirolimus and dual immunotherapy of nivolumab/ipilimumab in poorly differentiated thyroid carcinoma withFrontiers in endocrinology · 2024Review
- Therapeutic Drug Monitoring of Kinase Inhibitors in Oncology.Clinical pharmacokinetics · 2023Review
- A PK-PD model linking biomarker dynamics to progression-free survival in patients treated with everolimus and sorafenib combination therapy, EVESOR phase I trial.Cancer chemotherapy and pharmacology · 2023Article
- Population pharmacokinetics of everolimus in patients with seizures associated with focal cortical dysplasia.Frontiers in pharmacology · 2023Article
- Targeting the mTOR Pathway for the Prevention of ER-Negative Breast Cancer.Cancer prevention research (Philadelphia, Pa.) · 2022Article
- Management of Renal Angiomyolipomas in Tuberous Sclerosis Complex: A Case Report and Literature Review.Journal of clinical medicine · 2022Article
- Everolimus pharmacokinetics and exposure-response relationship in Japanese patients with advanced breast cancer.Frontiers in pharmacology · 2022Article
- Real-world pharmacokinetics and pharmacodynamics of everolimus in metastatic breast cancer.Investigational new drugs · 2021Article
- Therapeutic drug monitoring of oral targeted antineoplastic drugs.European journal of clinical pharmacology · 2021Review
- Model-Informed Precision Dosing of Everolimus: External Validation in Adult Renal Transplant Recipients.Clinical pharmacokinetics · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEverolimus is a mTOR inhibitor used for the treatment of different solid malignancies. Many patients treated with the registered fixed 10 mg dose once daily are in need of dose interruptions, reductions or treatment discontinuation due to severe adverse events. This study determined the correlation between systemic everolimus exposure and toxicity. Additionally, the effect of different covariates on everolimus pharmacokinetics (PK) was explored.
methodsForty-two patients with advanced thyroid carcinoma were treated with 10 mg everolimus once daily. Serial pharmacokinetic sampling was performed on days 1 and 15. Subsequently, a population PK model was developed using NONMEM to estimate individual PK values used for analysis of an exposure-toxicity relationship. Furthermore, this model was used to investigate the influence of patient characteristics and genetic polymorphisms in genes coding for enzymes relevant in everolimus PK.
resultsPatients who required a dose reduction (n = 18) due to toxicity at any time during treatment had significant higher everolimus exposures [mean AUC0-24 (SD) 600 (274) vs. 395 (129) µg h/L, P = 0.008] than patients without a dose reduction (n = 22). A significant association between everolimus exposure and stomatitis was found in the four-level ordered logistic regression analysis (P = 0.047). The presence of at least one TTT haplotype in the ABCB1 gene was associated with a 21 % decrease in everolimus exposure.
conclusionThe current study showed that dose reductions and everolimus-induced stomatitis were strongly associated with systemic everolimus drug exposure in patients with cancer. Our findings confirm observations from another study in patients with cancer and show us that everolimus is a good candidate for individualized dosing in patients with cancer. CLINICALTRIAL. GOV NUMBER: NCT01118065.
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Registered trials
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.