Trial reportBMC cancer2012
Dynamic tumor modeling of the dose-response relationship for everolimus in metastatic renal cell carcinoma using data from the phase 3 RECORD-1 trial.
Trial report in BMC cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00410124 (A Randomized, Double-blind, Placebo-controlled, Multicenter Phase III Study to Compare the Safety and Efficacy of RAD001 Plus Best Supportive Care), which is not on this map. Cited by 18 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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 Randomized, Double-blind, Placebo-controlled, Multicenter Phase III Study to Compare the Safety and Efficacy of RAD001 Plus Best Supportive Care (BSC) Versus BSC Plus Placebo in Patients With Metastatic Carcinoma of the Kidney Which Has Progressed on VEGF Receptor Tyrosine Kinase Inhibitor
Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Skipping a pillar does not make for strong foundations: Pharmacokinetic-pharmacodynamic reasoning behind the shape of dose-response relationships in oncology.CPT: pharmacometrics & systems pharmacology · 2023Pooled it
- Modeling Tumor Growth Using Partly Conditional Survival Models: A Case Study in Colorectal Cancer.JCO clinical cancer informatics · 2023Trial
- Quantitative Method for Monitoring Tumor Evolution During and After Therapy.Journal of personalized medicine · 2025Article
- Model-Informed Dose Optimization of Pazopanib in Real-World Patients with Cancer.Clinical pharmacokinetics · 2025Article
- Semi-mechanistic efficacy model for PARP + ATR inhibitors-application to rucaparib and talazoparib in combination with gartisertib in breast cancer PDXs.British journal of cancer · 2025Article
- Mathematical and Machine Learning Models of Renal Cell Carcinoma: A Review.Bioengineering (Basel, Switzerland) · 2023Review
- Mechanistic characterization of oscillatory patterns in unperturbed tumor growth dynamics: The interplay between cancer cells and components of tumor microenvironment.PLoS computational biology · 2023Article
- Tumor growth inhibition modeling to support the starting dose for dacomitinib.CPT: pharmacometrics & systems pharmacology · 2022Article
- A Review of Mathematical Models for Tumor Dynamics and Treatment Resistance Evolution of Solid Tumors.CPT: pharmacometrics & systems pharmacology · 2019Review
- Dosage adjustments in pivotal clinical trials with oral targeted therapies in solid tumors conducted in Europe.European journal of clinical pharmacology · 2019Article
- Population Pharmacokinetic/Pharmacodynamic Modeling of Tumor Size Dynamics in Pembrolizumab-Treated Advanced Melanoma.CPT: pharmacometrics & systems pharmacology · 2017Article
- A Review of Modeling Approaches to Predict Drug Response in Clinical Oncology.Yonsei medical journal · 2017Review
- Preclinical Modeling of Tumor Growth and Angiogenesis Inhibition to Describe Pazopanib Clinical Effects in Renal Cell Carcinoma.CPT: pharmacometrics & systems pharmacology · 2015Article
- Molecular Connections between Cancer Cell Metabolism and the Tumor Microenvironment.International journal of molecular sciences · 2015Review
- Population pharmacokinetic-pharmacodynamic modelling in oncology: a tool for predicting clinical response.British journal of clinical pharmacology · 2015Review
- A review of mixed-effects models of tumor growth and effects of anticancer drug treatment used in population analysis.CPT: pharmacometrics & systems pharmacology · 2014Article
- Article
- Pembrolizumab plus Lenvatinib for Synchronous Triple Primary Malignancies of the Kidney, Bladder, and Liver: Clinical Implications of Conflict of Drug Doses and Dominant Tumor Biology.Case reports in oncologyArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe phase 3 RECORD-1 trial (NCT00410124) established the efficacy and safety of everolimus in patients with metastatic renal cell carcinoma (mRCC) who progress on sunitinib or sorafenib. In RECORD-1, patients received 10 mg everolimus daily, with dose reduction to 5 mg daily allowed for toxicity. We have developed a model of tumor growth dynamics utilizing serial measurements of the sum of the longest tumor diameters (SLD) from individual RECORD-1 patients to define the dose-response relationship of everolimus.
resultsThe model predicts that after 1 year of continuous dosing, the change in SLD of target lesions will be +142.1% ± 98.3%, +22.4% ± 17.2%, and -15.7% ± 11.5% in the average patient treated with placebo, 5 mg everolimus, and 10 mg everolimus, respectively. This nonlinear, mixed-effects modeling approach can be used to describe the dynamics of each individual patient, as well as the overall population. This allows evaluation of how an actual dosing history and individual covariates impact on the observed drug effect, and offers the possibility of predicting clinical observations as a function of time.
conclusionsIn this pharmacodynamic model of tumor response, everolimus more effectively shrinks target lesions in mRCC when dosed 10 mg daily versus 5 mg daily, although a 5-mg dose still shows an antitumor effect. These data support earlier studies that established 10 mg daily as the preferred clinical dose of everolimus, and improve our understanding of the everolimus dose-response relationship.
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What OpenQuestion holds
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.