ArticleCancer2012
Phase 1 trial of everolimus plus sunitinib in patients with metastatic renal cell carcinoma.
Article in Cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 2 of them syntheses 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
59 citing papers in PubMed, 2 syntheses or guidelines pooled it, 125 citations in OpenAlex.
- Pooled it
- Benefit, Risk, and Outcomes in Drug Development: A Systematic Review of Sunitinib.Journal of the National Cancer Institute · 2016Pooled it
- Everolimus with or without bevacizumab in advanced pNET: CALGB 80701 (Alliance).Endocrine-related cancer · 2022Trial
- Trial
- Metronomic cyclophosphamide attenuates mTOR-mediated expansion of regulatory T cells, but does not impact clinical outcome in patients with metastatic renal cell cancer treated with everolimus.Cancer immunology, immunotherapy : CII · 2019Trial
- Phase II Trial and Correlative Genomic Analysis of Everolimus Plus Bevacizumab in Advanced Non-Clear Cell Renal Cell Carcinoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2016Trial
- A phase I/II study of lenalidomide in combination with sunitinib in patients with advanced or metastatic renal cell carcinoma.Annals of oncology : official journal of the European Society for Medical Oncology · 2014Trial
- Article
- An Update on Novel Pharmacotherapies for the Treatment of Neuroendocrine Tumors.International journal of molecular sciences · 2025Review
- A real-world disproportionality analysis of Everolimus: data mining of the public version of FDA adverse event reporting system.Frontiers in pharmacology · 2024Article
- Adverse renal outcomes following targeted therapies in renal cell carcinoma: a systematic review and meta-analysis.Frontiers in pharmacology · 2024Review
- Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease.Signal transduction and targeted therapy · 2023Review
- Therapeutic Targeting of Cancer Stem Cells Prevents Resistance of Colorectal Cancer Cells to MEK Inhibition.ACS pharmacology & translational science · 2022Article
- Molecular Mechanisms of Resistance to Immunotherapy and Antiangiogenic Treatments in Clear Cell Renal Cell Carcinoma.Cancers · 2021Review
- Vorolanib (X-82), an oral anti-VEGFR/PDGFR/CSF1R tyrosine kinase inhibitor, with everolimus in solid tumors: results of a phase I study.Investigational new drugs · 2021Article
- Cardiovascular Toxicities of Antiangiogenic Tyrosine Kinase Inhibitors: A Retrospective, Pharmacovigilance Study.Targeted oncology · 2021Article
- Playing the Devil's Advocate: Should We Give a Second Chance to mTOR Inhibition in Renal Clear Cell Carcinoma? - ie Strategies to Revert Resistance to mTOR Inhibitors.Cancer management and research · 2021Review
- Phase 1 trial of vorolanib (CM082) in combination with everolimus in patients with advanced clear-cell renal cell carcinoma.EBioMedicine · 2020Article
- Y-box binding protein-1 is crucial in acquired drug resistance development in metastatic clear-cell renal cell carcinoma.Journal of experimental & clinical cancer research : CR · 2020Article
- mTOR Pathway in Gastroenteropancreatic Neuroendocrine Tumor (GEP-NETs).Frontiers in endocrinology · 2020Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundSimultaneous inhibition of the vascular epithelial growth factor (VEGF) and the mammalian target of rapamycin (mTOR) pathway may improve treatment response in advanced renal cell carcinoma (RCC). Everolimus, an oral mTOR inhibitor, and sunitinib, an oral tyrosine kinase inhibitor targeting VEGF, are standard agents in the management of metastatic RCC.
methodsSequential cohorts of 3 to 6 patients with advanced RCC received dose-escalated combinations of sunitinib (37.5 or 50 mg daily, 4 weeks on/2 weeks off) with everolimus (2.5-5 mg daily or 20-30 mg weekly). Dose-limiting toxicities (DLTs) were assessed in the first 6-week cycle to determine maximum tolerated dose (MTD). Pharmacokinetic profiles were obtained.
resultsTwenty patients (13 clear cell and 7 nonclear cell RCC) were enrolled in 5 cohorts. Daily everolimus was not tolerated when combined with sunitinib; the first 2 patients on the second cohort suffered DLTs. With weekly everolimus, the MTD was 30 mg everolimus on days 7, 14, 21, and 28, plus 37.5 mg sunitinib on days 1 to 28 of a 42-day cycle; however, chronic treatment was associated with grade 3 and 4 toxicities. A schedule of 20 mg everolimus weekly/37.5 mg sunitinib was tolerated as chronic therapy. Five patients (25%) had confirmed partial responses, and 3 had nonclear cell RCC. No unexpected accumulation of everolimus, sunitinib, or N-desethyl sunitinib was observed.
conclusionsThe combination of everolimus and sunitinib is associated with significant acute and chronic toxicities and is only tolerated at attenuated doses. Responses were observed in nonclear cell and clear cell RCC.
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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.