ArticleTargeted oncology2017
A Phase Ib Study of the Dual PI3K/mTOR Inhibitor Dactolisib (BEZ235) Combined with Everolimus in Patients with Advanced Solid Malignancies.
Article in Targeted oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01508104 (A Dose Escalation, Single Arm, Phase 1b-2 Combination Study of BEZ235 With Everolimus to Determine the Safety, Pharmacodynamics and Pharmacokinetics in Subjects With Advanced Solid Malignancies), which is not on this map. Cited by 75 papers.
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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 Dose Escalation, Single Arm, Phase 1b-2 Combination Study of BEZ235 With Everolimus to Determine the Safety, Pharmacodynamics and Pharmacokinetics in Subjects With Advanced Solid Malignancies
Who cites it
75 citing papers in PubMed, 113 citations in OpenAlex.
- Phase II Study of BEZ235 versus Everolimus in Patients with Mammalian Target of Rapamycin Inhibitor-Naïve Advanced Pancreatic Neuroendocrine Tumors.The oncologist · 2018Trial
- Insulin receptor substrate 2 (IRS2) confers resistance to PI3K pathway inhibition in PIK3CA mutant breast cancer.The Journal of biological chemistry · 2026Article
- The impact of the PI3K/AKT/mTOR signaling pathway on trastuzumab resistance in HER2-positive gastric cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Design, synthesis, and biological evaluation of procaine-based triazole-isoxazoline hybrids as selective PI3K/mTOR inhibitors for esophageal cancer therapy:RSC medicinal chemistry · 2026Article
- All-trans retinoic acid enhances anti-proliferative effect of dual PI3K and mTOR inhibitor NVP-BEZ235 in triple negative breast cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- BEZ235-Mediated PI3K/mTOR dual inhibition improves ovarian follicle survival in a preclinical model.Reproductive biology and endocrinology : RB&E · 2025Article
- Carrier-Free Cisplatin-Dactolisib Nanoparticles for Enhanced Synergistic Antitumor Efficacy.ACS biomaterials science & engineering · 2025Article
- A Perspective of PI3K/AKT/mTOR Pathway Inhibitors to Overcome Drug-resistance in Breast Cancer Therapy.Current medicinal chemistry · 2025Review
- Dysregulated PI3K/AKT signaling in oral squamous cell carcinoma: The tumor microenvironment and epigenetic modifiers as key drivers.Oncology research · 2025Review
- Targeting myeloid cells to improve cancer immune therapy.Frontiers in immunology · 2025Review
- Targeting the PI3K Pathway: Advancements and Achievements in Breast Cancer Therapy.Current pharmaceutical design · 2025Review
- Combination Therapy Approach to Overcome the Resistance to PI3K Pathway Inhibitors in Gynecological Cancers.Cells · 2024Review
- Resistance to Targeted Inhibitors of the PI3K/AKT/mTOR Pathway in Advanced Oestrogen-Receptor-Positive Breast Cancer.Cancers · 2024Review
- Targeted Treatment against Cancer Stem Cells in Colorectal Cancer.International journal of molecular sciences · 2024Review
- PI3K/Akt/mTOR Signaling Pathway as a Target for Colorectal Cancer Treatment.International journal of molecular sciences · 2024Review
- Molecular Targeting of the Phosphoinositide-3-Protein Kinase (PI3K) Pathway across Various Cancers.International journal of molecular sciences · 2024Review
- Attenuation of PI3K-Akt-mTOR Pathway to Reduce Cancer Stemness on Chemoresistant Lung Cancer Cells by Shikonin and Synergy with BEZ235 Inhibitor.International journal of molecular sciences · 2024Article
- Targeting regulated cell death pathways in cancers for effective treatment: a comprehensive review.Frontiers in cell and developmental biology · 2024Review
- Colorectal Cancer Stem Cells and Targeted Agents.Pharmaceutics · 2023Review
- Everolimus-induced hyperpermeability of endothelial cells causes lung injury.Experimental biology and medicine (Maywood, N.J.) · 2023Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe combination of everolimus and the imidazoquinoline derivative, BEZ235 (dactolisib), a dual PI3K/mTOR inhibitor, demonstrated synergy in a preclinical model.
objectiveTo establish clinical feasibility, a phase Ib dose-escalation trial investigating safety and pharmacokinetics of this combination in patients with advanced tumors was performed. PATIENTS AND
methodsBEZ235 was orally administered daily in escalating doses of 200, 400, and 800 mg along with everolimus at 2.5 mg daily in 28-day cycles. Nineteen patients were enrolled. Adverse events and tumor responses were evaluated using CTCAE v4.0 and RECIST 1.1, respectively. Pharmacokinetic analyses were performed.
resultsCommon toxicities observed included fatigue, diarrhea, nausea, mucositis, and elevated liver enzymes. No confirmed responses were observed. BEZ235 pharmacokinetics exhibited dose-proportional increases in C
conclusionsThe combination of BEZ235 and everolimus demonstrated limited efficacy and tolerance. BEZ235 systemic exposure increased in a dose-proportional manner while oral bioavailability was quite low, which may be related to gastrointestinal-specific toxicity. The changes in steady-state pharmacokinetics of everolimus with BEZ235 highlight potential drug-drug interactions when these two drugs are administered together. Clinicaltrials.gov: NCT01508104.
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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.