Trial reportCancer2015
Everolimus combined with gefitinib in patients with metastatic castration-resistant prostate cancer: Phase 1/2 results and signaling pathway implications.
Trial report in Cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- mTOR Inhibitors in Castration-Resistant Prostate Cancer: A Systematic Review.Targeted oncology · 2017Pooled it
- A phase II study of the dual mTOR inhibitor MLN0128 in patients with metastatic castration resistant prostate cancer.Investigational new drugs · 2018Trial
- Phase II trial of the PI3 kinase inhibitor buparlisib (BKM-120) with or without enzalutamide in men with metastatic castration resistant prostate cancer.European journal of cancer (Oxford, England : 1990) · 2017Trial
- Review
- Uncoupling of Akt and mTOR signaling drives resistance to Akt inhibition in PTEN loss prostate cancers.Science advances · 2025Article
- Amiloride Sensitizes Prostate Cancer Cells to the Reversible Tyrosine Kinase Inhibitor Lapatinib by Modulating ERBB3 Subcellular Localization.Research square · 2024Article
- The role of autophagy in prostate cancer and prostatic diseases: a new therapeutic strategy.Prostate cancer and prostatic diseases · 2024Review
- Mechanistic insights and the clinical prospects of targeted therapies for glioblastoma: a comprehensive review.Experimental hematology & oncology · 2024Review
- Exploring the mTOR Signalling Pathway and Its Inhibitory Scope in Cancer.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Transcriptomic Signature and Growth Factor Regulation of Castration-Tolerant Prostate Luminal Progenitor Cells.Cancers · 2022Article
- Defining the therapeutic selective dependencies for distinct subtypes of PI3K pathway-altered prostate cancers.Nature communications · 2021Article
- Inhibitors of the PI3K/Akt/mTOR Pathway in Prostate Cancer Chemoprevention and Intervention.Pharmaceutics · 2021Review
- Prostate Cancer Immunotherapy-Finally in From the Cold?Current oncology reports · 2021Review
- A phase I trial of temsirolimus and erlotinib in patients with refractory solid tumors.Cancer chemotherapy and pharmacology · 2021Article
- Review
- Multiplex Immunofluorescence in Formalin-Fixed Paraffin-Embedded Tumor Tissue to Identify Single-Cell-Level PI3K Pathway Activation.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- Review
- Pleiotropic Impact of DNA-PK in Cancer and Implications for Therapeutic Strategies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Aberrant Expression of ERG Promotes Resistance to Combined PI3K and AR Pathway Inhibition through Maintenance of AR Target Genes.Molecular cancer therapeutics · 2019Article
- Targeting mTOR for cancer therapy.Journal of hematology & oncology · 2019Review
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 3 institutions in 2 countries.
Funding
Abstract
backgroundThe effects of mammalian target of rapamycin (mTOR) inhibition are limited by feedback reactivation of receptor tyrosine kinase signaling in phosphatase and tensin homolog-null tumors. Thus, this study tested the combination of mTOR inhibition (everolimus) and epidermal growth factor receptor inhibition (gefitinib) in castration-resistant prostate cancer (CRPC).
methodsIn phase 1, 12 patients (10 with CRPC and 2 with glioblastoma) received daily gefitinib (250 mg) with weekly everolimus (30, 50, or 70 mg). In phase 2, 27 CRPC patients received gefitinib with everolimus (70 mg).
resultsPhase 1 revealed no pharmacokinetic interactions and no dose-limiting toxicities. In phase 2, 18 of 27 patients (67%) discontinued treatment before the 12-week evaluation because of progression as evidenced by prostate-specific antigen (PSA) levels (n = 6) or imaging (n = 5) or because of a grade 2 or higher toxicity (n = 7). Thirteen of the 37 CRPC patients (35%) exhibited a rapidly rising PSA level after they had begun treatment, and this declined upon discontinuation. Fluorodeoxyglucose positron emission tomography 24 to 72 hours after the initiation of treatment showed a decrease in the standardized uptake value consistent with mTOR inhibition in 27 of the 33 evaluable patients (82%); there was a corresponding rise in PSA in 20 of these 27 patients (74%).
conclusionsThe combination of gefitinib and everolimus did not result in significant antitumor activity. The induction of PSA in tumors treated with mTOR inhibitors was consistent with preclinical data showing that phosphoinositide 3-kinase (PI3K) pathway signaling feedback inhibits the androgen receptor (AR). This clinical evidence of relief of feedback inhibition promoting enhanced AR activity supports future studies combining PI3K pathway inhibitors and second-generation AR inhibitors in CRPC.
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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.