ArticleAnnals of clinical and translational neurology2020
Phase I clinical trial of temsirolimus and perifosine for recurrent glioblastoma.
Article in Annals of clinical and translational neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 2 of them syntheses that pooled it.
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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
28 citing papers in PubMed, 2 syntheses or guidelines pooled it, 45 citations in OpenAlex.
- Efficacy and safety of immune checkpoint inhibitors and mTOR inhibitors as targeted therapy for glioblastoma: A systematic review and meta-analysis of randomized clinical trials.Neurosurgical review · 2026Pooled it
- PI3K/AKT/mTOR Targeting in Colorectal Cancer Radiotherapy: A Systematic Review.Journal of gastrointestinal cancer · 2025Pooled it
- Review
- Metabolism and signaling crosstalk in glioblastoma progression and therapy resistance.Molecular oncology · 2025Review
- Autophagy modulators in type 2 diabetes: A new perspective.Journal of diabetes · 2024Review
- Clinical and translational advances in primary brain tumor therapy with a focus on glioblastoma-A comprehensive review of the literature.World neurosurgery: X · 2024Review
- Coordinated Targeting of S6K1/2 and AXL Disrupts Pyrimidine Biosynthesis in PTEN-Deficient Glioblastoma.Cancer research communications · 2024Article
- The combination of temozolomide and perifosine synergistically inhibit glioblastoma by impeding DNA repair and inducing apoptosis.Cell death discovery · 2024Article
- Mechanistic insights and the clinical prospects of targeted therapies for glioblastoma: a comprehensive review.Experimental hematology & oncology · 2024Review
- Regulation of cancer stem cells and immunotherapy of glioblastoma (Review).Biomedical reports · 2024Review
- Inhibitors of phosphoinositide 3-kinase (PI3K) and phosphoinositide 3-kinase-related protein kinase family (PIKK).Journal of enzyme inhibition and medicinal chemistry · 2023Review
- PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer.Molecular cancer · 2023Review
- Review
- A Sequential Targeting Strategy Interrupts AKT-Driven Subclone-Mediated Progression in Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Signaling pathways in brain tumors and therapeutic interventions.Signal transduction and targeted therapy · 2023Review
- Advances in the regulatory mechanisms of mTOR in necroptosis.Frontiers in immunology · 2023Review
- Exploring the role of Nrf2 signaling in glioblastoma multiforme.Discover oncology · 2022Review
- Glioma targeted therapy: insight into future of molecular approaches.Molecular cancer · 2022Review
- Isoforms of autophagy-related proteins: role in glioma progression and therapy resistance.Molecular and cellular biochemistry · 2022Review
- Small Molecule Inhibitors in Adult High-Grade Glioma: From the Past to the Future.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
purposeMalignant glioma (MG) is the most deadly primary brain cancer. Signaling though the PI3K/AKT/mTOR axis is activated in most MGs and therefore a potential therapeutic target. The mTOR inhibitor temsirolimus and the AKT inhibitor perifosine are each well-tolerated as single agents but with limited activity reclinical data demonstrate synergistic anti-tumor effects from combined treatment. Therefore, we initiated a phase I trial of combined therapy in recurrent MGs to determine safety and a recommended phase II dose.
methodsAdults with recurrent MG, Karnofsky Performance Status ≥ 60 were enrolled, with no limit on the number of prior therapies. Temsirolimus dose was escalated using standard 3 + 3 design from 15 mg to 170 mg administered once weekly. Perifosine was fixed as a 600 mg load on day 1 followed by 100 mg nightly (single agent MTD) until dose level 7 when the load increased to 900 mg.
resultsWe treated 35 patients with with glioblastoma (17) or other MGs (18; including nine anaplastic astrocytoma, nine anaplastic oligodendroglioma, one anaplastic oligoastrocytoma, and two low grade astrocytomas with radiographic transformation to MG). We observed five dose-limiting toxicities (DLTs): one at dose level 3 (50mg temsirolimus), then two at dose level 7 expansion (170 mg temsirolimus), and then two more at dose level 6 expansion (170 mg temsirolimus). DLTs included thrombocytopenia (n = 3), intracerebral hemorrhage (n = 1) and lung infection (n = 1).
conclusionCombining the mTOR inhibitor temsirolimus dosed at 115 mg weekly and the AKT inhibitor perifosine dosed at 100 mg daily (following 600 mg load) is tolerable in heavily pretreated adults with recurrent MGs.
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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.