Trial reportCancer2012
Two phase 2 trials of the novel Akt inhibitor perifosine in patients with advanced renal cell carcinoma after progression on vascular endothelial growth factor-targeted therapy.
Trial report in Cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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
19 citing papers in PubMed, 49 citations in OpenAlex.
- A randomized phase 2 study of MK-2206 versus everolimus in refractory renal cell carcinoma.Annals of oncology : official journal of the European Society for Medical Oncology · 2017Trial
- The mechanism of the PI3K-AKT-mTOR signaling pathway in renal cell carcinoma: current developments and future prospects.Frontiers in oncology · 2026Review
- Low-Dose Perifosine, a Phase II Phospholipid Akt Inhibitor, Selectively Sensitizes Drug-Resistant ABCB1-Overexpressing Cancer Cells.Biomolecules & therapeutics · 2025Article
- Metabolic reprogramming in macrophage responses.Biomarker research · 2021Review
- New Insights Into Targeting Membrane Lipids for Cancer Therapy.Frontiers in cell and developmental biology · 2020Review
- Implication of integrin α2β1 in anoikis of SK-Mel-147 human melanoma cells: a non-canonical function of Akt protein kinase.Oncotarget · 2019Article
- Maximising the potential of AKT inhibitors as anti-cancer treatments.Pharmacology & therapeutics · 2017Review
- Strategies to overcome therapeutic resistance in renal cell carcinoma.Urologic oncology · 2017Review
- Resistance to Targeted Therapies in Renal Cancer: The Importance of Changing the Mechanism of Action.Targeted oncology · 2017Review
- Perifosine as a potential novel anti-telomerase therapy.Oncotarget · 2015Article
- Current clinical regulation of PI3K/PTEN/Akt/mTOR signalling in treatment of human cancer.Journal of cancer research and clinical oncology · 2015Review
- A phase I and pharmacokinetic study of oral perifosine with different loading schedules in patients with refractory neoplasms.Cancer chemotherapy and pharmacology · 2014Article
- Inhibition of the PI3K/Akt/mTOR signaling pathway in diffuse large B-cell lymphoma: current knowledge and clinical significance.Molecules (Basel, Switzerland) · 2014Review
- Resistance to the mTOR inhibitor temsirolimus alters adhesion and migration behavior of renal cell carcinoma cells through an integrin α5- and integrin β3-dependent mechanism.Neoplasia (New York, N.Y.) · 2014Article
- Selective anti-cancer agents as anti-aging drugs.Cancer biology & therapy · 2013Article
- Sorafenib/regorafenib and phosphatidyl inositol 3 kinase/thymoma viral proto-oncogene inhibition interact to kill tumor cells.Molecular pharmacology · 2013Article
- Candidate cancer-targeting agents identified by expression-profiling arrays.OncoTargets and therapy · 2013Article
- Progress of molecular targeted therapies for advanced renal cell carcinoma.BioMed research international · 2013Review
- Novel targeting of phosphatidylinositol 3-kinase and mammalian target of rapamycin in renal cell carcinoma.Cancer journal (Sudbury, Mass.)Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundThe clinical activity of allosteric inhibitors of mammalian target of rapamycin (mTOR) inhibitors in renal cell carcinoma (RCC) may be limited by upstream activation of phosphatidylinositol 3 (PI3)-kinase/Akt resulting from mTOR1 inhibition. On the basis of this rationale, 2 independent phase 2 trials (Perifosine 228 and 231) were conducted to assess the efficacy and safety of the novel Akt inhibitor perifosine in patients with advanced RCC who had failed on previous vascular endothelial growth factor (VEGF)-targeted therapy.
methodsIn the Perifosine 228 trial, 24 patients with advanced RCC received oral perifosine (100 mg daily). Perifosine 231 enrolled 2 groups that received daily oral perifosine (100 mg daily): Group A comprised 32 patients who had received no prior mTOR inhibitor, and Group B comprised 18 patients who had received 1 prior mTOR inhibitor.
resultsIn the Perifosine 228 trial, 1 patient achieved a partial response (objective response rate, 4%; 95% confidence interval, 0.7%-20%), and 11 patients (46%) had stable disease as their best response. The median progression-free survival was 14.2 weeks (95% confidence interval, 7.7-21.6 weeks). In the Perifosine 231 trial, 5 patients achieved a partial response (objective response rate, 10%; 95% confidence interval, 4.5%-22.2%) and 16 patients (32%) had stable disease as their best response. The median progression-free survival was 14 weeks (95% confidence interval, 12.9, 20.7 weeks). Overall, perifosine was well tolerated, and there were very few grade 3 and 4 events. The most common toxicities included nausea, diarrhea, musculoskeletal pain, and fatigue.
conclusionsAlthough perifosine demonstrated activity in patients with advanced RCC after failure on VEGF-targeted therapy, its activity was not superior to currently available second-line agents. Nonetheless, perifosine may be worthy of further study in RCC in combination with other currently available therapies.
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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.