ArticleInvestigational new drugs2013
Phase I study of UCN-01 and perifosine in patients with relapsed and refractory acute leukemias and high-risk myelodysplastic syndrome.
Article in Investigational new drugs, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 50 citations in OpenAlex.
- Decoding the metabolic cipher of dormant cancer cells: molecular mechanisms and therapeutic potentials.Cell communication and signaling : CCS · 2026Review
- Protein Kinase C at the Crossroad of Mutations, Cancer, Targeted Therapy and Immune Response.Biology · 2023Review
- Myt1 overexpression mediates resistance to cell cycle and DNA damage checkpoint kinase inhibitors.Frontiers in cell and developmental biology · 2023Article
- AKT inhibition interferes with the expression of immune checkpoint proteins and increases NK-induced killing of HL60-AML cells.Einstein (Sao Paulo, Brazil) · 2023Article
- Rediscovery of Traditional Plant Medicine: An Underestimated Anticancer Drug of Chelerythrine.Frontiers in pharmacology · 2022Review
- Activators and Inhibitors of Protein Kinase C (PKC): Their Applications in Clinical Trials.Pharmaceutics · 2021Review
- Clinical and Molecular Differentiation Between Malignant Rhabdoid Tumor of the Kidney and Normal Tissue: A Two-Case Report.Frontiers in oncology · 2021Article
- Review of rationale and progress toward targeting cyclin-dependent kinase 2 (CDK2) for male contraception†.Biology of reproduction · 2020Review
- The PI3K-Akt-mTOR Signaling Pathway in Human Acute Myeloid Leukemia (AML) Cells.International journal of molecular sciences · 2020Review
- Dual Gene Delivery Reagents From Antiproliferative Alkylphospholipids for Combined Antitumor Therapy.Frontiers in chemistry · 2020Article
- Review of Chromatographic Bioanalytical Assays for the Quantitative Determination of Marine-Derived Drugs for Cancer Treatment.Marine drugs · 2018Review
- Article
- Maximising the potential of AKT inhibitors as anti-cancer treatments.Pharmacology & therapeutics · 2017Review
- Investigation of the Lipid Binding Properties of the Marburg Virus Matrix Protein VP40.Journal of virology · 2015Article
- [Advances in leukemia inhibitors targeting PI3K/AKT/mTOR pathway].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2015Article
- Targeting phosphatidylinositol-3-kinase pathway for the treatment of Philadelphia-negative myeloproliferative neoplasms.Molecular cancer · 2015Review
- Current clinical regulation of PI3K/PTEN/Akt/mTOR signalling in treatment of human cancer.Journal of cancer research and clinical oncology · 2015Review
- Triple Akt inhibition as a new therapeutic strategy in T-cell acute lymphoblastic leukemia.Oncotarget · 2015Article
- Outlook on PI3K/AKT/mTOR inhibition in acute leukemia.Molecular and cellular therapies · 2015Article
- Targeting the Mitotic Catastrophe Signaling Pathway in Cancer.Mediators of inflammation · 2015Review
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 4 institutions in 1 country.
Funding
Abstract
backgroundThe PI3K-Akt pathway is frequently activated in acute leukemias and represents an important therapeutic target. UCN-01 and perifosine are known to inhibit Akt activation.
methodsThe primary objective of this phase I study was to determine the maximum tolerated dose (MTD) of UCN-01 given in combination with perifosine in patients with advanced acute leukemias and myelodysplastic syndrome. Secondary objectives included safety, pharmacokinetics, pharmacodynamics, and efficacy. Perifosine 150 mg every 6 h was given orally on day 1 followed by 100 mg once a day continuously in 28-day cycles. UCN-01 was given intravenously over 3 h on day 4 at three dose levels (DL1=40 mg/m(2); DL2=65 mg/m(2); DL3=90 mg/m(2)).
resultsThirteen patients were treated (DL1, n=6; DL2, n=4; DL3, n=3) according to a traditional "3+3" design. Two patients at the DL3 experienced dose-limiting toxicity including grade 3-4 pericardial effusion, hypotension, hyperglycemia, hyperkalemia, constitutional symptoms and grade 5 pneumonitis. Other frequent toxicities were grade 1-2 nausea, diarrhea, vomiting, fatigue and hyperglycemia. The MTD was determined to be UCN-01 65 mg/m(2) with perifosine 100 mg a day. No appreciable direct Akt inhibition could be demonstrated in patients' mononuclear cells using Western blot, however, reduced phosphorylation of the downstream target ribosomal protein S6 in leukemic blasts was noted by intracellular flow cytometry. No objective responses were observed on this study.
conclusionUCN-01 and perifosine can be safely administered, but this regimen lacked clinical efficacy. This approach may have failed because of insufficient Akt inhibition in vivo.
Indexed as
Identifiers
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.