ArticleCancer chemotherapy and pharmacology2010
A phase I trial of UCN-01 and prednisone in patients with refractory solid tumors and lymphomas.
Article in Cancer chemotherapy and pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 34 citations in OpenAlex.
- A phase II study of cell cycle inhibitor UCN-01 in patients with metastatic melanoma: a California Cancer Consortium trial.Investigational new drugs · 2012Trial
- Protein Kinase C Family: Structures, Biological Functions, Diseases, and Pharmaceutical Interventions.MedComm · 2025Review
- 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
- Activators and Inhibitors of Protein Kinase C (PKC): Their Applications in Clinical Trials.Pharmaceutics · 2021Review
- Targeting Dormant Ovarian Cancer CellsMolecular cancer therapeutics · 2021Article
- Novel clinical indenoisoquinoline topoisomerase I inhibitors: a twist around the camptothecins.Oncotarget · 2018Article
- Review of Chromatographic Bioanalytical Assays for the Quantitative Determination of Marine-Derived Drugs for Cancer Treatment.Marine drugs · 2018Review
- UCN-01 enhances cytotoxicity of irinotecan in colorectal cancer stem-like cells by impairing DNA damage response.Oncotarget · 2016Article
- Structure-based design, discovery and development of checkpoint kinase inhibitors as potential anticancer therapies.Expert opinion on drug discovery · 2013Review
- UCN-01 induces S and G2/M cell cycle arrest through the p53/p21(waf1) or CHK2/CDC25C pathways and can suppress invasion in human hepatoma cell lines.BMC cancer · 2013Article
- Phase I dose-escalation study to examine the safety and tolerability of LY2603618, a checkpoint 1 kinase inhibitor, administered 1 day after pemetrexed 500 mg/m(2) every 21 days in patients with cancer.Investigational new drugs · 2013Article
- Mitosis-targeted anti-cancer therapies: where they stand.Cell death & disease · 2012Review
- Role of checkpoint kinase 1 (Chk1) in the mechanisms of resistance to histone deacetylase inhibitors.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- A small-molecule screening strategy to identify suppressors of statin myopathy.ACS chemical biology · 2011Article
- Identification of a conserved anti-apoptotic protein that modulates the mitochondrial apoptosis pathway.PloS one · 2011Article
- Trial Watch: Targeting ATM-CHK2 and ATR-CHK1 pathways for anticancer therapy.Molecular & cellular oncologyReview
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
purposeUCN-01 potently inhibits protein kinase C, phosphatidylinositide-dependent kinase-1, and checkpoint kinase 1, which are involved in regulating cell cycle progression. We designed a phase I study to determine the maximum tolerated dose (MTD) of UCN-01 with prednisone in patients with advanced malignancies.
methodsUCN-01 was administered as a continuous intravenous infusion over 72 h in cycle 1 and 36 h in subsequent cycles. Prednisone was given orally at 60 mg/m(2) per day for five consecutive days within each 28-day cycle. Standard dose escalation was employed, and MTD was defined as the dose at which no more than one of six patients experienced a dose-limiting toxicity (DLT). Plasma pharmacokinetics of UCN-01 were assessed.
resultsFifteen patients received a total of 55 courses of treatment. The MTD and the recommended phase II dose of UCN-01 in this combination is 72 mg/m(2) total dose over 72 h for cycle 1 followed by 36 mg/m(2) per cycle over 36 h. All patients experienced hyperglycemia but responded to insulin treatment. Hypophosphatemia was a DLT in two patients. There were no cumulative toxicities. No objective responses were observed, but five patients had stable disease, including two patients with lymphoid malignancies who had prolonged disease stabilizations. UCN-01 has a long terminal half-life and low clearance; there was wide inter-patient variability in peak concentrations.
conclusionUCN-01 can be safely administered in combination with prednisone without unacceptable toxicity. The prolonged stable disease in two patients with lymphoid malignancies is a proof of principle for the evaluation of cyclin-dependent kinase inhibitors in oncology.
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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.