ArticleCancer chemotherapy and pharmacology2011
A Phase 1 study of UCN-01 in combination with irinotecan in patients with resistant solid tumor malignancies.
Article in Cancer chemotherapy and pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 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.
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Who cites it
34 citing papers in PubMed, 68 citations in OpenAlex.
- A phase II study of UCN-01 in combination with irinotecan in patients with metastatic triple negative breast cancer.Breast cancer research and treatment · 2013Trial
- CHK1 targets spleen tyrosine kinase (L) for proteolysis in hepatocellular carcinoma.The Journal of clinical investigation · 2012Trial
- A phase II study of cell cycle inhibitor UCN-01 in patients with metastatic melanoma: a California Cancer Consortium trial.Investigational new drugs · 2012Trial
- Decoding the metabolic cipher of dormant cancer cells: molecular mechanisms and therapeutic potentials.Cell communication and signaling : CCS · 2026Review
- Profile of Helen M. Piwnica-Worms.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Ferrocene thiazolidine-2,4-dione derivatives cause DNA damage and interfere with DNA repair in triple-negative breast cancer cells.PloS one · 2025Article
- DNA damage response in breast cancer and its significant role in guiding novel precise therapies.Biomarker research · 2024Review
- The treatment landscape of triple-negative breast cancer.Medical oncology (Northwood, London, England) · 2024Review
- Triple-Negative Breast Cancer and Emerging Therapeutic Strategies: ATR and CHK1/2 as Promising Targets.Cancers · 2024Review
- Protein Kinase C at the Crossroad of Mutations, Cancer, Targeted Therapy and Immune Response.Biology · 2023Review
- Rational Drug Design of Targeted and Enzyme-Cleavable Vitamin E Analogs as a Neoadjuvant to Chemotherapy:ACS pharmacology & translational science · 2023Article
- 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
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- Targeting Dormant Ovarian Cancer CellsMolecular cancer therapeutics · 2021Article
- Therapeutic landscape in mutational triple negative breast cancer.Molecular cancer · 2018Review
- A Functional Signature Ontology (FUSION) screen detects an AMPK inhibitor with selective toxicity toward human colon tumor cells.Scientific reports · 2018Article
- Molecularly targeted therapies for p53-mutant cancers.Cellular and molecular life sciences : CMLS · 2017Review
- UCN-01 enhances cytotoxicity of irinotecan in colorectal cancer stem-like cells by impairing DNA damage response.Oncotarget · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors at 6 institutions in 2 countries.
Funding
Abstract
purposeUCN-01 (7-hydroxystaurosporine) is a multi-targeted protein kinase inhibitor that exhibits synergistic activity with DNA-damaging agents in preclinical studies. We conducted a Phase I study to determine the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetic, and pharmacodynamic effects of UCN-01 and irinotecan in patients with resistant solid tumors. EXPERIMENTAL
designPatients received irinotecan (75-125 mg/m(2) IV on days 1, 8, 15, 22) and UCN-01 (50-90 mg/m(2) IV on day 2 and 25-45 mg/m(2) on day 23 and subsequent doses) every 42 days. Blood for pharmacokinetics of UCN-01 and irinotecan, and blood, normal rectal mucosa, and tumor biopsies for pharmacodynamic studies were obtained.
resultsTwenty-five patients enrolled to 5 dose levels. The MTD was irinotecan 125 mg/m(2) on days 1, 8, 15, 22 and UCN-01 70 mg/m(2) on day 2 and 35 mg/m(2) on day 23. DLTs included grade 3 diarrhea/dehydration and dyspnea. UCN-01 had a prolonged half-life and a low clearance rate. There was a significant reduction in SN-38 C(max) and aminopentanocarboxylic acid (APC) and SN-38 glucuronide half-lives. Phosphorylated ribosomal protein S6 was reduced in blood, normal rectal mucosa, and tumor biopsies at 24 h post-UCN-01. Two partial responses were observed in women with ER, PgR, and HER2-negative breast cancers (TBNC). Both tumors were defective for p53. Twelve patients had stable disease (mean duration 18 weeks, range 7-30 weeks).
conclusionUCN-01 and irinotecan demonstrated acceptable toxicity and target inhibition. Anti-tumor activity was observed and a study of this combination in women with TNBC is underway.
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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.