ArticleInvestigational new drugs2015
A phase 1 study with dose expansion of the CDK inhibitor dinaciclib (SCH 727965) in combination with epirubicin in patients with metastatic triple negative breast cancer.
Article in Investigational new drugs, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
What it found
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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
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.
- Signaling Pathways and Natural Compounds in Triple-Negative Breast Cancer Cell Line.Molecules (Basel, Switzerland) · 2022Pooled it
- CDK12 and CDK13 in oncology: from RNA regulation to therapeutic targeting.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- New insights into the dule roles CDK12 in human cancers: Mechanisms and interventions for cancer therapy.Journal of pharmaceutical analysis · 2025Review
- The CDK12-BRCA1 signaling axis mediates dinaciclib-associated radiosensitivity through p53-mediated cellular senescence.Molecular oncology · 2025Article
- HBV-associated hepatocellular carcinomas inhibit antitumor CD8Nature communications · 2025Article
- KIF18A and CDK1 as combined therapeutic targets in cervical and endometrial carcinomas: based on bioinformatics analysis andTranslational cancer research · 2024Article
- Seize the engine: Emerging cell cycle targets in breast cancer.Clinical and translational medicine · 2024Review
- Tubule-specific cyclin-dependent kinase 12 knockdown potentiates kidney injury through transcriptional elongation defects.International journal of biological sciences · 2024Article
- Recent Advances in Drug Discovery for Triple-Negative Breast Cancer Treatment.Molecules (Basel, Switzerland) · 2023Review
- Evaluation of CDK9 Inhibition by Dinaciclib in Combination with Apoptosis Modulating izTRAIL for the Treatment of Colorectal Cancer.Biomedicines · 2023Article
- Co-targeting CDK2 and CDK4/6 overcomes resistance to aromatase and CDK4/6 inhibitors in ER+ breast cancer.NPJ precision oncology · 2022Article
- Article
- Cyclin-dependent kinase (CDK) inhibitors in solid tumors: a review of clinical trials.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- Targeting Pyruvate Kinase M2 Phosphorylation Reverses Aggressive Cancer Phenotypes.Cancer research · 2021Article
- Investigational Drug Treatments for Triple-Negative Breast Cancer.Journal of personalized medicine · 2021Review
- Targeting cell-cycle machinery in cancer.Cancer cell · 2021Review
- The Individual Effects of Cyclin-Dependent Kinase Inhibitors on Head and Neck Cancer Cells-A Systematic Analysis.Cancers · 2021Article
- Emerging Therapeutics for Patients with Triple-Negative Breast Cancer.Current oncology reports · 2021Review
- Actin-like protein 6A/MYC/CDK2 axis confers high proliferative activity in triple-negative breast cancer.Journal of experimental & clinical cancer research : CR · 2021Article
- CDK1, CCNB1, and CCNB2 are Prognostic Biomarkers and Correlated with Immune Infiltration in Hepatocellular Carcinoma.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
purposeLow molecular weight cyclin E (LMW-E) isoforms, overexpressed in a majority (~70 %) of triple-negative breast cancers (TNBC), were found in preclinical models to mediate tumorigenesis through binding and activation of CDK2. CDK1/CDK2 inhibitors, such as dinaciclib, combined with anthracyclines, were synergistic in decreasing viability of TNBC cell lines. Based on this data, a phase 1 study was conducted to determine the maximum tolerated dose of dinaciclib in combination with epirubicin in patients with metastatic TNBC.
methodsCohorts of at least 2 patients were treated with escalating doses of dinaciclib given on day 1 followed by standard dose of epirubicin given on day 2 of a 21 day cycle. No intra-patient dose escalation was allowed. An adaptive accrual design based upon toxicity during cycle 1 determined entry into therapy cohorts. The target acceptable dose limiting toxicity (DLT) to advance to the next treatment level was 30 %.
resultsBetween 9/18/2012 and 7/18/2013, 9 patients were enrolled and treated at MD Anderson Cancer Center. DLTs included febrile neutropenia (grade 3, n = 2), syncope (grade 3, n = 2) and vomiting (grade 3, n = 1). Dose escalation did not proceed past the second cohort due to toxicity. After further accrual, the first dose level was also found to be too toxic. No treatment responses were noted, median time to progression was 5.5 weeks (range 3-12 weeks). Thus, accrual was stopped rather than explore the -1 dose level.
conclusionThe combination of dinaciclib and epirubicin is associated with substantial toxicities and does not appear to be an effective treatment option for TNBC.
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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.