ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
Phase I study of oral rigosertib (ON 01910.Na), a dual inhibitor of the PI3K and Plk1 pathways, in adult patients with advanced solid malignancies.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03745911 (Phase II Study of Paclitaxel and TAK-228 in Metastatic Urothelial Carcinoma), which is not on this map. Cited by 41 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.
Phase II Study of Paclitaxel and TAK-228 in Metastatic Urothelial Carcinoma (UC) and the Impact of PI3K-mTOR Pathway Genomic Alterations
Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Effectiveness, safety and pharmacokinetics of Polo-like kinase 1 inhibitors in tumor therapy: A systematic review and meta-analysis.Frontiers in oncology · 2023Pooled it
- Discovery of a novel PLK1 inhibitor with high inhibitory potency using a combined virtual screening strategy.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Dissecting endometrial cancer complexity in response to standard and targeted therapies.Cell death & disease · 2025Article
- Review
- Unlocking the therapeutic potential of rigosertib as a selective therapy for ovarian cancer.Cell reports. Medicine · 2025Article
- PLK1 inhibitors for the treatment of colorectal cancer.Annals of medicine and surgery (2012) · 2025Review
- Onvansertib and Navitoclax Combination as a New Therapeutic Option for Mucinous Ovarian Carcinoma.International journal of molecular sciences · 2025Article
- Clinical relevance of PLK1 in epithelial ovarian cancer.Frontiers in pharmacology · 2025Review
- PLK1 inhibitors as a new targeted treatment for adrenocortical carcinoma.Endocrine connections · 2024Article
- Recent Advances in Drug Discovery for Triple-Negative Breast Cancer Treatment.Molecules (Basel, Switzerland) · 2023Review
- New insights into RAS in head and neck cancer.Biochimica et biophysica acta. Reviews on cancer · 2023Review
- Another Brick to Confirm the Efficacy of Rigosertib as Anticancer Agent.International journal of molecular sciences · 2023Article
- Multiomics characterization implicates PTK7 in ovarian cancer EMT and cell plasticity and offers strategies for therapeutic intervention.Cell death & disease · 2022Article
- Genome maintenance in retinoblastoma: Implications for therapeutic vulnerabilities.Oncology letters · 2022Review
- Present and Future Perspective on PLK1 Inhibition in Cancer Treatment.Frontiers in oncology · 2022Review
- Inhibition of the PLK1-Coupled Cell Cycle Machinery Overcomes Resistance to Oxaliplatin in Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Therapeutic Targeting PLK1 by ON-01910.Na Is Effective in Local Treatment of Retinoblastoma.Oncology research · 2021Article
- Rigosertib inhibits MEK1-ERK pathway and alleviates lipopolysaccharide-induced sepsis.Immunity, inflammation and disease · 2021Article
- Anti-tumor effects of rigosertib in high-risk neuroblastoma.Translational oncology · 2021Article
- In Vitro Evaluation of Rigosertib Antitumoral and Radiosensitizing Effects against Human Cholangiocarcinoma Cells.International journal of molecular sciences · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 1 institution in 1 country.
Funding
Abstract
purposeTo determine the pharmacokinetics (PK), maximum tolerated dose (MTD), safety, and antitumor activity of an oral formulation of rigosertib, a dual phosphoinositide 3-kinase (PI3K) and polo-like kinase 1 (Plk1) pathway inhibitor, in patients with advanced solid malignancies. EXPERIMENTAL
designPatients with advanced solid malignancies received rigosertib twice daily continuously in 21-day cycles. Doses were escalated until intolerable grade ≥2 toxicities, at which point the previous dose level was expanded to define the MTD. All patients were assessed for safety, PK, and response. Urinary PK were performed at the MTD. Archival tumors were assessed for potential molecular biomarkers with multiplex mutation testing. A subset of squamous cell carcinomas (SCC) underwent exome sequencing.
resultsForty-eight patients received a median of 2 cycles of therapy at 5 dose levels. Rigosertib exposure increased with escalating doses. Dose-limiting toxicities were hematuria and dysuria. The most common grade ≥2 drug-related toxicities involved urothelial irritation. The MTD is 560 mg twice daily. Activity was seen in head and neck SCCs (1 complete response, 1 partial response) and stable disease for ≥12 weeks was observed in 8 additional patients. Tumors experiencing ≥partial response had PI3K pathway activation, inactivated p53, and unique variants in ROBO3 and FAT1, two genes interacting with the Wnt/β-catenin pathway.
conclusionsThe recommended phase II dose of oral rigosertib is 560 mg twice daily given continuously. Urinary toxicity is the dose-limiting and most common toxicity. Alterations in PI3K, p53, and Wnt/β-catenin pathway signaling should be investigated as potential biomarkers of response in future trials.
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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.