ArticleOncotarget2016
Phase I dose-escalation study of the mTOR inhibitor sirolimus and the HDAC inhibitor vorinostat in patients with advanced malignancy.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Pooled it
- Emerging targets and translational challenges in treating paclitaxel-induced peripheral neuropathy.Molecular biology reports · 2025Review
- Review
- Unveiling the Role of Mechanistic Target of Rapamycin Kinase (MTOR) Signaling in Cancer Progression and the Emergence of MTOR Inhibitors as Therapeutic Strategies.ACS pharmacology & translational science · 2024Review
- Progresses and Pitfalls of Epigenetics in Solid Tumors Clinical Trials.International journal of molecular sciences · 2024Review
- Large-scale foundation model on single-cell transcriptomics.Nature methods · 2024Article
- Epigenetic Therapies and Biomarkers in Breast Cancer.Cancers · 2022Review
- Potential of histone deacetylase inhibitors in the control and regulation of prostate, breast and ovarian cancer.Frontiers in chemistry · 2022Review
- Review
- Mixed phenotype acute leukemia in a child associated with a NUP98-NSD1 fusion and NRAS p.Gly61Arg mutation.Cancer reports (Hoboken, N.J.) · 2021Article
- The Role of Epigenetics in the Progression of Clear Cell Renal Cell Carcinoma and the Basis for Future Epigenetic Treatments.Cancers · 2021Review
- In Silico Strategy for Targeting the mTOR Kinase at Rapamycin Binding Site by Small Molecules.Molecules (Basel, Switzerland) · 2021Article
- Anticancer Therapy with HDAC Inhibitors: Mechanism-Based Combination Strategies and Future Perspectives.Cancers · 2021Review
- [The clinical observation of sirolimus combined with calcineurin inhibitors for steroid-resistant/steroid-dependent extensive cGVHD].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2020Article
- Tuning mTORC1 activity dictates the response of acute myeloid leukemia to LSD1 inhibition.Haematologica · 2020Article
- Combining epigenetic drugs with other therapies for solid tumours - past lessons and future promise.Nature reviews. Clinical oncology · 2020Review
- Hepigenetics: A Review of Epigenetic Modulators and Potential Therapies in Hepatocellular Carcinoma.BioMed research international · 2020Review
- Fluvastatin potentiates anticancer activity of vorinostat in renal cancer cells.Cancer science · 2020Article
- Small Molecules Targeting HATs, HDACs, and BRDs in Cancer Therapy.Frontiers in oncology · 2020Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 4 institutions in 1 country.
Funding
Abstract
Preclinical models suggest that histone deacetylase (HDAC) and mammalian target of rapamycin (mTOR) inhibitors have synergistic anticancer activity. We designed a phase I study to determine the safety, maximum tolerated dose (MTD), recommended phase II dose (RP2D), and dose-limiting toxicities (DLTs) of combined mTOR inhibitor sirolimus (1 mg-5 mg PO daily) and HDAC inhibitor vorinostat (100 mg-400 mg PO daily) in patients with advanced cancer. Seventy patients were enrolled and 46 (66%) were evaluable for DLT assessment since they completed cycle 1 without dose modification unless they had DLT. DLTs comprised grade 4 thrombocytopenia (n = 6) and grade 3 mucositis (n = 1). Sirolimus 4 mg and vorinostat 300 mg was declared RP2D because MTD with sirolimus 5 mg caused significant thrombocytopenia. The grade 3 and 4 drug-related toxic effects (including DLTs) were thrombocytopenia (31%), neutropenia (8%), anemia (7%), fatigue (3%), mucositis (1%), diarrhea (1%), and hyperglycemia (1%). Of the 70 patients, 35 (50%) required dose interruption or modification and 61 were evaluable for response. Partial responses were observed in refractory Hodgkin lymphoma (-78%) and perivascular epithelioid tumor (-54%), and stable disease in hepatocellular carcinoma and fibromyxoid sarcoma. In conclusion, the combination of sirolimus and vorinostat was feasible, with thrombocytopenia as the main DLT. Preliminary anticancer activity was observed in patients with refractory Hodgkin lymphoma, perivascular epithelioid tumor, and hepatocellular carcinoma.
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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.