ArticleInvestigational new drugs2013
A phase I study of sorafenib and vorinostat in patients with advanced solid tumors with expanded cohorts in renal cell carcinoma and non-small cell lung cancer.
Article in Investigational new drugs, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Inefficiencies and Patient Burdens in the Development of the Targeted Cancer Drug Sorafenib: A Systematic Review.PLoS biology · 2017Pooled it
- Histone deacetylases and their inhibitors in kidney diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- DNA and histone modifications as potent diagnostic and therapeutic targets to advance non-small cell lung cancer management from the perspective of 3P medicine.The EPMA journal · 2022Review
- Histone Modification in NSCLC: Molecular Mechanisms and Therapeutic Targets.International journal of molecular sciences · 2021Review
- The Role of Epigenetics in the Progression of Clear Cell Renal Cell Carcinoma and the Basis for Future Epigenetic Treatments.Cancers · 2021Review
- Epigenetic Alterations in Renal Cell Cancer With TKIs Resistance: From Mechanisms to Clinical Applications.Frontiers in genetics · 2020Review
- Antitumor Activity of a Novel Tyrosine Kinase Inhibitor AIU2001 Due to Abrogation of the DNA Damage Repair in Non-Small Cell Lung Cancer Cells.International journal of molecular sciences · 2019Article
- Combating pancreatic cancer with PI3K pathway inhibitors in the era of personalised medicine.Gut · 2019Review
- Epigenetics in renal cell cancer: mechanisms and clinical applications.Nature reviews. Urology · 2018Review
- Suppression of Adaptive Responses to Targeted Cancer Therapy by Transcriptional Repression.Cancer discovery · 2018Article
- Epigenetic Regulators in the Development, Maintenance, and Therapeutic Targeting of Acute Myeloid Leukemia.Frontiers in oncology · 2018Review
- Designs for phase I trials in ordered groups.Statistics in medicine · 2017Article
- Selective Inhibitors of Histone Deacetylases 1 and 2 Synergize with Azacitidine in Acute Myeloid Leukemia.PloS one · 2017Article
- Epigenetic therapy approaches in non-small cell lung cancer: Update and perspectives.Epigenetics · 2016Review
- Synergistic activity of vorinostat combined with gefitinib but not with sorafenib in mutant KRAS human non-small cell lung cancers and hepatocarcinoma.OncoTargets and therapy · 2016Article
- Review
- Suberoylanilide hydroxamic acid treatment reveals crosstalks among proteome, ubiquitylome and acetylome in non-small cell lung cancer A549 cell line.Scientific reports · 2015Article
- Epigenetic treatment of solid tumours: a review of clinical trials.Clinical epigenetics · 2015Review
- Targeted polytherapy in small cell sarcoma and its association with doxorubicin.Molecular oncology · 2014Article
- A combination of p300 and Braf expression in the diagnosis and prognosis of melanoma.BMC cancer · 2014Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThis phase I study evaluated the safety, tolerability and preliminary efficacy of sorafenib combined with vorinostat in patients with solid tumors. PATIENTS AND
methodsPatients were treated with sorafenib 400 mg po bid daily and vorinostat 200-400 mg po days 1-14 of a 21 day cycle to establish the recommended phase II dose (RP2D). The tolerability and efficacy of the RP2D was further tested in two cohorts of 6-12 patients each with advanced RCC and NSCLC.
results17 patients were treated in the dose escalation phase that established the RP2D at sorafenib 400 mg po bid daily, vorinostat 300 mg po days 1-14. Dose limiting toxicities (DLT) included intolerable grade 2 hand-foot syndrome and multiple grade 1 toxicities causing dose interruption for more than 14 days. Despite good tolerance in the all-comers population, the RP2D was poorly tolerated in the RCC and NSCLC cohorts with the majority being unable to finish 2 full cycles of therapy. Although there were no confirmed responses, 1 patient each with NSCLC adenocarcinoma and renal sarcoma had unconfirmed partial responses and 5 of 8 patients with RCC having durable minor responses (11-26 %), including 2 who were on treatment for nearly a year.
conclusionsAlthough tolerable in other tumor types, sorafenib 400 mg po bid with vorinostat 300 mg po daily days 1-14 of a 21-day cycle is not tolerable without dose reductions/delays in RCC and NSCLC patients. These patients may require lower doses than the RP2D explored within this study. No confirmed responses were seen but minor responses particularly in RCC were observed.
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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.