ArticlePediatric blood & cancer2013
A phase I trial of vorinostat and bortezomib in children with refractory or recurrent solid tumors: a Children's Oncology Group phase I consortium study (ADVL0916).
Article in Pediatric blood & cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 2 of them syntheses that pooled it.
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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
46 citing papers in PubMed, 2 syntheses or guidelines pooled it, 84 citations in OpenAlex.
- Systematic review of phase-I/II trials enrolling refractory and recurrent Ewing sarcoma: Actual knowledge and future directions to optimize the research.Cancer medicine · 2021Pooled it
- Medulloblastoma in children and adolescents: a systematic review of contemporary phase I and II clinical trials and biology update.Cancer medicine · 2017Pooled it
- A Semi-Mechanistic Population Pharmacokinetic/Pharmacodynamic Model of Bortezomib in Pediatric Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia.Clinical pharmacokinetics · 2020Trial
- Phase I/II intra-patient dose escalation study of vorinostat in children with relapsed solid tumor, lymphoma, or leukemia.Clinical epigenetics · 2019Trial
- A Phase 2 study of bortezomib combined with either idarubicin/cytarabine or cytarabine/etoposide in children with relapsed, refractory or secondary acute myeloid leukemia: a report from the Children's Oncology Group.Pediatric blood & cancer · 2014Trial
- A Phase Ib Case Series Using Bortezomib With Chemotherapy in Atypical Teratoid/Rhabdoid Tumors.Cancer medicine · 2026Article
- Combined inhibition of BETs and HDACs as a potential epigenetics-based therapy for malignant rhabdoid tumor.Cell death & disease · 2026Article
- M344 Suppresses Histone Deacetylase-Associated Phenotypes and Tumor Growth in Neuroblastoma.International journal of molecular sciences · 2025Article
- Targeting the epigenome of cancer stem cells in pediatric nervous system tumors.Molecular and cellular biochemistry · 2023Review
- Review
- Current and Emerging Therapeutic Approaches for Extracranial Malignant Rhabdoid Tumors.Cancer management and research · 2022Review
- Chemotherapy-induced peripheral neuropathy in children and adolescent cancer patients.Frontiers in molecular biosciences · 2022Review
- Relapsed Medulloblastoma in Pre-Irradiated Patients: Current Practice for Diagnostics and Treatment.Cancers · 2021Review
- Review
- Osteosarcoma in Children: Not Only Chemotherapy.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Article
- A decision process for drug discovery in retinoblastoma.Investigational new drugs · 2021Article
- Prioritization of Novel Agents for Patients with Rhabdomyosarcoma: A Report from the Children's Oncology Group (COG) New Agents for Rhabdomyosarcoma Task Force.Journal of clinical medicine · 2021Review
- Biological Role of MYCN in Medulloblastoma: Novel Therapeutic Opportunities and Challenges Ahead.Frontiers in oncology · 2021Review
- Histone Deacetylases and Histone Deacetylase Inhibitors in Neuroblastoma.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 1 country.
Funding
Abstract
backgroundA pediatric Phase I trial was performed to determine the maximum-tolerated dose, dose-limiting toxicities (DLTs), and pharmacokinetics (PK) of vorinostat and bortezomib, in patients with solid tumors. PROCEDURE: Oral vorinostat was administered on days 1-5 and 8-12 of a 21-day cycle (starting dose 180 mg/m(2) /day with dose escalations to 230 and 300 mg/m(2) /day). Bortezomib (1.3 mg/m(2) i.v.) was administered on days 1, 4, 8, and 11 of the same cycle. PK and correlative biology studies were performed during Cycle 1.
resultsTwenty-three eligible patients [17 male, median age 12 years (range: 1-20)] were enrolled of whom 17 were fully evaluable for toxicity. Cycle 1 DLTs that occurred in 2/6 patients at dose level 3 (vorinostat 300 mg/m(2) /day) were Grade 2 sensory neuropathy that progressed to Grade 4 (n = 1) and Grade 3 nausea and anorexia (n = 1). No objective responses were observed. There was wide interpatient variability in vorinostat PK parameters. Bortezomib disposition was best described by a three-compartment model that demonstrated rapid distribution followed by prolonged elimination. We did not observe a decrease in nuclear factor-κB activity or Grp78 induction after bortezomib treatment in peripheral blood mononuclear cells from solid tumor patients.
conclusionThe recommended Phase 2 dose and schedule is vorinostat (230 mg/m(2) /day PO on days 1-5 and 8-12) in combination with bortezomib (1.3 mg/m(2) /day i.v. on days 1, 4, 8, and 11 of a 21-day cycle) in children with recurrent or refractory solid tumors.
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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.