Evidence map›Paper›PMID 25695691›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015

Phase I Study of Vorinostat as a Radiation Sensitizer with 131I-Metaiodobenzylguanidine (131I-MIBG) for Patients with Relapsed or Refractory Neuroblastoma.

Steven G DuBois, Susan Groshen, Julie R Park, Daphne A Haas-Kogan, Xiaodong Yang, Ethan Geier, Eugene Chen, Kathy Giacomini, Brian Weiss, Susan L Cohn and 12 more

Open access · bronzeAbstract readClinical Trial, Phase IMulticenter Study
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed, 2 pooled it
4.7field-weighted citation impact, top 5% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

41 citing papers in PubMed, 2 syntheses or guidelines pooled it, 69 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Trial
  6. Arsenic Trioxide as a Radiation Sensitizer for 131I-Metaiodobenzylguanidine Therapy: Results of a Phase II Study.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2016
    Trial
  7. Review
  8. Article
  9. Review
  10. Phase I Study ofJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025
    Article
  11. Progresses and Pitfalls of Epigenetics in Solid Tumors Clinical Trials.International journal of molecular sciences · 2024
    Review
  12. Article
  13. Review
  14. Review
  15. Combination Early-Phase Trials of Anticancer Agents in Children and Adolescents.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023
    Review
  16. Article
  17. Article
  18. Drug metabolism and disposition: the biological fate of chemicals · 2022
    Article
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors at 1 institution in 1 country.

Steven G DuBoisDepartment of Pediatrics, University of California San Francisco, San Francisco, California. duboiss@peds.ucsf.edu.
Susan GroshenDepartment of Preventive Medicine, USC Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles, California.
Julie R ParkDepartment of Pediatrics, University of Washington School of Medicine, Seattle, Washington.
Daphne A Haas-KoganDepartment of Radiation Oncology, University of California San Francisco, San Francisco, California.
Xiaodong YangDepartment of Radiation Oncology, University of California San Francisco, San Francisco, California.
Ethan GeierDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California.
Eugene ChenDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California.
Kathy GiacominiDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California.
Brian WeissDepartment of Pediatrics, Cincinnati Children's Medical Center, Cincinnati, Ohio.
Susan L CohnDepartment of Pediatrics, University of Chicago School of Medicine, Chicago, Illinois.
M Meaghan GrangerDepartment of Pediatrics, Cook Children's Hospital, Fort Worth, Texas.
Gregory A YanikDepartment of Pediatrics, University of Michigan Medical School, Ann Arbor, Michigan.
Randall HawkinsDepartment of Radiology, University of California San Francisco, San Francisco, California.
Jesse CourtierDepartment of Radiology, University of California San Francisco, San Francisco, California.
Hollie JacksonDepartment of Radiology, USC Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles, California.
Fariba GoodarzianDepartment of Radiology, USC Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles, California.
Hiroyuki ShimadaDepartment of Pathology, USC Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles, California.
Scarlett CzarneckiDepartment of Pediatrics, USC Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles, California.
Denice Tsao-WeiDepartment of Preventive Medicine, USC Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles, California.
Judith G VillablancaDepartment of Pediatrics, USC Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles, California.
Araz MarachelianDepartment of Pediatrics, USC Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles, California.
Katherine K MatthayDepartment of Pediatrics, University of California San Francisco, San Francisco, California.
University of California, San Francisco · US

Funding

UCSF CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTEUL1RR024131 · NCRR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JOHNSTON, S. CLAIBORNE · 2006 to 2011
$111.2M
Vascular endothelial cell integrins in angiogenesisP01CA081403 · NCI · CHILDREN'S HOSPITAL OF LOS ANGELES · PI SEEGER, ROBERT CHARLES · 2000 to 2014
$28.5M
NCI NIH HHS P01 CA081403NCRR NIH HHS UL1 RR024131PHS HHS P01 81403
6 · The paper itself

Abstract

purpose(131)I-metaiodobenzylguanidine (MIBG) is a radiopharmaceutical with activity in neuroblastoma. Vorinostat is a histone deacetylase inhibitor that has radiosensitizing properties. The goal of this phase I study was to determine the MTDs of vorinostat and MIBG in combination. EXPERIMENTAL

designPatients ≤ 30 years with relapsed/refractory MIBG-avid neuroblastoma were eligible. Patients received oral vorinostat (dose levels 180 and 230 mg/m(2)) daily days 1 to 14. MIBG (dose levels 8, 12, 15, and 18 mCi/kg) was given on day 3 and peripheral blood stem cells on day 17. Alternating dose escalation of vorinostat and MIBG was performed using a 3+3 design.

resultsTwenty-seven patients enrolled to six dose levels, with 23 evaluable for dose escalation. No dose-limiting toxicities (DLT) were seen in the first three dose levels. At dose level 4 (15 mCi/kg MIBG/230 mg/m(2) vorinostat), 1 of 6 patients had DLT with grade 4 hypokalemia. At dose level 5 (18 mCi/kg MIBG/230 mg/m(2) vorinostat), 2 patients had dose-limiting bleeding (one grade 3 and one grade 5). At dose level 5a (18 mCi/kg MIBG/180 mg/m(2) vorinostat), 0 of 6 patients had DLT. The most common toxicities were neutropenia and thrombocytopenia. The response rate was 12% across all dose levels and 17% at dose level 5a. Histone acetylation increased from baseline in peripheral blood mononuclear cells collected on days 3 and 12 to 14.

conclusionsVorinostat at 180 mg/m(2)/dose is tolerable with 18 mCi/kg MIBG. A phase II trial comparing this regimen to single-agent MIBG is ongoing.

Indexed as

3-IodobenzylguanidineAcetylationAdolescentAdultAgedChildChild, PreschoolDrug MonitoringFemaleHistonesHumansHydroxamic AcidsIodine RadioisotopesMaleMiddle AgedNeoplasm Recurrence, Local3-IodobenzylguanidineHistonesHydroxamic AcidsIodine RadioisotopesNorepinephrine Plasma Membrane Transport ProteinsRadiation-Sensitizing AgentsSLC6A2 protein, humanVorinostat

Identifiers

PMID25695691
PMCPMC4470833
OpenAlexW2101598041

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.