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Ref Type Journal Article
PMID (25695691)
Authors DuBois SG, Groshen S, Park JR, Haas-Kogan DA, Yang X, Geier E, Chen E, Giacomini K, Weiss B, Cohn SL, Granger MM, Yanik GA, Hawkins R, Courtier J, Jackson H, Goodarzian F, Shimada H, Czarnecki S, Tsao-Wei D, Villablanca JG, Marachelian A, Matthay KK
Title Phase I Study of Vorinostat as a Radiation Sensitizer with 131I-Metaiodobenzylguanidine (131I-MIBG) for Patients with Relapsed or Refractory Neuroblastoma.
Journal Clinical cancer research : an official journal of the American Association for Cancer Research
Vol 21
Issue 12
Date 2015 Jun 15
URL
Abstract Text (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.Patients ≤ 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.Twenty-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.Vorinostat 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.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown neuroblastoma not applicable 131I-MIBG + Vorinostat Phase I Actionable In a Phase I clinical trial, the combination of 131I-MIBG with Zolinza (vorinostat) as a radiosensitizer demonstrated preliminary efficacy at the recommended Phase II dose, with in an overall objective response rate of 17% (1/6) and MIBG response rate of 67% (4/6) in patients with neuroblastoma (PMID: 25695691). 25695691