Phase 1 Study of Vorinostat as a Radiation Sensitizer with 131I-Metaiodobenzylguanidine (131I-MIBG) for Patients with Relapsed or Refractory Neuroblastoma
| Autor: | DuBois, Steven G., Groshen, Susan, Park, Julie R., Haas-Kogan, Daphne A., Yang, Xiaodong, Geier, Ethan, Chen, Eugene, Giacomini, Kathy, Weiss, Brian, Cohn, Susan L., Granger, M. Meaghan, Yanik, Gregory A., Hawkins, Randall, Courtier, Jesse, Jackson, Hollie, Goodarzian, Fariba, Shimada, Hiroyuki, Czarnecki, Scarlett, Tsao-Wei, Denice, Villablanca, Judith G., Marachelian, Araz, Matthay, Katherine K. |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Radiation-Sensitizing Agents Vorinostat Norepinephrine Plasma Membrane Transport Proteins Adolescent Acetylation Middle Aged Hydroxamic Acids Article Histones Iodine Radioisotopes 3-Iodobenzylguanidine Neuroblastoma Young Adult Treatment Outcome Child Preschool Humans Female Drug Monitoring Neoplasm Recurrence Local Child Aged |
| Popis: | (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. |
| Databáze: | OpenAIRE |
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