Phase I study of vorinostat in combination with isotretinoin in patients with refractory/recurrent neuroblastoma: A new approaches to Neuroblastoma Therapy (NANT) trial.

ABSTRACT:

Background

Vorinostat combined with retinoids produces additive antitumor effects in preclinical studies of neuroblastoma. Higher systemic exposures of vorinostat than achieved in pediatric phase I trials with continuous daily dosing are necessary for in vivo increased histone acetylation and cytotoxic activity. We conducted a phase I trial in children with relapsed/refractory neuroblastoma to determine the maximum tolerated dose (MTD) of vorinostat on an interrupted schedule, escalating beyond the previously identified pediatric MTD.

Methods

Isotretinoin (cis-13-retinoic acid) 80 mg/m² /dose was administered by mouth twice daily on days 1-14 in combination with escalating doses of daily vorinostat up to 430 mg/m² /dose (days 1-4; 8-11) in each 28-day c

SUBMITTER: Pinto N 

PROVIDER: S-EPMC6040651 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature