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Phase I/II intra-patient dose escalation study of vorinostat in children with relapsed solid tumor, lymphoma or

O Witt1, T Milde, H E Deubzer

  • 1Department of Pediatric Oncology, Hematology, Immunology and Pneumonology and CCU Pediatric Oncology, University Hospital of Heidelberg, Heidelberg, Germany. o.witt@dkfz.de

Klinische Padiatrie
|August 24, 2012
PubMed

Insights

Histone deacetylase (HDAC) inhibitors show promise for pediatric cancers. This trial uses an individualized dose escalation of Suberoylanilidehydroxamic acid (SAHA) in relapsed pediatric tumors, assessing toxicity and efficacy with biomarker analysis.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Histone deacetylase (HDAC) inhibitors are promising drug targets for pediatric cancers like neuroblastoma and Ewing's sarcoma.
  • Pre-clinical studies demonstrate anti-tumoral effects of HDAC inhibitors in pediatric tumor models, both as single agents and in combination therapies.
  • Suberoylanilidehydroxamic acid (SAHA, vorinostat) is a clinically advanced HDAC inhibitor, FDA-approved for refractory cutaneous T-cell lymphoma.

Purpose of the Study:

  • To evaluate the safety and efficacy of Suberoylanilidehydroxamic acid (SAHA) in pediatric patients with relapsed solid tumors, lymphoma, or leukemias.
  • To implement an individualized dose escalation strategy to optimize SAHA dosage based on patient toxicity and efficacy.
  • To conduct a comprehensive pharmacokinetic, pharmacodynamic, and biomarker analysis alongside the clinical trial.

Main Methods:

  • Phase I/II clinical trial design.
  • Individualized dose escalation of SAHA (vorinostat).
  • Pharmacokinetic, pharmacodynamic, and biomarker assessments.

Main Results:

  • Data on dose-limiting toxicities and maximum tolerated dose (MTD) will be collected.
  • Efficacy will be assessed through objective response rates and duration of response.
  • Pharmacokinetic and pharmacodynamic profiles will inform optimal dosing strategies.

Conclusions:

  • Individualized SAHA dosing may improve outcomes for pediatric patients with relapsed cancers.
  • Understanding the pharmacokinetic and pharmacodynamic properties is crucial for optimizing HDAC inhibitor therapy.
  • Biomarker analysis will help identify potential predictive markers for treatment response.

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