Phase i trial of a new schedule of romidepsin in patients with advanced cancers

Laleh Amiri-Kordestani, Victoria Luchenko, Cody J. Peer, Kambiz Ghafourian, James Reynolds, Deb Draper, Robin Frye, Sue Woo, David Venzon, John Wright, Monica Skarulis, William D. Figg, Tito Fojo, Susan E. Bates*, Richard L. Piekarz

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


Purpose: Romidepsin is a potent histone deacetylase inhibitor (HDI) with activity in T-cell lymphoma. Given preclinical data showing greater induction of gene expression with longer exposures to HDIs, a phase I study of a day 1, 3, and 5 romidepsin schedule was evaluated. A secondary objective was to assess the effect of romidepsin on radioactive iodine (RAI) uptake in thyroid cancers. Experimental Design: Open-label, single-arm, phase I, 3 + 3 dose escalation study. Romidepsin was administered as a 4-hour infusion on days 1, 3, and 5 of a 21-day cycle. Pharmacokinetics (PK) and pharmacodynamics (PD) were assessed, including histone acetylation in peripheral blood mononuclear cells (PBMC), RAI uptake in refractory thyroid cancer, and HDI-related ECG changes. Results: Twenty-eight patients with solid tumors, including 11 patients with thyroid cancer were enrolled. Six dose levels were explored, and 7 mg/m2 on days 1, 3, and 5 was identified as tolerable. No Response Evaluation Criteria In Solid Tumors-defined objective responses were recorded although 9 patients had stable disease amedian 30 weeks (range, 21-112) including 6 with thyroid cancer a median of 33 weeks. PD studies detected acetylated histones in PBMCs and ECG changes beginning at low dose levels. Follow-up RAI scans in patients with RAI refractory thyroid cancer did not detect meaningful increases. Conclusions: A romidepsin dose of 7 mg/m2 administered on days 1, 3, and 5 was found tolerable and resulted in histone acetylation in PBMCs. Although there were no objective responses with romidepsin alone, this schedule may be useful for developing combination studies in solid tumors.

Original languageEnglish (US)
Pages (from-to)4499-4507
Number of pages9
JournalClinical Cancer Research
Issue number16
StatePublished - Aug 15 2013

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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