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

MedStar author(s):
Citation: Clinical Cancer Research. 19(16):4499-507, 2013 Aug 15.PMID: 23757352Institution: MedStar Washington Hospital CenterDepartment: Medicine/General Internal MedicineForm of publication: Journal ArticleMedline article type(s): Clinical Trial, Phase I | Journal Article | Research Support, N.I.H., Intramural | Research Support, Non-U.S. Gov'tSubject headings: *Antibiotics, Antineoplastic/tu [Therapeutic Use] | *Depsipeptides/tu [Therapeutic Use] | *Neoplasms/dt [Drug Therapy] | *Neoplasms/pa [Pathology] | Adult | Aged | Antibiotics, Antineoplastic/pd [Pharmacology] | Depsipeptides/pd [Pharmacology] | Drug Administration Schedule | Female | Humans | Male | Middle Aged | Neoplasm Staging | Neoplasms/di [Diagnosis] | Treatment OutcomeLocal holdings: Available online from MWHC library: 1995 - present (after 1 year), Available in print through MWHC library: 1999 - February 2003ISSN:
  • 1078-0432
Name of journal: Clinical cancer research : an official journal of the American Association for Cancer ResearchAbstract: CONCLUSIONS: A romidepsin dose of 7 mg/m(2) 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. 2013 AACR.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 140821s.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.RESULTS: Twenty-eight patients with solid tumors, including 11 patients with thyroid cancer were enrolled. Six dose levels were explored, and 7 mg/m(2) 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 a median 30 weeks (range, 21-112) including 6 with thyroid cancer a median of 33 weeks. PD studies detected acetylated histones in PBMCs and ECG 140821s beginning at low dose levels. Follow-up RAI scans in patients with RAI refractory thyroid cancer did not detect meaningful increases.All authors: Amiri-Kordestani L, Bates SE, Draper D, Figg WD, Fojo T, Frye R, Ghafourian K, Luchenko V, Peer CJ, Piekarz RL, Reynolds J, Skarulis M, Venzon D, Woo S, Wright JDigital Object Identifier: Date added to catalog: 2014-08-21
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Item type Current library Collection Call number Status Date due Barcode
Journal Article MedStar Authors Catalog Article Available 23757352

Available online from MWHC library: 1995 - present (after 1 year), Available in print through MWHC library: 1999 - February 2003

CONCLUSIONS: A romidepsin dose of 7 mg/m(2) 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. 2013 AACR.

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 140821s.

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.

RESULTS: Twenty-eight patients with solid tumors, including 11 patients with thyroid cancer were enrolled. Six dose levels were explored, and 7 mg/m(2) 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 a median 30 weeks (range, 21-112) including 6 with thyroid cancer a median of 33 weeks. PD studies detected acetylated histones in PBMCs and ECG 140821s beginning at low dose levels. Follow-up RAI scans in patients with RAI refractory thyroid cancer did not detect meaningful increases.

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