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Laboratory correlates for a phase II trial of romidepsin in cutaneous and peripheral T-cell lymphoma

  1. Author:
    Bates, S. E.
    Zhan, Z. R.
    Steadman, K.
    Obrzut, T.
    Luchenko, V.
    Frye, R.
    Robey, R. W.
    Turner, M.
    Gardner, E. R.
    Figg, W. D.
    Steinberg, S. M.
    Ling, A.
    Fojo, T.
    To, K. W.
    Piekarz, R. L.

  2. Author Address

    [Bates, Susan E.; Zhan, Zhirong; Steadman, Kenneth; Obrzut, Tomasz; Luchenko, Victoria; Frye, Robin; Robey, Robert W.; Fojo, Tito; To, Kin Wah; Piekarz, Richard L.] NIH, Med Oncol Branch, Bethesda, MD 20892 USA. [Turner, Maria] NIH, Dermatol Branch, Bethesda, MD 20892 USA. [Gardner, Erin R.] NCI Frederick, SAIC Frederick, Clin Pharmacol Program, Frederick, MD USA. [Figg, William D.] NIH, Clin Pharmacol Program, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NIH, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. [Ling, Alex] NIH, Dept Radiol, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA.;Bates, SE, NIH, Med Oncol Branch, 9000 Rockville Pike,Bldg 10,Rm 12N226, Bethesda, MD 20892 USA.;sebates@helix.nih.gov
    1. Year: 2010
    2. Date: Jan
  2. Journal: British Journal of Haematology
    1. 148
    2. 2
    3. Pages: 256-267
  4. Type of Article: Article
  5. ISSN: 0007-1048
  1. Abstract:

    P>Romidepsin has shown promise in the treatment of T-cell lymphomas, and so we evaluated molecular endpoints gathered from 61 patients enrolled on a phase II trial of romidepsin in cutaneous and peripheral T-cell lymphoma at the National Institutes of Health. The endpoints included histone H3 acetylation and ABCB1 gene expression in peripheral blood mononuclear cells (PBMCs); ABCB1 gene expression in tumour biopsy samples; and blood fetal haemoglobin levels (HbF), all of which were increased following romidepsin treatment. The fold increase in histone acetylation in PBMCs at 24 h was weakly to moderately well correlated with the pharmacokinetic parameters C-max and area under the curve (AUC)(last) (rho = 0 center dot 37, P = 0 center dot 03 and rho = 0 center dot 36, P = 0 center dot 03 respectively) and inversely associated with clearance (rho = -0 center dot 44; P = 0 center dot 03). Histone acetylation in PBMCs at 24 h was associated with response (P = 0 center dot 026) as was the increase in fetal haemoglobin (P = 0 center dot 014); this latter association may be due to the longer on-study duration for patients with disease response. Together, these results suggest that pharmacokinetics may be an important determinant of response to histone deacetylase inhibitors (HDIs) - the association with histone acetylation in PBMCs at 24 h is consistent with a hypothesis that potent HDIs are needed for a critical threshold of drug exposure and durable activity.

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  2. DOI: 10.1111/j.1365-2141.2009.07954.x
  3. View record in Web of Science®
  4. WOS: 000272884100008

Library Notes

  1. Fiscal Year: FY2009-2010
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