The optimal use of bexarotene in cutaneous T-cell lymphoma

Authors

  • R. Gniadecki,

    1. Department of Dermatology, University of Copenhagen, Bispebjerg Hospital, Bispebjerg bakke 23, DK-2400 Copenhagen, Denmark
      *Department of Dermatology and Allergy, Skin Cancer Center Charité, Charité-Universitätsmedizin Berlin, Schumannstrasse 20/21, 10117 Berlin, Germany
      †Department of Dermatology, AP-HP, Hôpital Henri Mondor, INSERM, U 659, University Paris 12, F-94010 Créteil, France
      ‡Department of Dermatology, University Hospital of Zurich, Gloriastrasse 31, CH-8091 Zurich, Switzerland
      §Department of Dermatology, University of Texas M.D. Anderson Cancer Center, Box 434, 1515 Holcombe Boulevard, Houston, TX 77030, U.S.A.
      ¶Department of Dermatology, Division of Special and Environmental Dermatology, Medical University of Vienna, Währingergürtel 18–20, A-1090 Vienna, Austria
      **Skin and Allergy Hospital, Helsinki University Hospital, PO Box 160, 00029 HUS Helsinki, Finland
      ††Arteriosklerose-Präventions-Institut München, Wilbrechtstrasse 95, D-81477 Munich, Germany
      ‡‡St John’s Institute of Dermatology, Guy’s and St Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, U.K.
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  • C. Assaf,

    1. Department of Dermatology, University of Copenhagen, Bispebjerg Hospital, Bispebjerg bakke 23, DK-2400 Copenhagen, Denmark
      *Department of Dermatology and Allergy, Skin Cancer Center Charité, Charité-Universitätsmedizin Berlin, Schumannstrasse 20/21, 10117 Berlin, Germany
      †Department of Dermatology, AP-HP, Hôpital Henri Mondor, INSERM, U 659, University Paris 12, F-94010 Créteil, France
      ‡Department of Dermatology, University Hospital of Zurich, Gloriastrasse 31, CH-8091 Zurich, Switzerland
      §Department of Dermatology, University of Texas M.D. Anderson Cancer Center, Box 434, 1515 Holcombe Boulevard, Houston, TX 77030, U.S.A.
      ¶Department of Dermatology, Division of Special and Environmental Dermatology, Medical University of Vienna, Währingergürtel 18–20, A-1090 Vienna, Austria
      **Skin and Allergy Hospital, Helsinki University Hospital, PO Box 160, 00029 HUS Helsinki, Finland
      ††Arteriosklerose-Präventions-Institut München, Wilbrechtstrasse 95, D-81477 Munich, Germany
      ‡‡St John’s Institute of Dermatology, Guy’s and St Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, U.K.
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  • M. Bagot,

    1. Department of Dermatology, University of Copenhagen, Bispebjerg Hospital, Bispebjerg bakke 23, DK-2400 Copenhagen, Denmark
      *Department of Dermatology and Allergy, Skin Cancer Center Charité, Charité-Universitätsmedizin Berlin, Schumannstrasse 20/21, 10117 Berlin, Germany
      †Department of Dermatology, AP-HP, Hôpital Henri Mondor, INSERM, U 659, University Paris 12, F-94010 Créteil, France
      ‡Department of Dermatology, University Hospital of Zurich, Gloriastrasse 31, CH-8091 Zurich, Switzerland
      §Department of Dermatology, University of Texas M.D. Anderson Cancer Center, Box 434, 1515 Holcombe Boulevard, Houston, TX 77030, U.S.A.
      ¶Department of Dermatology, Division of Special and Environmental Dermatology, Medical University of Vienna, Währingergürtel 18–20, A-1090 Vienna, Austria
      **Skin and Allergy Hospital, Helsinki University Hospital, PO Box 160, 00029 HUS Helsinki, Finland
      ††Arteriosklerose-Präventions-Institut München, Wilbrechtstrasse 95, D-81477 Munich, Germany
      ‡‡St John’s Institute of Dermatology, Guy’s and St Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, U.K.
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  • R. Dummer,

    1. Department of Dermatology, University of Copenhagen, Bispebjerg Hospital, Bispebjerg bakke 23, DK-2400 Copenhagen, Denmark
      *Department of Dermatology and Allergy, Skin Cancer Center Charité, Charité-Universitätsmedizin Berlin, Schumannstrasse 20/21, 10117 Berlin, Germany
      †Department of Dermatology, AP-HP, Hôpital Henri Mondor, INSERM, U 659, University Paris 12, F-94010 Créteil, France
      ‡Department of Dermatology, University Hospital of Zurich, Gloriastrasse 31, CH-8091 Zurich, Switzerland
      §Department of Dermatology, University of Texas M.D. Anderson Cancer Center, Box 434, 1515 Holcombe Boulevard, Houston, TX 77030, U.S.A.
      ¶Department of Dermatology, Division of Special and Environmental Dermatology, Medical University of Vienna, Währingergürtel 18–20, A-1090 Vienna, Austria
      **Skin and Allergy Hospital, Helsinki University Hospital, PO Box 160, 00029 HUS Helsinki, Finland
      ††Arteriosklerose-Präventions-Institut München, Wilbrechtstrasse 95, D-81477 Munich, Germany
      ‡‡St John’s Institute of Dermatology, Guy’s and St Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, U.K.
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  • M. Duvic,

    1. Department of Dermatology, University of Copenhagen, Bispebjerg Hospital, Bispebjerg bakke 23, DK-2400 Copenhagen, Denmark
      *Department of Dermatology and Allergy, Skin Cancer Center Charité, Charité-Universitätsmedizin Berlin, Schumannstrasse 20/21, 10117 Berlin, Germany
      †Department of Dermatology, AP-HP, Hôpital Henri Mondor, INSERM, U 659, University Paris 12, F-94010 Créteil, France
      ‡Department of Dermatology, University Hospital of Zurich, Gloriastrasse 31, CH-8091 Zurich, Switzerland
      §Department of Dermatology, University of Texas M.D. Anderson Cancer Center, Box 434, 1515 Holcombe Boulevard, Houston, TX 77030, U.S.A.
      ¶Department of Dermatology, Division of Special and Environmental Dermatology, Medical University of Vienna, Währingergürtel 18–20, A-1090 Vienna, Austria
      **Skin and Allergy Hospital, Helsinki University Hospital, PO Box 160, 00029 HUS Helsinki, Finland
      ††Arteriosklerose-Präventions-Institut München, Wilbrechtstrasse 95, D-81477 Munich, Germany
      ‡‡St John’s Institute of Dermatology, Guy’s and St Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, U.K.
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  • R. Knobler,

    1. Department of Dermatology, University of Copenhagen, Bispebjerg Hospital, Bispebjerg bakke 23, DK-2400 Copenhagen, Denmark
      *Department of Dermatology and Allergy, Skin Cancer Center Charité, Charité-Universitätsmedizin Berlin, Schumannstrasse 20/21, 10117 Berlin, Germany
      †Department of Dermatology, AP-HP, Hôpital Henri Mondor, INSERM, U 659, University Paris 12, F-94010 Créteil, France
      ‡Department of Dermatology, University Hospital of Zurich, Gloriastrasse 31, CH-8091 Zurich, Switzerland
      §Department of Dermatology, University of Texas M.D. Anderson Cancer Center, Box 434, 1515 Holcombe Boulevard, Houston, TX 77030, U.S.A.
      ¶Department of Dermatology, Division of Special and Environmental Dermatology, Medical University of Vienna, Währingergürtel 18–20, A-1090 Vienna, Austria
      **Skin and Allergy Hospital, Helsinki University Hospital, PO Box 160, 00029 HUS Helsinki, Finland
      ††Arteriosklerose-Präventions-Institut München, Wilbrechtstrasse 95, D-81477 Munich, Germany
      ‡‡St John’s Institute of Dermatology, Guy’s and St Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, U.K.
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  • A. Ranki,

    1. Department of Dermatology, University of Copenhagen, Bispebjerg Hospital, Bispebjerg bakke 23, DK-2400 Copenhagen, Denmark
      *Department of Dermatology and Allergy, Skin Cancer Center Charité, Charité-Universitätsmedizin Berlin, Schumannstrasse 20/21, 10117 Berlin, Germany
      †Department of Dermatology, AP-HP, Hôpital Henri Mondor, INSERM, U 659, University Paris 12, F-94010 Créteil, France
      ‡Department of Dermatology, University Hospital of Zurich, Gloriastrasse 31, CH-8091 Zurich, Switzerland
      §Department of Dermatology, University of Texas M.D. Anderson Cancer Center, Box 434, 1515 Holcombe Boulevard, Houston, TX 77030, U.S.A.
      ¶Department of Dermatology, Division of Special and Environmental Dermatology, Medical University of Vienna, Währingergürtel 18–20, A-1090 Vienna, Austria
      **Skin and Allergy Hospital, Helsinki University Hospital, PO Box 160, 00029 HUS Helsinki, Finland
      ††Arteriosklerose-Präventions-Institut München, Wilbrechtstrasse 95, D-81477 Munich, Germany
      ‡‡St John’s Institute of Dermatology, Guy’s and St Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, U.K.
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  • P. Schwandt,

    1. Department of Dermatology, University of Copenhagen, Bispebjerg Hospital, Bispebjerg bakke 23, DK-2400 Copenhagen, Denmark
      *Department of Dermatology and Allergy, Skin Cancer Center Charité, Charité-Universitätsmedizin Berlin, Schumannstrasse 20/21, 10117 Berlin, Germany
      †Department of Dermatology, AP-HP, Hôpital Henri Mondor, INSERM, U 659, University Paris 12, F-94010 Créteil, France
      ‡Department of Dermatology, University Hospital of Zurich, Gloriastrasse 31, CH-8091 Zurich, Switzerland
      §Department of Dermatology, University of Texas M.D. Anderson Cancer Center, Box 434, 1515 Holcombe Boulevard, Houston, TX 77030, U.S.A.
      ¶Department of Dermatology, Division of Special and Environmental Dermatology, Medical University of Vienna, Währingergürtel 18–20, A-1090 Vienna, Austria
      **Skin and Allergy Hospital, Helsinki University Hospital, PO Box 160, 00029 HUS Helsinki, Finland
      ††Arteriosklerose-Präventions-Institut München, Wilbrechtstrasse 95, D-81477 Munich, Germany
      ‡‡St John’s Institute of Dermatology, Guy’s and St Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, U.K.
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  • S. Whittaker

    1. Department of Dermatology, University of Copenhagen, Bispebjerg Hospital, Bispebjerg bakke 23, DK-2400 Copenhagen, Denmark
      *Department of Dermatology and Allergy, Skin Cancer Center Charité, Charité-Universitätsmedizin Berlin, Schumannstrasse 20/21, 10117 Berlin, Germany
      †Department of Dermatology, AP-HP, Hôpital Henri Mondor, INSERM, U 659, University Paris 12, F-94010 Créteil, France
      ‡Department of Dermatology, University Hospital of Zurich, Gloriastrasse 31, CH-8091 Zurich, Switzerland
      §Department of Dermatology, University of Texas M.D. Anderson Cancer Center, Box 434, 1515 Holcombe Boulevard, Houston, TX 77030, U.S.A.
      ¶Department of Dermatology, Division of Special and Environmental Dermatology, Medical University of Vienna, Währingergürtel 18–20, A-1090 Vienna, Austria
      **Skin and Allergy Hospital, Helsinki University Hospital, PO Box 160, 00029 HUS Helsinki, Finland
      ††Arteriosklerose-Präventions-Institut München, Wilbrechtstrasse 95, D-81477 Munich, Germany
      ‡‡St John’s Institute of Dermatology, Guy’s and St Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, U.K.
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  • Conflicts of interest
    The authors received an honorarium from Cephalon Europe for their advisory role in the development of the manuscript; however, the company did not participate in the preparation of the manuscript or influence its content. Madeleine Duvic has been principal investigator on clinical trials for Ligand Pharmaceuticals and Reinhard Dummer holds an unrestricted research grant from the company. Madeleine Duvic, Robert Knobler and Reinhard Dummer have all acted as consultants for Ligand.

Robert Gniadecki.
E-mail: rg01@bbh.hosp.dk

Summary

The management goal in cutaneous T-cell lymphomas (CTCLs) is to improve symptoms and induce remission. Early-stage disease is generally treated with skin-directed therapies. However, if these do not control the disease, systemic therapy becomes necessary. Bexarotene, a novel rexinoid, is an oral, noncytotoxic drug that has been approved in Europe for the treatment of refractory advanced-stage CTCL and in the U.S.A. for refractory CTCL. We provide guidance on the use of bexarotene in the management of CTCL, based on data from phase II/III clinical trials and the authors’ clinical experience, and suggest how the potential of the drug can be maximized. The clinical trial results with bexarotene are reviewed, especially in comparison with interferon-α, which is the other commonly used noncytotoxic systemic therapy for CTCL. A treatment algorithm for bexarotene in refractory CTCL is suggested. As bexarotene may take time to achieve a maximum response, this algorithm recommends that therapy should be continued for a sufficient period to allow for a delayed onset of action. In addition, possible combination therapies with bexarotene are discussed. We conclude that bexarotene is effective in the management of CTCL, and has the advantage of oral administration. An on-going randomized clinical trial comparing psoralen plus ultraviolet A (PUVA) with PUVA plus bexarotene will provide valuable information about this combination regimen in early-stage disease, but further data are needed on the relative efficacies of other combination therapies with bexarotene in CTCL.

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