title: Systematic review of combination therapies for mycosis fungoides.
abstract: BACKGROUND
  A variety of therapeutic options are available for mycosis fungoides, the most prevalent subtype of cutaneous T cell lymphomas, but thus far, no regimen has been proven to be curative. A combination of treatments is a well-established strategy to increase the therapeutic efficacy. However, data from clinical trials analyzing such combinations for the treatment of mycosis fungoides are scarce.
  
  
  OBJECTIVE
  To analyze the available evidence on combination therapies with emphasis on the combination of psoralen with UVA phototherapy (PUVA), interferon-alpha and bexarotene with another treatment.
  
  
  METHODS
  Systematic literature review of the databases Embase, Cochrane, Medline, and Medline in Process.
  
  
  RESULTS
  Combination of PUVA with interferon-alpha or retinoids did not result in an increased overall response rate. Addition of methotrexate but not retinoids to interferon-alpha may increase the overall response rate. Bexarotene was investigated in one trial each with vorinostat, methotrexate or gemcitabine, whereby only methotrexate possibly enhanced the effect of bexarotene.
  
  
  CONCLUSIONS
  For mycosis fungoides, no combination treatment has been demonstrated to be superior to monotherapy. Based on our analysis, we conclude that in certain clinical situations, patients may benefit from a combination of PUVA with interferon-alpha or a retinoid or a combination of the latter two. Furthermore, patients in advanced stages may benefit from the combination of methotrexate and interferon-alpha or bexarotene. Finally, the combination of bexarotene with either vorinostat or gemcitabine did not increase the overall response rate but resulted in more pronounced side effects and cannot be recommended.
authors.affiliation: Klinik für Dermatologie, Venerologie und Allergologie, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: daniel.humme@charite.de.
authors.forename: Daniel
authors.initials: D
authors.lastname: Humme
authors.affiliation: Klinik für Dermatologie, Venerologie und Allergologie, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: alexander.nast@charite.de.
authors.forename: Alexander
authors.initials: A
authors.lastname: Nast
authors.affiliation: Klinik für Dermatologie, Venerologie und Allergologie, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: ricardo.erdmann@charite.de.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Erdmann
authors.affiliation: Klinik für Dermatologie, Venerologie und Allergologie, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: staffan.vandersee@charite.de.
authors.forename: Staffan
authors.initials: S
authors.lastname: Vandersee
authors.affiliation: Klinik für Dermatologie, Venerologie und Allergologie, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: marc.beyer@charite.de.
authors.forename: Marc
authors.initials: M
authors.lastname: Beyer
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077610:Bexarotene; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005363:Ficusin / Q000008:administration & dosage; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage; D016898:Interferon-alpha / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage; D009182:Mycosis Fungoides / Q000188:drug therapy / Q000628:therapy*; D010789:Phototherapy / Q000379:methods*; D012176:Retinoids / Q000008:administration & dosage; D012878:Skin Neoplasms / Q000188:drug therapy / Q000628:therapy*; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage; D000077337:Vorinostat; D000093542:Gemcitabine
chemical_list: D006877:Hydroxamic Acids; D016898:Interferon-alpha; D012176:Retinoids; D013764:Tetrahydronaphthalenes; D003841:Deoxycytidine; D000077337:Vorinostat; D000077610:Bexarotene; D005363:Ficusin; D008727:Methotrexate; D000093542:Gemcitabine
keywords: Bexarotene; Combination therapy; Interferon-alpha; Mycosis fungoides; Puva; Systematic review