title: Mapisal Versus Urea Cream as Prophylaxis for Capecitabine-Associated Hand-Foot Syndrome: A Randomized Phase III Trial of the AIO Quality of Life Working Group.
abstract: OBJECTIVE
  Hand-foot syndrome (HFS) is a frequently occurring adverse event associated with anticancer drugs. This study compares a newly introduced ointment containing several antioxidants and exhibiting high radical protection factor, which has been available on the German market since 2011, with urea cream for prevention of HFS in patients treated with capecitabine.
  
  
  METHODS
  Patients with GI tumors or breast cancer treated with capecitabine were included in this randomized phase III study. The primary end point was prevention of HFS of any grade within 6 weeks of treatment as indicated by a standardized patient diary. The study had 80% power to show a 20% reduction of the incidence of HFS with the new ointment. Secondary end points included time to development of HFS greater than grade 1, evaluation of capecitabine dose intensity, and quality of life analyses.
  
  
  RESULTS
  A total of 152 patients were evaluable. In total, 47 of 152 patients experienced HFS (30.9%), 39.5% with the new ointment and 22.4% in the urea arm (stratified odds ratio, 2.37; P = .02). Time to HFS greater than grade 1 was comparable, but time to any-grade HFS was significantly longer in the urea group (P = .03). Capecitabine dose intensity, time under study, and percentage of days with correct administration of study medication were identical, as were adverse events except for HFS. Skin-related quality of life was significantly worse in the group treated with the new ointment at the end of study treatment.
  
  
  CONCLUSIONS
  This trial demonstrated that 10% urea cream was superior to the new ointment at preventing HFS over the first 6 weeks of treatment with capecitabine.
authors.affiliation: Ralf-Dieter Hofheinz and Deniz Gencer, University Hospital Mannheim, Mannheim; Holger Schulz, Praxis Internistische Onkologie und Hämatologie, Frechen; Michael Stahl, Kliniken Essen-Mitte, Essen; Susanna Hegewisch-Becker, Hämatologisch-Onkologische Praxis Eppendorf, Hamburg; Luisa Mantovani Loeffler, Onkologie, Haematologie und Palliativmedizin, Leipzig; Ursula Kronawitter, Onkologische Schwerpunktpraxis, Traunstein; Georg Bolz, Medizinische Klinik I, Ludwigshafen; Jochem Potenberg, Waldkrankenhaus Spandau, Berlin; Felix Tauchert and Salah-Eddin Al-Batran, Krankenhaus Nordwest, UCT-University Cancer Center, Frankfurt am Main; and Andreas Schneeweiss, University of Heidelberg, Heidelberg, Germany Ralf-Dieter.Hofheinz@medma.uni-heidelberg.de.
authors.forename: Ralf-Dieter
authors.initials: RD
authors.lastname: Hofheinz
authors.affiliation: Ralf-Dieter Hofheinz and Deniz Gencer, University Hospital Mannheim, Mannheim; Holger Schulz, Praxis Internistische Onkologie und Hämatologie, Frechen; Michael Stahl, Kliniken Essen-Mitte, Essen; Susanna Hegewisch-Becker, Hämatologisch-Onkologische Praxis Eppendorf, Hamburg; Luisa Mantovani Loeffler, Onkologie, Haematologie und Palliativmedizin, Leipzig; Ursula Kronawitter, Onkologische Schwerpunktpraxis, Traunstein; Georg Bolz, Medizinische Klinik I, Ludwigshafen; Jochem Potenberg, Waldkrankenhaus Spandau, Berlin; Felix Tauchert and Salah-Eddin Al-Batran, Krankenhaus Nordwest, UCT-University Cancer Center, Frankfurt am Main; and Andreas Schneeweiss, University of Heidelberg, Heidelberg, Germany.
authors.forename: Deniz
authors.initials: D
authors.lastname: Gencer
authors.affiliation: Ralf-Dieter Hofheinz and Deniz Gencer, University Hospital Mannheim, Mannheim; Holger Schulz, Praxis Internistische Onkologie und Hämatologie, Frechen; Michael Stahl, Kliniken Essen-Mitte, Essen; Susanna Hegewisch-Becker, Hämatologisch-Onkologische Praxis Eppendorf, Hamburg; Luisa Mantovani Loeffler, Onkologie, Haematologie und Palliativmedizin, Leipzig; Ursula Kronawitter, Onkologische Schwerpunktpraxis, Traunstein; Georg Bolz, Medizinische Klinik I, Ludwigshafen; Jochem Potenberg, Waldkrankenhaus Spandau, Berlin; Felix Tauchert and Salah-Eddin Al-Batran, Krankenhaus Nordwest, UCT-University Cancer Center, Frankfurt am Main; and Andreas Schneeweiss, University of Heidelberg, Heidelberg, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Schulz
authors.affiliation: Ralf-Dieter Hofheinz and Deniz Gencer, University Hospital Mannheim, Mannheim; Holger Schulz, Praxis Internistische Onkologie und Hämatologie, Frechen; Michael Stahl, Kliniken Essen-Mitte, Essen; Susanna Hegewisch-Becker, Hämatologisch-Onkologische Praxis Eppendorf, Hamburg; Luisa Mantovani Loeffler, Onkologie, Haematologie und Palliativmedizin, Leipzig; Ursula Kronawitter, Onkologische Schwerpunktpraxis, Traunstein; Georg Bolz, Medizinische Klinik I, Ludwigshafen; Jochem Potenberg, Waldkrankenhaus Spandau, Berlin; Felix Tauchert and Salah-Eddin Al-Batran, Krankenhaus Nordwest, UCT-University Cancer Center, Frankfurt am Main; and Andreas Schneeweiss, University of Heidelberg, Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Stahl
authors.affiliation: Ralf-Dieter Hofheinz and Deniz Gencer, University Hospital Mannheim, Mannheim; Holger Schulz, Praxis Internistische Onkologie und Hämatologie, Frechen; Michael Stahl, Kliniken Essen-Mitte, Essen; Susanna Hegewisch-Becker, Hämatologisch-Onkologische Praxis Eppendorf, Hamburg; Luisa Mantovani Loeffler, Onkologie, Haematologie und Palliativmedizin, Leipzig; Ursula Kronawitter, Onkologische Schwerpunktpraxis, Traunstein; Georg Bolz, Medizinische Klinik I, Ludwigshafen; Jochem Potenberg, Waldkrankenhaus Spandau, Berlin; Felix Tauchert and Salah-Eddin Al-Batran, Krankenhaus Nordwest, UCT-University Cancer Center, Frankfurt am Main; and Andreas Schneeweiss, University of Heidelberg, Heidelberg, Germany.
authors.forename: Susanna
authors.initials: S
authors.lastname: Hegewisch-Becker
authors.affiliation: Ralf-Dieter Hofheinz and Deniz Gencer, University Hospital Mannheim, Mannheim; Holger Schulz, Praxis Internistische Onkologie und Hämatologie, Frechen; Michael Stahl, Kliniken Essen-Mitte, Essen; Susanna Hegewisch-Becker, Hämatologisch-Onkologische Praxis Eppendorf, Hamburg; Luisa Mantovani Loeffler, Onkologie, Haematologie und Palliativmedizin, Leipzig; Ursula Kronawitter, Onkologische Schwerpunktpraxis, Traunstein; Georg Bolz, Medizinische Klinik I, Ludwigshafen; Jochem Potenberg, Waldkrankenhaus Spandau, Berlin; Felix Tauchert and Salah-Eddin Al-Batran, Krankenhaus Nordwest, UCT-University Cancer Center, Frankfurt am Main; and Andreas Schneeweiss, University of Heidelberg, Heidelberg, Germany.
authors.forename: Luisa Mantovani
authors.initials: LM
authors.lastname: Loeffler
authors.affiliation: Ralf-Dieter Hofheinz and Deniz Gencer, University Hospital Mannheim, Mannheim; Holger Schulz, Praxis Internistische Onkologie und Hämatologie, Frechen; Michael Stahl, Kliniken Essen-Mitte, Essen; Susanna Hegewisch-Becker, Hämatologisch-Onkologische Praxis Eppendorf, Hamburg; Luisa Mantovani Loeffler, Onkologie, Haematologie und Palliativmedizin, Leipzig; Ursula Kronawitter, Onkologische Schwerpunktpraxis, Traunstein; Georg Bolz, Medizinische Klinik I, Ludwigshafen; Jochem Potenberg, Waldkrankenhaus Spandau, Berlin; Felix Tauchert and Salah-Eddin Al-Batran, Krankenhaus Nordwest, UCT-University Cancer Center, Frankfurt am Main; and Andreas Schneeweiss, University of Heidelberg, Heidelberg, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Kronawitter
authors.affiliation: Ralf-Dieter Hofheinz and Deniz Gencer, University Hospital Mannheim, Mannheim; Holger Schulz, Praxis Internistische Onkologie und Hämatologie, Frechen; Michael Stahl, Kliniken Essen-Mitte, Essen; Susanna Hegewisch-Becker, Hämatologisch-Onkologische Praxis Eppendorf, Hamburg; Luisa Mantovani Loeffler, Onkologie, Haematologie und Palliativmedizin, Leipzig; Ursula Kronawitter, Onkologische Schwerpunktpraxis, Traunstein; Georg Bolz, Medizinische Klinik I, Ludwigshafen; Jochem Potenberg, Waldkrankenhaus Spandau, Berlin; Felix Tauchert and Salah-Eddin Al-Batran, Krankenhaus Nordwest, UCT-University Cancer Center, Frankfurt am Main; and Andreas Schneeweiss, University of Heidelberg, Heidelberg, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Bolz
authors.affiliation: Ralf-Dieter Hofheinz and Deniz Gencer, University Hospital Mannheim, Mannheim; Holger Schulz, Praxis Internistische Onkologie und Hämatologie, Frechen; Michael Stahl, Kliniken Essen-Mitte, Essen; Susanna Hegewisch-Becker, Hämatologisch-Onkologische Praxis Eppendorf, Hamburg; Luisa Mantovani Loeffler, Onkologie, Haematologie und Palliativmedizin, Leipzig; Ursula Kronawitter, Onkologische Schwerpunktpraxis, Traunstein; Georg Bolz, Medizinische Klinik I, Ludwigshafen; Jochem Potenberg, Waldkrankenhaus Spandau, Berlin; Felix Tauchert and Salah-Eddin Al-Batran, Krankenhaus Nordwest, UCT-University Cancer Center, Frankfurt am Main; and Andreas Schneeweiss, University of Heidelberg, Heidelberg, Germany.
authors.forename: Jochem
authors.initials: J
authors.lastname: Potenberg
authors.affiliation: Ralf-Dieter Hofheinz and Deniz Gencer, University Hospital Mannheim, Mannheim; Holger Schulz, Praxis Internistische Onkologie und Hämatologie, Frechen; Michael Stahl, Kliniken Essen-Mitte, Essen; Susanna Hegewisch-Becker, Hämatologisch-Onkologische Praxis Eppendorf, Hamburg; Luisa Mantovani Loeffler, Onkologie, Haematologie und Palliativmedizin, Leipzig; Ursula Kronawitter, Onkologische Schwerpunktpraxis, Traunstein; Georg Bolz, Medizinische Klinik I, Ludwigshafen; Jochem Potenberg, Waldkrankenhaus Spandau, Berlin; Felix Tauchert and Salah-Eddin Al-Batran, Krankenhaus Nordwest, UCT-University Cancer Center, Frankfurt am Main; and Andreas Schneeweiss, University of Heidelberg, Heidelberg, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Tauchert
authors.affiliation: Ralf-Dieter Hofheinz and Deniz Gencer, University Hospital Mannheim, Mannheim; Holger Schulz, Praxis Internistische Onkologie und Hämatologie, Frechen; Michael Stahl, Kliniken Essen-Mitte, Essen; Susanna Hegewisch-Becker, Hämatologisch-Onkologische Praxis Eppendorf, Hamburg; Luisa Mantovani Loeffler, Onkologie, Haematologie und Palliativmedizin, Leipzig; Ursula Kronawitter, Onkologische Schwerpunktpraxis, Traunstein; Georg Bolz, Medizinische Klinik I, Ludwigshafen; Jochem Potenberg, Waldkrankenhaus Spandau, Berlin; Felix Tauchert and Salah-Eddin Al-Batran, Krankenhaus Nordwest, UCT-University Cancer Center, Frankfurt am Main; and Andreas Schneeweiss, University of Heidelberg, Heidelberg, Germany.
authors.forename: Salah-Eddin
authors.initials: SE
authors.lastname: Al-Batran
authors.affiliation: Ralf-Dieter Hofheinz and Deniz Gencer, University Hospital Mannheim, Mannheim; Holger Schulz, Praxis Internistische Onkologie und Hämatologie, Frechen; Michael Stahl, Kliniken Essen-Mitte, Essen; Susanna Hegewisch-Becker, Hämatologisch-Onkologische Praxis Eppendorf, Hamburg; Luisa Mantovani Loeffler, Onkologie, Haematologie und Palliativmedizin, Leipzig; Ursula Kronawitter, Onkologische Schwerpunktpraxis, Traunstein; Georg Bolz, Medizinische Klinik I, Ludwigshafen; Jochem Potenberg, Waldkrankenhaus Spandau, Berlin; Felix Tauchert and Salah-Eddin Al-Batran, Krankenhaus Nordwest, UCT-University Cancer Center, Frankfurt am Main; and Andreas Schneeweiss, University of Heidelberg, Heidelberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schneeweiss
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D000975:Antioxidants / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy; D005858:Germany; D060831:Hand-Foot Syndrome / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D015994:Incidence; D007641:Keratolytic Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009824:Ointments; D011322:Primary Prevention / Q000379:methods*; D011788:Quality of Life; D012720:Severity of Illness Index; D063465:Skin Cream; D011795:Surveys and Questionnaires; D013997:Time Factors; D017211:Treatment Failure; D014508:Urea / Q000008:administration & dosage*
chemical_list: D000964:Antimetabolites, Antineoplastic; D000975:Antioxidants; D007641:Keratolytic Agents; D009824:Ointments; D003841:Deoxycytidine; D000069287:Capecitabine; D014508:Urea; D005472:Fluorouracil