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Resident’s Forum
RF-New Evidence in Favor of 5-Fluorouracil in the Treatment of Actinic Keratosis
FR-Nueva evidencia a favor de 5-fluorouracilo en eltratamiento de las queratosis actínicas
D. Morgado-Carrasco
Corresponding author
morgado@clinic.cat

Corresponding author.
, X. Fustà-Novell, A. Toll
Servicio de Dermatología, Hospital Clínic de Barcelona, Barcelona, España
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        "titulo" => "FR-Nueva evidencia a favor de 5-fluorouracilo en eltratamiento de las queratosis act&#237;nicas"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Actinic keratosis &#40;AK&#41; is a highly prevalent premalignant lesion&#46; The risk of progression to squamous cell carcinoma varies between 0&#37; and 0&#46;53&#37; per AK lesion per year&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> A wide variety of therapeutic options are available&#46; Cryotherapy and curettage are among the options available for isolated lesions&#46; However&#44; it is relatively common for patients to present field cancerization&#44; requiring treatment of the entire area&#44; including 5-fluorouracil &#40;5-FU&#41;&#44; imiquimod&#44; ingenol mebutate&#44; or photodynamic therapy &#40;PDT&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> Evidence regarding which is the most effective treatment is scarce&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Recently&#44; Jansen et al<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> published the results of the first multicenter randomized&#44; blind clinical trial &#40;n&#8239;&#61;&#8239;624&#41;&#44; performed in the Netherlands&#44; which compared 5-FU 5&#37; &#40;n&#8239;&#61;&#8239;155&#41; &#40;applied twice daily for 4 weeks&#41;&#44; imiquimod 5&#37; &#40;n&#8239;&#61;&#8239;156&#41;&#44; ingenol mebutate 0&#46;015&#37; &#40;n&#8239;&#61;&#8239;157&#41;&#44; and PDT with methyl aminolevulinate &#40;PDT-MAL&#41; &#40;n&#8239;&#61;&#8239;156&#41;&#46; Imiquimod&#44; ingenol mebutate&#44; and PDT-MAL were used in accordance with the product information sheet&#46; The study included adults with 5 AK lesions or more &#40;of any grade&#41; in an area of between 25 and 100&#8239;cm<span class="elsevierStyleSup">2</span> on the head or neck&#46; Immunocompromised individuals were excluded from the study&#46; In the first visit&#44; a transparent sheet was drawn over the exact position of the AK lesions to allow for an accurate follow-up&#46; Patients were able to receive up to 2 treatment cycles&#46; The main objective was to evaluate a reduction of 75&#37; or more in the AK lesions after 12 months&#46; Therapeutic failure was defined as failure to achieve this percentage&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">An intention-to-treat analysis was performed on the 602 patients with available clinical-response data&#46; The probability of not presenting treatment failure was 74&#46;7&#37; &#40;confidence interval &#91;CI&#93;&#44; 66&#46;8&#8211;81&#41; with 5-FU&#44; 53&#46;9&#37; &#40;CI&#44; 66&#46;8&#8211;81&#41; with imiquimod&#44; 37&#46;7&#37; &#40;CI&#44; 30&#8211;45&#46;3&#41; with PDT-MAL&#44; and 28&#46;9&#37; &#40;CI&#44; 21&#46;8&#8211;36&#46;3&#41; with ingenol mebutate&#46; The differences between 5-FU and the other treatments were statistically significant&#46; The per-protocol analysis showed similar results&#46; The relative risk of therapeutic failure when compared with 5-FU &#40;hazard ratio&#8239;&#61;&#8239;1&#41; was 2&#46;03 with imiquimod&#44; 2&#46;73 with PDT-MAL&#44; and 3&#46;33 with ingenol mebutate&#46; Satisfaction with treatment and improved quality of life was higher with 5-FU than with the other drugs &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Treatment failure after the first treatment cycle was observed in 14&#46;8&#37; with 5-FU&#44; in 37&#46;2&#37; with imiquimod&#44; 34&#46;6&#37; with PDT-MAL&#44; and 47&#46;8&#37; with ingenol mebutate&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Adherence to treatment exceeded 88&#37; with all treatments&#46; The rate of adverse effects was similar in all groups&#46; However&#44; PDT-MAL was associated with more pain&#46; No associated severe adverse effects were observed and none of the patients suspended the drug for this reason&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">This study shows that 5-FU may be superior and have no more adverse effects than other therapeutic alternatives&#44; and patients present a high degree of satisfaction&#46; One of the disadvantages in Spain is the lack of a commercial presentation of 5&#37; 5-FU&#44; which makes it necessary to formulate the drug and may limit its prescription&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">5-FU is an effective&#44; safe&#44; and economical alternative in the management of AK&#46; This new evidence demonstrates its superiority to imiquimod&#44; PDT-MAL&#44; and ingenol mebutate&#46;</p></span>"
    "pdfFichero" => "main.pdf"
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    "fechaRecibido" => "2019-04-03"
    "fechaAceptado" => "2019-04-21"
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Morgado-Carrasco D&#44; Fust&#224;-Novell X&#44; Toll A&#46; FR-Nueva evidencia a favor de 5-fluorouracilo en eltratamiento de lasqueratosis act&#237;nicas&#46; Actas Dermosifiliogr&#46; 2021&#59;112&#58;69&#8211;70&#46;</p>"
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          "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Abbreviation&#58; AK indicates actinic keratosis&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
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                  \t\t\t\t ; entry_with_role_rowhead " rowspan="3" align="left" valign="\n
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                  \t\t\t\t">Dosage and duration of treatment</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">5&#37; concentration&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Application twice daily for 4 weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Up to 2 treatment cycles&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Reduction &#8805;75&#37; of AK lesions after 12 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">In 82&#46;4&#37; of cases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients who would recommend the treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">83&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients who would undergo retreatment if necessary&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">86&#46;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Good or excellent cosmetic result&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90&#46;3&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t">Adverse effects</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Moderate or severe erythema &#40;81&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Moderate or severe erosions &#40;40&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Moderate or severe pain &#40;31&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                      "titulo" => "Evidence- and consensus-based &#40;S3&#41; Guidelines for the Treatment of Actinic Keratosis - International League of Dermatological Societies in cooperation with the European Dermatology Forum - Short version"
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                        0 => array:2 [
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                          "autores" => array:6 [
                            0 => "R&#46;N&#46; Werner"
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                            2 => "S&#46;M&#46; Connolly"
                            3 => "O&#46; Correia"
                            4 => "R&#46; Erdmann"
                            5 => "P&#46; Foley"
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                        "tituloSerie" => "J Eur Acad Dermatol Venereol"
                        "fecha" => "2015"
                        "volumen" => "29"
                        "paginaInicial" => "2069"
                        "paginaFinal" => "2079"
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26370093"
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                          "autores" => array:6 [
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                            2 => "A&#46; Garc&#237;a-Diez"
                            3 => "C&#46; Guill&#233;n-Barona"
                            4 => "I&#46; Belinch&#243;n-Romero"
                            5 => "P&#46; Redondo-Bell&#243;n"
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                      "doi" => "10.1016/j.adengl.2013.11.004"
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                            3 => "N&#46; Kouloubis"
                            4 => "A&#46;H&#46;M&#46;M&#46; Arits"
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Article information
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Idiomas
Actas Dermo-Sifiliográficas
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