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RF - Pharmacological Prevention of Nonmelanoma Skin Cancer in High-Risk Patients
FR - Prevención farmacológica del cáncer cutáneo no-melanoma en pacientes de alto riesgo
X. Bosch-Amate
, D. Morgado-Carrasco, N. Martínez
Corresponding author
Servicio de Dermatología, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain
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Bosch-Amate, D. Morgado-Carrasco, N. Martínez" "autores" => array:3 [ 0 => array:4 [ "nombre" => "X." "apellidos" => "Bosch-Amate" "email" => array:1 [ 0 => "xavi_bosch92@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "D." "apellidos" => "Morgado-Carrasco" ] 2 => array:2 [ "nombre" => "N." "apellidos" => "Martínez" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Dermatología, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "FR - Prevención farmacológica del cáncer cutáneo no-melanoma en pacientes de alto riesgo" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Nonmelanoma skin cancer (NMSC) is the most common neoplasia in humans. It includes basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Its main risk factors are accumulated exposure to sunlight, immunosuppression, and infection with the beta human papillomavirus. The use of topical sunscreen is frequently indicated in secondary prevention. In recent years, new evidence supports the use of some drugs as chemoprophylactics (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">A randomized double-blind clinical trial in 932 high-risk patients (98% Caucasian males, with a mean age of 71 years) was recently published. Chemoprevention was studied using a cycle of 5% topical fluorouracil (every 12<span class="elsevierStyleHsp" style=""></span>h for 4 weeks) (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>468) versus placebo (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>464) on the appearance of NMSC of the face and ears with surgical indication. In the first year after treatment a lower number of SCC was detected (1% versus 4%) (risk reduction of 75% [95% CI, 35%–91%] [<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.002]). No differences were found in BCC (10% versus 11%), although the number of Mohs surgeries in the first year dropped. After 4 years of follow-up, no differences were found in the number of SCC or BCC between the 2 groups (39% versus 38%). In terms of adverse effects, 92% of the group receiving fluorouracil presented erythema (21% described it as severe), but 85% would use the treatment again if necessary.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> These results suggest that a cycle of topical fluorouracil would be useful in secondary prevention of SCC for a year. It remains to be demonstrated whether an annual cycle of 5% topical fluorouracil is an effective long-term strategy. We must remember that 5-fluoracil is not sold in Spain and must be formulated. This may limit its potential use in Spain.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Previously, a phase-III randomized, double-blind, placebo-controlled clinical trial in 386 high-risk patients had demonstrated the efficacy of oral nicotinamide (500<span class="elsevierStyleHsp" style=""></span>mg/12<span class="elsevierStyleHsp" style=""></span>h of vitamin B3) as chemoprevention for NMSC. In the 12 months that the nicotinamide was used, the number of NMSC per person was reduced (1.8 versus 2.4), with a risk reduction of 23% (95% CI, 4%–38%) (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.02), and the drug was well tolerated. This protective effect was lost 6 months after the treatment ended.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Oral retinoids have been shown to be of use in chemoprevention of NMSC while they are being used. In a randomized, placebo-controlled clinical trial (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2297), the risk of SCC was lower among those who received 25,000<span class="elsevierStyleHsp" style=""></span>IU/d of retinol (vitamin A) (hazard ratio, 0.74 [95% CI, 0.56–0.99] [<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.04]).<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> Other smaller studies have shown the efficacy of isotretinoin and oral acitretin in reducing the risk of NMSC, but with greater toxicity.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">2,4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Other oral drugs studied include capecitabin, celecoxib, and ibuprofen, but greater evidence is required for their use to be recommended. Most of the above-mentioned treatments have demonstrated efficacy in preventing SCC but not BCC. This may be explained by their different etiologies, including the fact that UV radiation damage and viral infection are not as important in BCC. In terms of treatment of NMSC precursor lesions, different topical agents have been shown to be effective, such as ingenol mebutate, imiquimod, and diclofenac. Photodynamic therapy is also highly effective in the treatment of these lesions.</p><p id="par0030" class="elsevierStylePara elsevierViewall">In solid-organ transplant and immunosuppressed patients, it is important to reduce immunosuppression to the minimum effective dose and to replace calcineurin inhibitors (cyclosporin and tacrolimus) with mTOR inhibitors (sirolimus or everolimus). The use of sirolimus has been associated with a significant reduction in the risk of NMSC.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Different pharmacological options exist for patients with a high risk of developing NMSC, such as 5% topical fluorouracil, retinoids, and oral nicotinamide to reduce this risk and the associated morbidity and mortality.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1273668" "palabras" => array:5 [ 0 => "Basal cell carcinoma" 1 => "Squamous cell carcinoma" 2 => "Skin cancer" 3 => "Prevention" 4 => "5-Fluorouracil" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "⋆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Bosch-Amate X, Morgado-Carrasco D, Martínez N. FR - Prevención farmacológica del cáncer cutáneo no-melanoma en pacientes de alto riesgo. Actas Dermosifiliogr. 2020;111:609–610.</p>" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: SCC indicates squamous cell carcinoma; NMSC, nonmelanoma skin cancer; RCT, randomized clinical trial; AK, actinic keratosis.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Drug \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Route of Administration \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dosage \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Evidence in Favor \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><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">5-Fluorouracil \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">Topical, 5% \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">Twice daily for 4 weeks (an annual cycle?) \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">RCT in high-risk patients (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>932). Reduced rate of SCC in the 1st year<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> \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">Retinol \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">Oral \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">25,000<span class="elsevierStyleHsp" style=""></span>IU/day for 5 years \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">RCT in high-risk patients (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2297). Reduced risk of SCC while treatment lasted<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> \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">Acitretin \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">Oral \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">30<span class="elsevierStyleHsp" style=""></span>mg/day for 6 months \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">RCT in kidney-transplant patients (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>44). Reduced risk of NMSC while treatment lasted<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> \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">Nicotinamide \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">Oral \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">500<span class="elsevierStyleHsp" style=""></span>mg twice daily for a year \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">RCT in high-risk patients (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>386). Reduced risk of NMSC and AK while treatment lasted<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2383104.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Drugs Used in Secondary Prevention of Nonmelanoma Skin Cancer.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chemoprevention of basal and squamous cell carcinoma with a single course of fluorouracil, 5%, cream: a randomized clinical trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.A. Weinstock" 1 => "S.S. Thwin" 2 => "J.A. Siegel" 3 => "K. Marcolivio" 4 => "A.D. Means" 5 => "N.F. Leader" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/jamadermatol.2017.3631" "Revista" => array:6 [ "tituloSerie" => "JAMA Dermatol" "fecha" => "2018" "volumen" => "154" "paginaInicial" => "167" "paginaFinal" => "174" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29299592" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A phase 3 randomized trial of nicotinamide for skin-cancer chemoprevention" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.C. Chen" 1 => "A.J. Martin" 2 => "B. Choy" 3 => "P. Fernández-Peñas" 4 => "R.A. Dalziell" 5 => "C.A. 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Hermans" 5 => "J. ter Schegget" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.1995.13.8.1933" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "1995" "volumen" => "13" "paginaInicial" => "1933" "paginaFinal" => "1938" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7636533" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sirolimus effects on cancer incidence after kidney transplantation: a meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "E.L. Yanik" 1 => "K. Siddiqui" 2 => "E.A. Engels" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/cam4.487" "Revista" => array:6 [ "tituloSerie" => "Cancer Med" "fecha" => "2015" "volumen" => "4" "paginaInicial" => "1448" "paginaFinal" => "1459" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26108799" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/15782190/0000011100000007/v1_202009190930/S1578219020302122/v1_202009190930/en/main.assets" "Apartado" => array:4 [ "identificador" => "34945" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Resident's Forum" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/15782190/0000011100000007/v1_202009190930/S1578219020302122/v1_202009190930/en/main.pdf?idApp=UINPBA000044&text.app=https://actasdermo.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219020302122?idApp=UINPBA000044" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 5 | 9 | 14 |
| 2024 October | 70 | 50 | 120 |
| 2024 September | 69 | 22 | 91 |
| 2024 August | 81 | 59 | 140 |
| 2024 July | 54 | 25 | 79 |
| 2024 June | 68 | 30 | 98 |
| 2024 May | 61 | 26 | 87 |
| 2024 April | 66 | 19 | 85 |
| 2024 March | 53 | 32 | 85 |
| 2024 February | 58 | 30 | 88 |
| 2024 January | 39 | 32 | 71 |
| 2023 December | 44 | 11 | 55 |
| 2023 November | 70 | 32 | 102 |
| 2023 October | 56 | 29 | 85 |
| 2023 September | 45 | 28 | 73 |
| 2023 August | 30 | 15 | 45 |
| 2023 July | 47 | 32 | 79 |
| 2023 June | 42 | 16 | 58 |
| 2023 May | 58 | 23 | 81 |
| 2023 April | 42 | 17 | 59 |
| 2023 March | 68 | 25 | 93 |
| 2023 February | 42 | 24 | 66 |
| 2023 January | 38 | 23 | 61 |
| 2022 December | 37 | 29 | 66 |
| 2022 November | 22 | 34 | 56 |
| 2022 October | 26 | 20 | 46 |
| 2022 September | 22 | 32 | 54 |
| 2022 August | 28 | 41 | 69 |
| 2022 July | 43 | 34 | 77 |
| 2022 June | 31 | 25 | 56 |
| 2022 May | 42 | 35 | 77 |
| 2022 April | 38 | 25 | 63 |
| 2022 March | 48 | 46 | 94 |
| 2022 February | 30 | 21 | 51 |
| 2022 January | 39 | 53 | 92 |
| 2021 December | 30 | 44 | 74 |
| 2021 November | 36 | 46 | 82 |
| 2021 October | 63 | 54 | 117 |
| 2021 September | 37 | 43 | 80 |
| 2021 August | 32 | 34 | 66 |
| 2021 July | 23 | 22 | 45 |
| 2021 June | 24 | 26 | 50 |
| 2021 May | 30 | 45 | 75 |
| 2021 April | 96 | 77 | 173 |
| 2021 March | 62 | 25 | 87 |
| 2021 February | 54 | 27 | 81 |
| 2021 January | 36 | 15 | 51 |
| 2020 December | 42 | 23 | 65 |
| 2020 November | 36 | 21 | 57 |
| 2020 October | 51 | 17 | 68 |
| 2020 September | 52 | 32 | 84 |
| 2020 August | 24 | 12 | 36 |
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