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topical fluorouracil &#40;every 12<span class="elsevierStyleHsp" style=""></span>h for 4 weeks&#41; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>468&#41; versus placebo &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>464&#41; on the appearance of NMSC of the face and ears with surgical indication&#46; In the first year after treatment a lower number of SCC was detected &#40;1&#37; versus 4&#37;&#41; &#40;risk reduction of 75&#37; &#91;95&#37; CI&#44; 35&#37;&#8211;91&#37;&#93; &#91;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;002&#93;&#41;&#46; No differences were found in BCC &#40;10&#37; versus 11&#37;&#41;&#44; although the number of Mohs surgeries in the first year dropped&#46; After 4 years of follow-up&#44; no differences were found in the number of SCC or BCC between the 2 groups &#40;39&#37; versus 38&#37;&#41;&#46; In terms of adverse effects&#44; 92&#37; of the group receiving fluorouracil presented erythema &#40;21&#37; described it as severe&#41;&#44; but 85&#37; would use the treatment again if necessary&#46;<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&#46; It remains to be demonstrated whether an annual cycle of 5&#37; topical fluorouracil is an effective long-term strategy&#46; We must remember that 5-fluoracil is not sold in Spain and must be formulated&#46; This may limit its potential use in Spain&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Previously&#44; a phase-III randomized&#44; double-blind&#44; placebo-controlled clinical trial in 386 high-risk patients had demonstrated the efficacy of oral nicotinamide &#40;500<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h of vitamin B3&#41; as chemoprevention for NMSC&#46; In the 12 months that the nicotinamide was used&#44; the number of NMSC per person was reduced &#40;1&#46;8 versus 2&#46;4&#41;&#44; with a risk reduction of 23&#37; &#40;95&#37; CI&#44; 4&#37;&#8211;38&#37;&#41; &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;02&#41;&#44; and the drug was well tolerated&#46; This protective effect was lost 6 months after the treatment ended&#46;<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&#46; In a randomized&#44; placebo-controlled clinical trial &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2297&#41;&#44; the risk of SCC was lower among those who received 25&#44;000<span class="elsevierStyleHsp" style=""></span>IU&#47;d of retinol &#40;vitamin A&#41; &#40;hazard ratio&#44; 0&#46;74 &#91;95&#37; CI&#44; 0&#46;56&#8211;0&#46;99&#93; &#91;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;04&#93;&#41;&#46;<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&#44; but with greater toxicity&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">2&#44;4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Other oral drugs studied include capecitabin&#44; celecoxib&#44; and ibuprofen&#44; but greater evidence is required for their use to be recommended&#46; Most of the above-mentioned treatments have demonstrated efficacy in preventing SCC but not BCC&#46; This may be explained by their different etiologies&#44; including the fact that UV radiation damage and viral infection are not as important in BCC&#46; In terms of treatment of NMSC precursor lesions&#44; different topical agents have been shown to be effective&#44; such as ingenol mebutate&#44; imiquimod&#44; and diclofenac&#46; Photodynamic therapy is also highly effective in the treatment of these lesions&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">In solid-organ transplant and immunosuppressed patients&#44; it is important to reduce immunosuppression to the minimum effective dose and to replace calcineurin inhibitors &#40;cyclosporin and tacrolimus&#41; with mTOR inhibitors &#40;sirolimus or everolimus&#41;&#46; The use of sirolimus has been associated with a significant reduction in the risk of NMSC&#46;<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&#44; such as 5&#37; topical fluorouracil&#44; retinoids&#44; and oral nicotinamide to reduce this risk and the associated morbidity and mortality&#46;</p></span>"
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dosage&nbsp;\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&nbsp;\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&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">Topical&#44; 5&#37;&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
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                  \t\t\t\t">Twice daily for 4 weeks &#40;an annual cycle&#63;&#41;&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">RCT in high-risk patients &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>932&#41;&#46; Reduced rate of SCC in the 1st year<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Retinol&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">Oral&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">RCT in high-risk patients &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2297&#41;&#46; Reduced risk of SCC while treatment lasted<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Acitretin&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">Oral&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
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                  \t\t\t\t">30<span class="elsevierStyleHsp" style=""></span>mg&#47;day for 6 months&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">RCT in kidney-transplant patients &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>44&#41;&#46; Reduced risk of NMSC while treatment lasted<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \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&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">500<span class="elsevierStyleHsp" style=""></span>mg twice daily for a year&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
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                  \t\t\t\t">RCT in high-risk patients &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>386&#41;&#46; Reduced risk of NMSC and AK while treatment lasted<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a>&nbsp;\t\t\t\t\t\t\n
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Resident's Forum
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
Autor para correspondencia
xavi_bosch92@hotmail.com

Corresponding author.
, D. Morgado-Carrasco, N. Martínez
Servicio de Dermatología, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Nonmelanoma skin cancer &#40;NMSC&#41; is the most common neoplasia in humans&#46; It includes basal cell carcinoma &#40;BCC&#41; and squamous cell carcinoma &#40;SCC&#41;&#46; Its main risk factors are accumulated exposure to sunlight&#44; immunosuppression&#44; and infection with the beta human papillomavirus&#46; The use of topical sunscreen is frequently indicated in secondary prevention&#46; In recent years&#44; new evidence supports the use of some drugs as chemoprophylactics &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">A randomized double-blind clinical trial in 932 high-risk patients &#40;98&#37; Caucasian males&#44; with a mean age of 71 years&#41; was recently published&#46; Chemoprevention was studied using a cycle of 5&#37; topical fluorouracil &#40;every 12<span class="elsevierStyleHsp" style=""></span>h for 4 weeks&#41; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>468&#41; versus placebo &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>464&#41; on the appearance of NMSC of the face and ears with surgical indication&#46; In the first year after treatment a lower number of SCC was detected &#40;1&#37; versus 4&#37;&#41; &#40;risk reduction of 75&#37; &#91;95&#37; CI&#44; 35&#37;&#8211;91&#37;&#93; &#91;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;002&#93;&#41;&#46; No differences were found in BCC &#40;10&#37; versus 11&#37;&#41;&#44; although the number of Mohs surgeries in the first year dropped&#46; After 4 years of follow-up&#44; no differences were found in the number of SCC or BCC between the 2 groups &#40;39&#37; versus 38&#37;&#41;&#46; In terms of adverse effects&#44; 92&#37; of the group receiving fluorouracil presented erythema &#40;21&#37; described it as severe&#41;&#44; but 85&#37; would use the treatment again if necessary&#46;<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&#46; It remains to be demonstrated whether an annual cycle of 5&#37; topical fluorouracil is an effective long-term strategy&#46; We must remember that 5-fluoracil is not sold in Spain and must be formulated&#46; This may limit its potential use in Spain&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Previously&#44; a phase-III randomized&#44; double-blind&#44; placebo-controlled clinical trial in 386 high-risk patients had demonstrated the efficacy of oral nicotinamide &#40;500<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h of vitamin B3&#41; as chemoprevention for NMSC&#46; In the 12 months that the nicotinamide was used&#44; the number of NMSC per person was reduced &#40;1&#46;8 versus 2&#46;4&#41;&#44; with a risk reduction of 23&#37; &#40;95&#37; CI&#44; 4&#37;&#8211;38&#37;&#41; &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;02&#41;&#44; and the drug was well tolerated&#46; This protective effect was lost 6 months after the treatment ended&#46;<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&#46; In a randomized&#44; placebo-controlled clinical trial &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2297&#41;&#44; the risk of SCC was lower among those who received 25&#44;000<span class="elsevierStyleHsp" style=""></span>IU&#47;d of retinol &#40;vitamin A&#41; &#40;hazard ratio&#44; 0&#46;74 &#91;95&#37; CI&#44; 0&#46;56&#8211;0&#46;99&#93; &#91;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;04&#93;&#41;&#46;<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&#44; but with greater toxicity&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">2&#44;4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Other oral drugs studied include capecitabin&#44; celecoxib&#44; and ibuprofen&#44; but greater evidence is required for their use to be recommended&#46; Most of the above-mentioned treatments have demonstrated efficacy in preventing SCC but not BCC&#46; This may be explained by their different etiologies&#44; including the fact that UV radiation damage and viral infection are not as important in BCC&#46; In terms of treatment of NMSC precursor lesions&#44; different topical agents have been shown to be effective&#44; such as ingenol mebutate&#44; imiquimod&#44; and diclofenac&#46; Photodynamic therapy is also highly effective in the treatment of these lesions&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">In solid-organ transplant and immunosuppressed patients&#44; it is important to reduce immunosuppression to the minimum effective dose and to replace calcineurin inhibitors &#40;cyclosporin and tacrolimus&#41; with mTOR inhibitors &#40;sirolimus or everolimus&#41;&#46; The use of sirolimus has been associated with a significant reduction in the risk of NMSC&#46;<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&#44; such as 5&#37; topical fluorouracil&#44; retinoids&#44; and oral nicotinamide to reduce this risk and the associated morbidity and mortality&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Bosch-Amate X&#44; Morgado-Carrasco D&#44; Mart&#237;nez N&#46; FR - Prevenci&#243;n farmacol&#243;gica del c&#225;ncer cut&#225;neo no-melanoma en pacientes de alto riesgo&#46; Actas Dermosifiliogr&#46; 2020&#59;111&#58;609&#8211;610&#46;</p>"
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          "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; SCC indicates squamous cell carcinoma&#59; NMSC&#44; nonmelanoma skin cancer&#59; RCT&#44; randomized clinical trial&#59; AK&#44; actinic keratosis&#46;</p>"
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                  \t\t\t\t">5-Fluorouracil&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Twice daily for 4 weeks &#40;an annual cycle&#63;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \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">25&#44;000<span class="elsevierStyleHsp" style=""></span>IU&#47;day for 5 years&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">30<span class="elsevierStyleHsp" style=""></span>mg&#47;day for 6 months&nbsp;\t\t\t\t\t\t\n
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