Case Reports
Oral Acitretin and Topical Imiquimod as Neoadjuvant Treatment for Giant Basal Cell Carcinoma
Tratamiento neoadyuvante con acitretino oral e imiquimod tópico en el carcinoma basocelular gigante
V. Sanmartín
, R. Aguayo, M. Baradad, J.M. Casanova
Corresponding author
Departamento de Dermatología, Hospital Arnau de Vilanova, Lleida, Spain
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Dos carcinomas basocelulares gigantes erosionados localizados en la zona pectoral derecha. B. Las lesiones mostraron una mejoría significativa después de 4 meses de tratamiento con acitretino oral e imiquimod 5% crema. C. A los 6 meses el tamaño tumoral se había reducido en un 70%. D. Dos años después de la cirugía, sin signos de recidiva y con un resultado estético aceptable.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "V. Sanmartín, R. Aguayo, M. Baradad, J.M. Casanova" "autores" => array:4 [ 0 => array:2 [ "nombre" => "V." "apellidos" => "Sanmartín" ] 1 => array:2 [ "nombre" => "R." "apellidos" => "Aguayo" ] 2 => array:2 [ "nombre" => "M." "apellidos" => "Baradad" ] 3 => array:2 [ "nombre" => "J.M." 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Inflammatory, crusted plaque on the patient's scalp. Fungal culture was positive for <span class="elsevierStyleItalic">Trichophyton mentagrophytes</span>.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "L. Morell, M.J. Fuente, A. Boada, J.M. Carrascosa, C. Ferrándiz" "autores" => array:5 [ 0 => array:2 [ "nombre" => "L." "apellidos" => "Morell" ] 1 => array:2 [ "nombre" => "M.J." "apellidos" => "Fuente" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "Boada" ] 3 => array:2 [ "nombre" => "J.M." "apellidos" => "Carrascosa" ] 4 => array:2 [ "nombre" => "C." 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Sanmartín, R. Aguayo, M. Baradad, J.M. Casanova" "autores" => array:4 [ 0 => array:4 [ "nombre" => "V." "apellidos" => "Sanmartín" "email" => array:1 [ 0 => "vsanmartin6@yahoo.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "R." "apellidos" => "Aguayo" ] 2 => array:2 [ "nombre" => "M." "apellidos" => "Baradad" ] 3 => array:2 [ "nombre" => "J.M." "apellidos" => "Casanova" ] ] "afiliaciones" => array:1 [ 0 => array:1 [ "entidad" => "Departamento de Dermatología, Hospital Arnau de Vilanova, Lleida, Spain" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Tratamiento neoadyuvante con acitretino oral e imiquimod tópico en el carcinoma basocelular gigante" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1167 "Ancho" => 2668 "Tamanyo" => 411412 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A, Ulcerated giant basal cell carcinoma on the right cheek and temple. B, Impetiginous exudative erythematous tumor plaque after application of topical imiquimod 5% combined with oral acitretin for 1 month. C, Granulation tissue after 2 months of local radiotherapy. D, Permanent resolution of the tumor at 15 months of follow-up.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Basal cell carcinoma (BCC) is the most common tumor in humans. The incidence of this type of cancer in Spain is calculated to be 253 cases per 100 000 individuals per year.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The treatment with the highest cure rate is complete excision. However, depending on the size of the lesion and its location, this approach can be disfiguring and thus poorly accepted by the patient. The therapeutic options presented in such cases include electrosurgery, radiotherapy, topical imiquimod, 5-fluorouracil, and photodynamic therapy.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> We report on 2 patients with giant BCC who received a combination of oral acitretin and topical imiquimod as neoadjuvant treatment to reduce the size of the tumor.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Case Description</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Patient 1</span><p id="par0010" class="elsevierStylePara elsevierViewall">Our first patient was a 68-year-old woman with psoriasis since childhood for which she had received several topical treatments and UV-B phototherapy. She consulted in 2002 for a series of skin lesions that had developed gradually over the previous 10 years and that she felt were associated with her underlying skin condition. Nine of the lesions comprised erythematous desquamative plaques with pearly borders on the lower limbs and trunk. The lesions measured 1 to 4<span class="elsevierStyleHsp" style=""></span>cm in diameter, and some had small dots and globules of gray pigment Two ulcerated lesions were present on her chest; these also had pearly borders with pigmented areas and measured 11 x 18<span class="elsevierStyleHsp" style=""></span>cm and 4 x 8<span class="elsevierStyleHsp" style=""></span>cm (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A). Analysis of a punch biopsy specimen confirmed them as micronodular BCC. The patient was initially examined at the breast cancer unit, where she refused surgery owing to the potentially considerable damage arising from complete resection of the tumor. Her case was referred to the skin tumor board of our department, where we suggested reducing the size of the tumor using alternative treatment. We prescribed oral acitretin (25<span class="elsevierStyleHsp" style=""></span>mg/d) combined with daily topical imiquimod 5% cream. Flu-like symptoms appeared 2 months later; the dose of imiquimod was reduced to 3 alternate days per week, and her symptoms resolved. At 4 months, the smaller lesion had completely disappeared, and the larger lesion was reduced in size by 30% at 4 months (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B) and 70% at 6 months (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>C). Of note, analysis of biopsy specimens revealed recurrence of several of the tumors on the lower limbs, which were not treated with topical imiquimod. Even though treatment lasted 9 months, the size of the main tumor remained stable for the last 3 months. At this point, the residual tumor (5 x 7<span class="elsevierStyleHsp" style=""></span>cm) was treated with surgery. No recurrence of giant BCC has been detected after 8 years of follow-up (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>D).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Patient 2</span><p id="par0015" class="elsevierStylePara elsevierViewall">Our second patient was a 63-year-old man who consulted for an ulcerated tumor (10 x 7<span class="elsevierStyleHsp" style=""></span>cm) with pearly borders on the right cheek and temple. Histopathology confirmed the tumor to be infiltrative BCC. Given the size and location of the lesion, the skin tumor board rejected conventional approaches such as surgery and radiotherapy. The favorable outcome reported in the case described above led the board to recommend starting combination therapy with imiquimod 5% cream and oral acitretin (25<span class="elsevierStyleHsp" style=""></span>mg/d). Marked inflammation was evident 1 month later (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>B). After 15 weeks, the size of the tumor had been reduced to a maximum size of 3 x 4<span class="elsevierStyleHsp" style=""></span>cm. However, after 6 months, the tumor was seen to be progressing, possibly owing to a lack of adherence. As the patient refused surgery, we decided to initiate local radiotherapy (200 cGy administered in 30 doses) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>C). No recurrence of giant BCC has been detected after 2 years of follow-up (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>D).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0020" class="elsevierStylePara elsevierViewall">Radical resection is the most effective treatment for BCC. However, this approach can prove traumatic if the lesions are in functional areas or affect the patient's appearance.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> We found that the combination of oral retinoids and topical imiquimod was effective as neoadjuvant treatment to reduce the size of the tumor in 2 patients with giant BCC.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Retinoids are used in the primary prevention of nonmelanoma skin cancer in high-risk patients, such as transplant recipients, although they are also an option in the treatment of premalignant and malignant skin lesions. These agents regulate the cell cycle by acting on differentiation, inhibiting growth, and inducing apoptosis. In addition, they improve the cellular immune response and antagonize some well-known tumor promoters.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> We were able to find only 1 case of giant BCC (7<span class="elsevierStyleHsp" style=""></span>cm, multifocal) treated with oral retinoids in which the tumor remitted completely.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> However, the follow-up period in that study was very short.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Imiquimod is an immunomodulator that induces production of interferon (IFN) α by monocytes and dendritic cells. INF-α in turn interacts with type 1 helper T cells to induce release of INF-γ and interleukin 2. Thus, it functions as an antiviral agent and favors long-term immunologic memory against tumor cells.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,8</span></a> Imiquimod has proven effective in different studies on the treatment of nodular and superficial BCC, with cure rates ranging from 60% to 100%, depending on the regimen. The type and depth of the tumor affect the response to treatment, although the results of one prospective study indicate that the initial tumor area is the main predictor of remission.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Some cases of superficial giant BCC have resolved with topical imiquimod at different doses.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10,11</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Retinoids have been considered to have a synergistic effect when combined with imiquimod, IFN-α, or both. These effects are associated with more intense induction of specific genes stimulated by INF-α, including 2’-5’-oligoadenylate synthetase and protein kinase R. A study of pulmonary cancerous MCF-7 cells treated with a combination of retinoids and INF-α revealed overregulation of STAT1, an essential component of the signaling pathways of INF-α/β and INF-γ. Stimulation of this pathway could account for the effects of the combination of both agents on renal cancer cells, melanoma, and respiratory papillomatosis.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Other studies point to additive antineoplastic activity arising from the synergistic inhibition of angiogenesis.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13,14</span></a> To our knowledge, 2 patients with multiple BCCs (<2<span class="elsevierStyleHsp" style=""></span>cm) have been treated with this combination.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15,16</span></a> The first had xeroderma pigmentosum and the second had received Grenz ray therapy on the scalp as a child. Neither of the two was willing to undergo further surgery; therefore, both patients were prescribed oral acitretin and imiquimod 5% cream—the regimen was not described in the report—and the lesions resolved. Our review of the literature revealed no patients with giant BCC treated with this combination.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The combination of topical imiquimod 5% and oral retinoids to treat giant BCC did not completely resolve the tumor in our patients, although it did prove useful as neoadjuvant treatment by reducing the size of the tumor, thus enabling us to subsequently administer definitive treatment of the residual BCC. As the imiquimod regimen we prescribed was longer than recommended in the summary of product characteristics, symptoms and laboratory findings were closely monitored. The combination was adequately tolerated in both cases, and no notable adverse effects were recorded. It is worth noting that application of imiquimod to such a large ulcerated area induced systemic symptoms and resolved tumors at some distance from the treatment area. Furthermore, given that the tumor stabilized in both cases despite treatment, it would be important to establish whether some as yet unknown variable—histologic subtype, tumor area, or development of tolerance to imiquimod—could affect the response to therapy. The absence of a control group comprising patients treated with imiquimod only prevents us from knowing to what extent acitretin improved the results of therapy.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conclusion</span><p id="par0045" class="elsevierStylePara elsevierViewall">We believe that both of the cases we report illustrate a new therapeutic option in the neoadjuvant treatment of giant BCC, thus facilitating subsequent application of other definitive treatments. However, further studies are necessary to help us understand the synergistic or additive action of both drugs and their therapeutic potential.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflicts of Interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:2 [ "identificador" => "xres95656" "titulo" => "Abstract" ] 1 => array:2 [ "identificador" => "xpalclavsec82816" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres95657" "titulo" => "Resumen" ] 3 => array:2 [ "identificador" => "xpalclavsec82815" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Case Description" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Patient 1" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Patient 2" ] ] ] 6 => array:2 [ "identificador" => "sec0025" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0030" "titulo" => "Conclusion" ] 8 => array:2 [ "identificador" => "sec0035" "titulo" => "Conflicts of Interest" ] 9 => array:2 [ "identificador" => "xack35209" "titulo" => "Acknowledgements" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec82816" "palabras" => array:4 [ 0 => "Giant basal cell carcinoma" 1 => "Acitretin" 2 => "Imiquimod" 3 => "Interferon-α" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec82815" "palabras" => array:4 [ 0 => "Carcinoma basocelular gigante" 1 => "Acitretino" 2 => "Imiquimod" 3 => "Interferón-α" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Giant basal cell carcinoma (BCC) is defined as a tumor with a diameter of 5<span class="elsevierStyleHsp" style=""></span>cm or more. Surgery, the treatment of choice for any type of BCC, can cause considerable anatomical damage in large tumors. In 2 patients with giant BCC we therefore provided neoadjuvant treatment with a combination of oral acitretin and topical 5% imiquimod. Acitretin is a systemic retinoid used for primary prevention of nonmelanoma skin cancer. Imiquimod is an immunomodulator whose approved indications include treatment of nonfacial superficial BCC less than 2<span class="elsevierStyleHsp" style=""></span>cm in diameter. Previous studies have demonstrated a synergic anticancer effect of both drugs in vitro and in vivo. This combination produced a marked reduction in tumor mass in our patients. Later we were able to provide definitive treatment, which achieved complete remission of the tumors.</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">El carcinoma basocelular (CBC) gigante se define como aquel que mide 5<span class="elsevierStyleHsp" style=""></span>cm o más. Aunque la cirugía se considera el tratamiento de elección para cualquier tipo de CBC, en los de gran tamaño, puede ser altamente destructiva. Así, utilizamos la combinación de acitretino oral e imiquimod 5% tópico como tratamiento neoadyuvante en dos pacientes afectos de un CBC gigante. El acitretino es un retinoide sistémico que se utiliza en la prevención primaria del cáncer cutáneo no melanoma. El imiquimod es un inmunomodulador aprobado para el tratamiento, entre otros, de CBC superficiales no faciales menores de 2<span class="elsevierStyleHsp" style=""></span>cm. Estudios previos han demostrado una acción sinérgica anticarcinogénica de ambos fármacos, tanto <span class="elsevierStyleItalic">in vivo</span> como <span class="elsevierStyleItalic">in vitro</span>. Dicha combinación produjo en nuestros pacientes una gran reducción de la masa tumoral, lo que nos permitió aplicar posteriormente un tratamiento definitivo con la remisión completa de los CBC.</p>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara">Please cite this article as: Sanmartín V, et al. Tratamiento neoadyuvante oral e imiquimod tópico en el carcinoma basocelular gigante. Actas Dermosifiliogr. 2012;103:149-152.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2072 "Ancho" => 2275 "Tamanyo" => 428856 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A, Two eroded giant basal cell carcinomas on the right side of the chest. B, Significant improvement in the lesions after 4 months of treatment with oral acitretin and imiquimod 5% cream. C, Reduction in the size of the tumor (70%) after 6 months. D, No signs of recurrence and acceptable cosmetic outcome 2 years after surgery.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1167 "Ancho" => 2668 "Tamanyo" => 411412 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A, Ulcerated giant basal cell carcinoma on the right cheek and temple. B, Impetiginous exudative erythematous tumor plaque after application of topical imiquimod 5% combined with oral acitretin for 1 month. C, Granulation tissue after 2 months of local radiotherapy. 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| Year/Month | Html | Total | |
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| 2016 October | 257 | 23 | 280 |
| 2016 September | 180 | 12 | 192 |
| 2016 August | 194 | 18 | 212 |
| 2016 July | 145 | 18 | 163 |
| 2016 June | 11 | 9 | 20 |
| 2016 May | 13 | 12 | 25 |
| 2016 April | 6 | 6 | 12 |
| 2016 March | 13 | 3 | 16 |
| 2016 February | 8 | 6 | 14 |
| 2016 January | 13 | 9 | 22 |
| 2015 December | 11 | 11 | 22 |
| 2015 November | 9 | 1 | 10 |
| 2015 October | 14 | 4 | 18 |
| 2015 September | 4 | 3 | 7 |
| 2015 August | 14 | 5 | 19 |
| 2015 July | 183 | 11 | 194 |
| 2015 June | 79 | 10 | 89 |
| 2015 May | 108 | 12 | 120 |
| 2015 April | 113 | 15 | 128 |
| 2015 March | 97 | 16 | 113 |
| 2015 February | 96 | 8 | 104 |
| 2015 January | 74 | 16 | 90 |
| 2014 December | 89 | 10 | 99 |
| 2014 November | 67 | 16 | 83 |
| 2014 October | 82 | 12 | 94 |
| 2014 September | 62 | 15 | 77 |
| 2014 August | 95 | 17 | 112 |
| 2014 July | 90 | 17 | 107 |
| 2014 June | 96 | 18 | 114 |
| 2014 May | 76 | 14 | 90 |
| 2014 April | 55 | 12 | 67 |
| 2014 March | 62 | 25 | 87 |
| 2014 February | 24 | 8 | 32 |
| 2014 January | 21 | 7 | 28 |
| 2013 December | 42 | 13 | 55 |
| 2013 November | 18 | 13 | 31 |
| 2013 October | 18 | 15 | 33 |
| 2013 September | 12 | 10 | 22 |
| 2013 August | 7 | 22 | 29 |
| 2013 July | 7 | 22 | 29 |
| 2013 June | 7 | 31 | 38 |
| 2013 May | 9 | 9 | 18 |
| 2013 April | 13 | 13 | 26 |
| 2013 March | 18 | 4 | 22 |
| 2013 February | 34 | 3 | 37 |
| 2013 January | 56 | 4 | 60 |
| 2012 December | 23 | 7 | 30 |
| 2012 November | 1 | 2 | 3 |
| 2012 October | 1 | 1 | 2 |
Show all
