Letter to the Editor
Capillary and cutaneous hypopigmentation secondary to pazopanib
Hipopigmentación capilar y cutánea secundaria a pazopanib
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hypopigmentation secondary to pazopanib" "tieneTextoCompleto" => true "saludo" => "Dear Editor:" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "246" "paginaFinal" => "247" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Marina Meri-Abad, Ana Blasco Cordellat, Carlos Camps Herrero" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Marina" "apellidos" => "Meri-Abad" "email" => array:1 [ 0 => "Marinameri@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Ana" "apellidos" => "Blasco Cordellat" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Carlos" "apellidos" => "Camps Herrero" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Oncología Médica, Consorcio Hospital General Universitario Valencia, Valencia, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "CIBERONC, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Departamento de Medicina, Universidad de Valencia, Valencia, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Hipopigmentación capilar y cutánea secundaria a pazopanib" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 694 "Ancho" => 1255 "Tamanyo" => 109346 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Patient before and after experiencing rapid-onset capillary and cutaneous hypopigmentation induced by treatment with pazopanib.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Pazopanib is a multi-targeted tyrosine kinase inhibitor (TKI) whose effectiveness has been proven in certain types of soft-tissue sarcoma (STS) following progression to chemotherapy. Changes in skin pigmentation have been described as one of its infrequent adverse effects. In this paper we describe the case of a patient with metastatic STS who developed rapid-onset capillary and cutaneous hypopigmentation.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The case corresponded to a 65-year-old man diagnosed with metastatic (pulmonary metastases), high-grade, non-specific, soft-tissue sarcoma in his right thigh, for which he started treatment with pazopanib 800 mg/day in March 2020, following progression to chemotherapy. After completing the first cycle of this treatment, he developed grade-3 digestive toxicity, owing to which the treatment dose had to be reduced to 600 mg/day, resulting in a gradual improvement. However, he subsequently developed a picture of grade-1 capillary and cutaneous hypopigmentation that persisted throughout the entire treatment duration (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). He did not receive specific treatment and reported no worsening in his quality of life in relation to this symptom. Because the first follow-up evaluation revealed stability of the disease, he continued to receive treatment with pazopanib. In December 2020, after completing ten cycles of this treatment, a follow-up evaluation revealed evidence of pulmonary progression of the disease, owing to which the drug was finally discontinued. His capillary and cutaneous hypopigmentation persisted at the last follow-up visit.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Pazopanib is a TKI that inhibits the vascular endothelial growth factor, the platelet growth factor, and the c-kit stem cell factor (SCF) receptor.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The efficacy of pazopanib in patients with metastatic non-adipocytic STS was evaluated in the PALETTE study.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> In said study, the most frequent adverse effects associated with pazopanib were fatigue, diarrhea, nausea, weight loss, and hypertension. Although 38% of the patients who were inclued in the study exhibited any degree of skin pigmentation changes, no case reports describing this effect in sarcoma patients have been found in the literature. In fact, we performed a literature search in PubMed using descriptors “hypopigmentation”, “pazopanib”, and “sarcoma” between 2012 and the present, with no records being retreived with this combination of keywords.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Capillary pigmentation is regulated by several factors, including SCF and its c-kit TKI, and it has been reported that mutations in these genes can result in depigmentation.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Treatment with TKIs might cause such depigmentation by inhibiting c-kit, although the exact pathophysiological mechanism of this phenomenon has not yet been clarified. Pharmacovigilance studies on TKIs have reported a 35% incidence of hair color changes, although it is suspected that this figure might be an understimation. Cases of changes in hair and skin coloration in patients treated with pazopanib for renal cell carcinoma and thyroid cancer have been described in the literature.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a> In said cases, the patients exhibited a regression of their disease with the treatment; however, since these were clinical case reports, it cannot be hypothesized whether such phenomenon could be a predictor of response to the therapy. As in our case, these patients developed the hypopigmentation during the first treatment cycles. No specific treatment for this phenomenon nor a need to discontinue the treatment following the onset of this symptom have been described in the literature, although it has been stated that it can cause psychological stress, as the patients self-perceive it as a sign of alarm. Therefore, they must know that there is a chance of developing this symptom in order to ensure adequate counseling prior to starting the treatment.</p><p id="par0025" class="elsevierStylePara elsevierViewall">To our knowledge, this is the first reported case of rapid-onset capillary and cutaneous hypopigmentation in a patient with sarcoma treated with pazopanib. Although we believe it could have been secondary to c-kit inhibition by the multikinase inhibitors, the actual underlying pathophysiological mechanism remains unknown. Hence, this case highlights the importance of clinicians to be mindful of this side effect in order to minimize their patients’ psychosocial stress and imparied quality of life as the use of targeted therapies in oncology increases. In case of developing this symptom, patients should be counseled on appropriate sun protection measures, as they may be at an increased risk of experiencing photosensitivity disorders.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Meri-Abad M, Blasco Cordellat A, Camps Herrero C. Hipopigmentación capilar y cutánea secundaria a pazopanib. Med Clin (Barc). 2022;158:246–247.</p>" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 694 "Ancho" => 1255 "Tamanyo" => 109346 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Patient before and after experiencing rapid-onset capillary and cutaneous hypopigmentation induced by treatment with pazopanib.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pazopanib: clinical development of a potent anti-angiogenic drug" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "F.A.B. 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Tečić Vuger" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/bcr-2018-224209" "Revista" => array:4 [ "tituloSerie" => "BMJ Case Rep" "fecha" => "2018" "paginaInicial" => "1" "paginaFinal" => "4" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of pazopanib on hair and skin hypopigmentation: a series of three patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "K. Sideras" 1 => "M.E. Menefee" 2 => "J.K. Burton" 3 => "S.P. Ivy" 4 => "C. Erlichman" 5 => "K.C. Bible" ] ] ] ] ] "host" => array:2 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2010" "volumen" => "28 15 Suppl" "paginaInicial" => "13602" ] ] 1 => array:1 [ "WWW" => array:1 [ "link" => "https://doi.org/10.1200/jco.2010.28.15_suppl.e13602" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000015800000005/v1_202203050916/S2387020622000626/v1_202203050916/en/main.assets" "Apartado" => array:4 [ "identificador" => "43309" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015800000005/v1_202203050916/S2387020622000626/v1_202203050916/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020622000626?idApp=UINPBA00004N" ]
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