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(B) Hyperinflating lytic lesion in the D7 vertebra, with partial infiltration of its posterior elements and edema of the adjacent prevertebral soft tissues. (C) Soft tissue biopsy (×20): multinucleated giant cells (red arrows) loosely distributed along with numerous mononuclear cells in a fibrous background (×20 magnification). (D) Bronchial mucosa (×10): atypical cell proliferation located at the level of the submucosa composed of soft-looking mononuclear cells, multinucleated giant cells (red arrow) and formation of metaplastic bone tissue (red arrow).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Eduardo Solís García, Blanca de Vega Sánchez, Pablo Panadero Meseguer" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Eduardo" "apellidos" => "Solís García" ] 1 => array:2 [ "nombre" => "Blanca" "apellidos" => "de Vega Sánchez" ] 2 => array:2 [ "nombre" => "Pablo" "apellidos" => "Panadero Meseguer" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289622004392?idApp=UINPBA00003Z" "url" => "/03002896/0000005800000010/v2_202302271800/S0300289622004392/v2_202302271800/en/main.assets" ] "en" => array:15 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Director</span>" "titulo" => "Why Use Aprepitant Only as a Cough Suppressant in Lung Cancer When at Higher Doses it Could Also Exert an Antitumor Action?" "tieneTextoCompleto" => true "saludo" => "To the Director," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "727" "paginaFinal" => "728" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Miguel Muñoz, Miguel E. Muñoz, Ferran Morell, Rafael Coveñas" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Miguel" "apellidos" => "Muñoz" "email" => array:1 [ 0 => "mmunoz@cica.es" ] "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">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Miguel E." "apellidos" => "Muñoz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 2 => array:3 [ "nombre" => "Ferran" "apellidos" => "Morell" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 3 => array:3 [ "nombre" => "Rafael" "apellidos" => "Coveñas" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">f</span>" "identificador" => "aff0030" ] ] ] ] "afiliaciones" => array:6 [ 0 => array:3 [ "entidad" => "Research Laboratory on Neuropeptides, Institute of Biomedicine of Seville (IBIS), Seville, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Pediatric Intensive Care United, Virgen del Rocío University Hospital, Seville, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Health Emergency Center 061, Seville, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Vall d’hebron Institut de Recerca (VHIR), Pulmonology Department, Ciberes, Barcelona, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Institute of Neurosciences of Castilla y León (INCYL), Laboratory of Neuroanatomy of the Peptidergic Systems, University of Salamanca, Salamanca, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Group GIR-USAL: BMD (Bases Moleculares del Desarrollo), Salamanca, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1621 "Ancho" => 2508 "Tamanyo" => 282999 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Lung cancer (LC) patients: substance P (SP), via the neurokinin-1 receptor (NK-1R), promotes cough and tumor progression. The NK-1R antagonist aprepitant could exert a dual therapeutic effect in these patients: cough suppressant and antitumor action.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Effective antitussive cough treatments are an important need in patients with lung cancer (LC). Aprepitant drug, a selective neurokinin-1 receptor (NK-1R) antagonist and used for the treatment of nausea/vomiting, blocks the activation of the receptor by substance P (SP); this activation also mediates cough.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> Two randomized trials have clearly shown that aprepitant (day 1: 125<span class="elsevierStyleHsp" style=""></span>mg; 2−7/2−3: 80<span class="elsevierStyleHsp" style=""></span>mg) suppresses cough in LC patients.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1,2</span></a> Preclinical/clinical studies have also shown the involvement of the SP/NK-1R system in cancer progression and the potential use of aprepitant as a new antitumor drug has been suggested.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> The key-points of these studies are the following: LC cells synthesize/release SP which acts through autocrine, paracrine and neuroendocrine (tumor mass) mechanisms; LC tumor mass increases SP level in lung and blood; compared to healthy subjects, SP plasma levels are higher in subjects with cough and in patients with cancer; SP increases both cough and the proliferation of LC cells; LC cells overexpress the NK-1R; this receptor is involved in the viability of these cells; in a concentration-dependent manner, NK-1R antagonists (including aprepitant) suppress cough and exert an antitumor action because they decrease LC cell proliferation and induce the death of LC cells by apoptosis.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> NK-1R antagonists also inhibit the migration of tumor cells (counteracting invasion/metastasis) and angiogenesis. Aprepitant crosses the blood-brain barrier and could be useful to treat LC metastasis.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> For the first time, a combination therapy using aprepitant (1140<span class="elsevierStyleHsp" style=""></span>mg/day for 45 days; compassionate use) and palliative radiotherapy to treat a patient suffering from LC has been reported<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a>: the tumor mass (8<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>7<span class="elsevierStyleHsp" style=""></span>cm) disappeared six months after treatment and no severe side-effect was found. The patient showed a general good health with weight gain and no biochemical analytical alteration.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> Before surgery, radiotherapy is currently used to partially decrease the size of large tumors. Thus, it seems that the whole disappearance of the LC tumor mass was due to the combination therapy of radiotherapy and aprepitant, although this must be confirmed in future studies.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> Importantly, the antitumor action of aprepitant is against any type of LC cells (small and non-small LC cells) because these cells overexpress the NK-1R.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> It has been suggested that the clinical antitumor dose of aprepitant to be administered could be 20−40<span class="elsevierStyleHsp" style=""></span>mg/kg/day.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> In humans, the safety of aprepitant (300<span class="elsevierStyleHsp" style=""></span>mg/day for 45 days; 375<span class="elsevierStyleHsp" style=""></span>mg/day for two weeks) was excellent and it was well tolerated.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> Accordingly, an important question arises: Why use aprepitant only as a cough suppressant in LC when at higher doses it could also exert an antitumor action against LC? (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) Thus, in LC patients: (1) aprepitant, in a concentration-dependent manner, could exert a dual therapeutic effect: cough suppressant and antitumor action against LC; (2) aprepitant must be repurposed as an antitumor drug, alone or in combination therapy, and (3) phase I and II clinical trials are urgently needed to assess its safety/efficacy. What are we waiting for when it could just be a question of dosage?</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0010" class="elsevierStylePara elsevierViewall">Not declared.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Author's contributions</span><p id="par0015" class="elsevierStylePara elsevierViewall">All authors participated equally.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflict of interest</span><p id="par0020" class="elsevierStylePara elsevierViewall">Not declared.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Funding" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Author's contributions" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflict of interest" ] 3 => array:2 [ "identificador" => "xack653545" "titulo" => "Acknowledgments" ] 4 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1621 "Ancho" => 2508 "Tamanyo" => 282999 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Lung cancer (LC) patients: substance P (SP), via the neurokinin-1 receptor (NK-1R), promotes cough and tumor progression. The NK-1R antagonist aprepitant could exert a dual therapeutic effect in these patients: cough suppressant and antitumor action.</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" => "Aprepitant for cough in lung cancer. A randomized placebo-controlled trial and mechanistic insights" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.A. Smith" 1 => "A. Harle" 2 => "R. Dockry" 3 => "K. Holt" 4 => "P. Russell" 5 => "A. Molassiotis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/rccm.202006-2359OC" "Revista" => array:5 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2021" "volumen" => "203" "paginaInicial" => "737" "paginaFinal" => "745" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Aprepitant for cough suppression in advanced lung cancer: a randomized trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "V. Noronha" 1 => "A. Bhattacharjee" 2 => "V.M. Patil" 3 => "A. Joshi" 4 => "N. Menon" 5 => "S. 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Coveñas" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3390/cancers12092682" "Revista" => array:5 [ "tituloSerie" => "Cancers (Basel)" "fecha" => "2020" "volumen" => "12" "paginaInicial" => "2682" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32962202" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0045" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The substance P/neurokinin-1 receptor system in lung cancer: focus on the antitumor action of neurokinin-1 receptor antagonists" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Muñoz" 1 => "A. González-Ortega" 2 => "M. Rosso" 3 => "M.J. Robles-Frias" 4 => "A. Carranza" 5 => "M.V. Salinas-Martín" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.peptides.2012.09.024" "Revista" => array:6 [ "tituloSerie" => "Peptides" "fecha" => "2012" "volumen" => "38" "paginaInicial" => "318" "paginaFinal" => "325" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23026680" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Neurokinin-1 receptor antagonist aprepitant and radiotherapy, a successful combination therapy in a patient with lung cancer: a case report" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M. Muñoz" 1 => "J.C. Crespo" 2 => "J.P. Crespo" 3 => "R. Coveñas" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3892/mco.2019.1857" "Revista" => array:6 [ "tituloSerie" => "Mol Clin Oncol" "fecha" => "2019" "volumen" => "11" "paginaInicial" => "50" "paginaFinal" => "54" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31289677" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack653545" "titulo" => "Acknowledgments" "texto" => "<p id="par0025" class="elsevierStylePara elsevierViewall">We would like to thank Mr. Javier Muñoz (Seville University) for technical assistance.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/03002896/0000005800000010/v2_202302271800/S0300289622003398/v2_202302271800/en/main.assets" "Apartado" => array:4 [ "identificador" => "94562" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Letters to the Director" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/03002896/0000005800000010/v2_202302271800/S0300289622003398/v2_202302271800/en/main.pdf?idApp=UINPBA00003Z&text.app=https://archbronconeumol.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289622003398?idApp=UINPBA00003Z" ]
Journal Information
Letter to the Director
Why Use Aprepitant Only as a Cough Suppressant in Lung Cancer When at Higher Doses it Could Also Exert an Antitumor Action?
a Research Laboratory on Neuropeptides, Institute of Biomedicine of Seville (IBIS), Seville, Spain
b Pediatric Intensive Care United, Virgen del Rocío University Hospital, Seville, Spain
c Health Emergency Center 061, Seville, Spain
d Vall d’hebron Institut de Recerca (VHIR), Pulmonology Department, Ciberes, Barcelona, Spain
e Institute of Neurosciences of Castilla y León (INCYL), Laboratory of Neuroanatomy of the Peptidergic Systems, University of Salamanca, Salamanca, Spain
f Group GIR-USAL: BMD (Bases Moleculares del Desarrollo), Salamanca, Spain