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LC cells synthesize&#47;release SP which acts through autocrine&#44; paracrine and neuroendocrine &#40;tumor mass&#41; mechanisms&#59; LC tumor mass increases SP level in lung and blood&#59; compared to healthy subjects&#44; SP plasma levels are higher in subjects with cough and in patients with cancer&#59; SP increases both cough and the proliferation of LC cells&#59; LC cells overexpress the NK-1R&#59; this receptor is involved in the viability of these cells&#59; in a concentration-dependent manner&#44; NK-1R antagonists &#40;including aprepitant&#41; suppress cough and exert an antitumor action because they decrease LC cell proliferation and induce the death of LC cells by apoptosis&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> NK-1R antagonists also inhibit the migration of tumor cells &#40;counteracting invasion&#47;metastasis&#41; and angiogenesis&#46; Aprepitant crosses the blood-brain barrier and could be useful to treat LC metastasis&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> For the first time&#44; a combination therapy using aprepitant &#40;1140<span class="elsevierStyleHsp" style=""></span>mg&#47;day for 45 days&#59; compassionate use&#41; and palliative radiotherapy to treat a patient suffering from LC has been reported<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a>&#58; the tumor mass &#40;8<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>7<span class="elsevierStyleHsp" style=""></span>cm&#41; disappeared six months after treatment and no severe side-effect was found&#46; The patient showed a general good health with weight gain and no biochemical analytical alteration&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> Before surgery&#44; radiotherapy is currently used to partially decrease the size of large tumors&#46; Thus&#44; it seems that the whole disappearance of the LC tumor mass was due to the combination therapy of radiotherapy and aprepitant&#44; although this must be confirmed in future studies&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> Importantly&#44; the antitumor action of aprepitant is against any type of LC cells &#40;small and non-small LC cells&#41; because these cells overexpress the NK-1R&#46;<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&#8722;40<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> In humans&#44; the safety of aprepitant &#40;300<span class="elsevierStyleHsp" style=""></span>mg&#47;day for 45 days&#59; 375<span class="elsevierStyleHsp" style=""></span>mg&#47;day for two weeks&#41; was excellent and it was well tolerated&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> Accordingly&#44; an important question arises&#58; Why use aprepitant only as a cough suppressant in LC when at higher doses it could also exert an antitumor action against LC&#63; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41; Thus&#44; in LC patients&#58; &#40;1&#41; aprepitant&#44; in a concentration-dependent manner&#44; could exert a dual therapeutic effect&#58; cough suppressant and antitumor action against LC&#59; &#40;2&#41; aprepitant must be repurposed as an antitumor drug&#44; alone or in combination therapy&#44; and &#40;3&#41; phase I and II clinical trials are urgently needed to assess its safety&#47;efficacy&#46; What are we waiting for when it could just be a question of dosage&#63;</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&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Author&#39;s contributions</span><p id="par0015" class="elsevierStylePara elsevierViewall">All authors participated equally&#46;</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&#46;</p></span></span>"
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                      "titulo" => "Neurokinin-1 receptor antagonist aprepitant and radiotherapy&#44; a successful combination therapy in a patient with lung cancer&#58; a case report"
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        "texto" => "<p id="par0025" class="elsevierStylePara elsevierViewall">We would like to thank Mr&#46; Javier Mu&#241;oz &#40;Seville University&#41; for technical assistance&#46;</p>"
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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?
Miguel Muñoza,b,
Corresponding author
mmunoz@cica.es

Corresponding author.
, Miguel E. Muñozc, Ferran Morelld, Rafael Coveñase,f
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

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