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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Apalutamide is an androgen receptor signaling inhibitor &#40;ARSi&#41;&#44; indicated as standard of care in 2019 in the treatment of metastatic castration-sensitive prostate cancer &#40;mCSPC&#41; together with androgen deprivation therapy &#40;ADT&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> The incidence of interstitial lung disease &#40;ILD&#41; associated with apalutamide is very uncommon with few cases of this side effect reported on the literature&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">2&#8211;4</span></a> ILD can become serious so clinicians should be alerted to this potential adverse effect and know the clinical management in this situation&#46; Here&#44; we present two cases of apalutamide-induced interstitial lung disease who were successfully treated with high-dose corticosteroids&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The first case refers to a 55-year-old man without medical history of interest diagnosed of metachronous low volume mCSPC&#46; He initiated Triptorelin 22&#46;5<span class="elsevierStyleHsp" style=""></span>mg and a month later initiated apalutamide&#46; The dose of apalutamide was reduced from 240<span class="elsevierStyleHsp" style=""></span>mg to 180<span class="elsevierStyleHsp" style=""></span>mg per day after two months due to the appearance of grade III skin rash&#46; One month later&#44; the patient experienced cough and progressive respiratory distress&#46; On auscultation&#44; fine crackles were heard in both lungs&#46; Chest CT showed subpleural parenchymal bands&#44; ground-glass opacities and bilateral consolidations &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#41;&#44; without alterations in previous imaging test&#46; Based on these findings and on the absence of any other suspected drug&#44; the diagnosis of apalutamide-induced ILD was made&#44; so apalutamide was discontinued and endovenous metilprednisolone 1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day was started&#46; After five days&#44; the treatment was switched to oral deflazacort 80<span class="elsevierStyleHsp" style=""></span>mg&#47;day for seven days&#44; progressively reducing 20<span class="elsevierStyleHsp" style=""></span>mg per week until discontinued&#46; The patient improved his respiratory status after 15 days of corticosteroids treatment&#46; Chest-CT at 3 months after discontinuing apalutamide&#44; showed a significant improvement with resolution of previously described pulmonary signs &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The second case refers to a 73-year-old man without medical history of interest diagnosed &#8220;de novo&#8221; mCSPC and treated with radiotherapy to the prostate as well as leuprorelin 45<span class="elsevierStyleHsp" style=""></span>mg and apalutamide &#40;240<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&#46; Six months after initiation of apalutamide he described an evolution of two months of cough&#44; mucous expectoration and weight loss&#44; the patient was admitted to pneumology due to clinical worsening and acute respiratory failure&#46; Chest-CT showed bilateral patchy areas of ground-glass opacities with bronchiectasis &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>A&#41;&#44; without alterations in previous imaging test&#46; Bronchoscopy with cytology only appeared inflammatory cellularity &#40;9&#37; granulocytic polynuclears&#44; 1&#37; eosinophils&#44; 5&#37; monocytes&#44; 27&#37; alveolar macrophages&#44; 52&#37; lymphocytes with CD4&#47;CD8 ratio of 0&#46;25&#41;&#46; Infectious etiology was ruled out through PCR&#44; blood cultures and BAS citology&#46; He was diagnosed of apalutamide-induced ILD&#44; so he started endovenous metilprednisolone 1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day and switched to oral prednisone 60<span class="elsevierStyleHsp" style=""></span>mg&#47;day for fifteen days&#44; progressively reducing 7&#46;5<span class="elsevierStyleHsp" style=""></span>mg per week until discontinued with rapid resolution of the dyspnea&#46; CT reassessment two months after showed practical resolution of the pulmonary signs &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>B&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Currently both patients are undergoing follow-up observation with ADT treatment without progression and no respiratory symptoms&#46; Apalutamide was no re-administered in both cases&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Drug-induced ILD is a serious condition that occurs in 3&#8211;5&#37; of all cases of ILD ad it is associated with antineoplastic drugs like bleomycin&#44; targeted drugs&#44; immune checkpoint inhibitors or antiandrogens &#40;bicalutamide&#44; flutamide&#44; goserelin&#44; degarelix and apalutamide&#41; in which it tends to occur during first year after starting treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">4&#44;5</span></a> In our cases&#44; it manifested at 3 and 6 months respectively&#46; Although cases of ILD have been described in the literature with gonadotropin releasing hormone agonist&#44;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> in our reported cases we did not find a causal relationship with ILD since the patients continued treatment with ADT without recurrence of symptoms and with radiological improvement&#46; The occurrence of ILD due to apalutamide has been described in adverse effects databases&#44;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">4&#44;5</span></a> but there are only a few cases reported in Asian patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">2&#44;3</span></a> To the best of our knowledge these are the first two cases of apalutamide-induced ILD reported in European patients&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">In conclusion&#44; apalutamide-induced ILD is a rare side effect that must keep in mind due to its potential severity&#44; so lung function should be monitored in patients treated with ARSi&#44; especially during first year of therapy&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Authors&#8217; contributions</span><p id="par0035" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Roc&#237;o del Castillo-Acu&#241;a</span>&#58; Writing-review &#38; editing&#46; <span class="elsevierStyleBold">Ana Serradilla</span>&#58; Writing-review &#38; editing&#46; <span class="elsevierStyleBold">Fernando L&#243;pez-Campos</span>&#58; Writing-review &#38; editing&#46; Supervision&#46; <span class="elsevierStyleBold">Felipe Cou&#241;ago</span>&#58; Writing-review &#38; editing&#46; Supervision&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflict of interests</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors state that they have no conflict of interests&#46;</p></span></span>"
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Journal Information
Vol. 60. Issue 8.
Pages 537-538 (August 2024)
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Vol. 60. Issue 8.
Pages 537-538 (August 2024)
Clinical Letter
Interstitial Lung Disease Caused by Apalutamide for Metastatic Castration-Sensitive Prostate Cancer
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Rocío del Castillo-Acuñaa,
Corresponding author
rociodelcas@yahoo.es

Corresponding author.
, Ana Serradillab, Fernando López-Camposc, Felipe Couñagod,e,f
a Department of Radiation Oncology, Hospital Universitario Punta de Europa, Algeciras, Spain
b Department of Radiation Oncology, Complejo Hospitalario de Jaen, Jaen, Spain
c Department of Radiation Oncology, Hospital Universitario Ramón y Cajal, Madrid, Spain
d Department of Radiation Oncology GenesisCare, Hospital San Francisco de Asís, Madrid, Spain
e Department of Radiation Oncology GenesisCare, Hospital Vithas La Milagrosa, Madrid, Spain
f Director Nacional Clínico y de Investigación, GenesisCare España, Madrid, Spain
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