Scientific letter
Jaw osteonecrosis related to cabozantinib
Osteonecrosis mandibular en relación al empleo de cabozantinib
José Darío Sánchez López
, Juan Andrés Rodríguez Ruiz, Miguel Pérez de Perceval Tara
Corresponding author
Servicio de Cirugía Oral y Maxilofacial, Hospital Universitario Virgen de las Nieves de Granada, Granada, Spain
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In the last five years or so, we have seen the introduction of new antineoplastic agents that, unlike the traditional ones, act as monoclonal antibodies or tyrosine kinase (TK) inhibitors, which are involved in the development of ONJ, increasing the risk when used simultaneously with the former.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We report the case of a 56-year-old male patient with a history of metastatic clear cell renal cancer (mCRC) treated with cabozantinib at a dose of 140 mg/day orally, in the absence of treatment with both BPs and denosumab. Three years after this treatment, he was referred to our Unit for a 3-week history of pain, swelling and occasional suppuration at the left ramus of the jaw, and difficulty in chewing. The history-taking did not detect risk factors (smoking, type II diabetes) or precipitating factors (previous dental surgery), the clinical examination showed exposure of necrotic bone in the described position, approximately 3 cm in diameter, and the examination was completed by computerised axial tomography (CT), which showed findings compatible with ONJ. A biopsy of the lesion was taken for histopathological confirmation and treatment was started with amoxicillin 1 g/8 h for 15 days and thorough oral hygiene with 12% chlorhexidine rinses three times a day. The anatomical pathology analysis confirmed the suspected diagnosis of ONJ. After conservative treatment, there was a considerable decrease in symptomatology, with only intraoral exposure persisting after six months of follow-up, without pain or superinfection, but with persistent chewing discomfort. The causal relationship between ONJ and the administration of cabozantinib was established as a causal and compatible relationship applying the modified Karch and Lasagna causality algorithm, since ONJ occurred after the administration of said drug, and it could not be explained by the concomitant disease or other drugs or substances.</p><p id="par0015" class="elsevierStylePara elsevierViewall">CRC represents 75% of all renal cancers, caused by a VHL gene mutation. Most CRC have alterations in the von Hippel-Lindau protein, which induces higher levels of hepatocyte growth factor (MET) and epidermal growth factor 2 (VEGF-2), proteins that induce angiogenesis with the consequent increase in tumour growth and metastatic capacity.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Since 2012, cabozantinib has been the first-choice drug in the treatment of metastatic medullary thyroid cancer and third line in CRC; phase II clinical trials showed its activity against advanced prostate cancer. However, in preclinical models, cabozantinib showed multikinase inhibition capacity and inhibition of the MET and VEGF-2 receptors, showing its efficacy in reducing metastasis and drug resistance in these tumours, which led to its approval in 2016 for the treatment of patients with mCRC who did not respond to the first line of treatment (sunitinib and ponatinib) or who relapsed after treatment. Its use was expanded in December 2017 by the US Food and Drug Administration (FDA) as a first line treatment.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> The occurrence of ONJ would be closely linked to the triple inhibition mechanism on TK, MET and VEGF-2 receptors, inhibiting cell growth and angiogenesis. To date there is only one case reported by Marino et al.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> of ONJ after tooth extraction in a patient with metastatic thyroid cancer. Unlike the previous case, we report the first known case of extensive ONJ (E2 according to the latest 2014 classification) in a patient without risk factors or precipitating factors (dental extraction) linked to the use of cabozantinib in someone with metastatic mCRC after cessation of its administration three years earlier, in line with other published studies of antineoplastic agents with direct activity on VEGF (bevacizumab), which, although used in patients at risk, could act as precipitants of ONJ. However, due to the insufficient number of reported cases, there is a need for close monitoring and individualization of risks in the use of these drugs in the prevention of ONJ.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of interests</span><p id="par0020" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflict of interests" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Sánchez López JD, Rodríguez Ruiz JA, Pérez de Perceval Tara M. Osteonecrosis mandibular en relación al empleo de cabozantinib. Med Clin (Barc). 2021;156:627–628.</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" => "American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw—2014 update" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.L. Ruggiero" 1 => "T.B. Dodson" 2 => "J. Fantasia" 3 => "R. Goodway" 4 => "T. Aghaloo" 5 => "B. 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Walsh" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2016.70.7398" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2017" "volumen" => "35" "paginaInicial" => "591" "paginaFinal" => "597" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28199818" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Osteonecrosis of the jaw in a patient receiving cabozantinib" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "R. Marino" 1 => "F. Orlandi" 2 => "F. Arecco" 3 => "S. Gandolfo" 4 => "M. Pentenero" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/adj.12254" "Revista" => array:6 [ "tituloSerie" => "Aust Dent J" "fecha" => "2015" "volumen" => "60" "paginaInicial" => "528" "paginaFinal" => "531" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25474298" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000015600000012/v1_202106160926/S2387020621002436/v1_202106160926/en/main.assets" "Apartado" => array:4 [ "identificador" => "43311" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Scientific letters" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015600000012/v1_202106160926/S2387020621002436/v1_202106160926/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020621002436?idApp=UINPBA00004N" ]
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