Cabozantinib as the causative agent of high-grade fever in a patient with a background of metastatic clear cell renal ce
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CASE REPORT
Cabozantinib as the causative agent of high‑grade fever in a patient with a background of metastatic clear cell renal cell carcinoma: a case report H. M. N. Chen1, M. Morris1 and P. M. Manders1,2*
Abstract Background: Fever, as an adverse event, is well documented in a wide array of drugs including multiple tyrosine kinase inhibitors however, it is not a previously well described consequence of the novel multi-targeted tyrosine kinase inhibitor, cabozantinib. Case presentation: In this paper we document the first detailed review of high-grade fevers in a 54 year old male (Caucasian) with a background of metastatic clear cell renal cell carcinoma recently commenced on cabozantinib. After detailed investigation, we exclude infection and other common causes of fever as the causative agent and further, definitively resolve the recurrent fever by ceasing cabozantinib and starting a short course of oral corticosteroids. Conclusions: We have demonstrated that cabozantinib should always be considered in the aetiology of high-grade fever in relevant patients. Further, we demonstrate that temporary cessation of cabozantinib and a course of shortterm steroids can induce resolution of fever and allow for recommencement of cabozantinib safely thereafter. Keywords: Cabozantinib, Renal, Fever, Case report Introduction Treatment of metastatic renal cell carcinoma (mRCC) is rapidly evolving with the introduction of new targeted therapies and ongoing investigation into combination therapies using immunotherapy backbones [1]. Vascular endothelial growth factor (VEGF) is a potent angiogenic stimulus supporting the growth of renal cell carcinoma (RCC) [2]. VEGF and associated downstream activation pathways, therefore provide a number of targets for metastatic growth inhibition [3]. Cabozantinib is an oral, small molecule, multi-targeted tyrosine kinase inhibitor (TKI) with proven activity against VEGF-Receptor (VEGFR) mediated cell cycling *Correspondence: [email protected] 1 Sunshine Coast University Hospital, 6 Doherty St, Birtinya 4575, Australia Full list of author information is available at the end of the article
activation. In addition, it also inhibits both the MET and AXL tyrosine kinase pathways which have been shown to associate with poorer prognosis due to conferral of resistance to VEGFR-specific inhibition [4]. Common adverse effects of cabozantinib are similar to those typically found in earlier VEGF-specific TKI’s. These include fatigue, diarrhoea, hypertension, palmarplantar erythrodysesthesia, anorexia and dysgeusia [4, 5]. To our knowledge, high grade fever with rigors in the absence of infection is not a well-documented sequelae of cabozantinib, although has been seen in other TKI’s, particularly for example Dabrafenib in melanoma [6]. In this report, we describe a case of refractory, high-grade fever with rigors in a patient recently commencing cabozantinib in the absence of any more plausible causative agent after detailed investigation.
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