the small molecule tyrosine kinase inhibitors ( tkis ) sunitinib and pazopanib are used as first - line agents in the treatment of metastatic renal cell carcinoma . despite proven efficacy , their use can be limited by treatment - related toxicities . we report a patient with metastatic renal carcinoma who developed trismus while being treated with these agents and is , to the best of our knowledge , the first such case to be reported . a 77-year - old male underwent radical nephrectomy for a 7 cm t2 fuhrman grade two left - sided clear cell renal carcinoma . eleven years postresection , a surveillance x - ray computed tomography ( ct ) scan revealed two pancreatic lesions , consistent with disease relapse . on the appearance of malignant lymphadenopathy on further imaging , a dose reduction was required at cycle three due to mucositis , but otherwise the treatment was generally well tolerated with minimal toxicity . serial ct scans showed evidence of objective disease response and subsequent disease stabilization [ figure 1 ] . ct scan to confirm no evidence of cerebral metastasis and no skull metastasis . also confirms no evidence of soft tissue metastasis , no bone metastasis and no metastasis within the mandible . within the inferior pole of the right lobe of the thyroid gland there is a well defined 12 mm nodule which is likely to be benign but needs further characterisation five years after commencing sunitinib , the patient developed stiffness of the jaw and difficulty opening his mouth , which worsened over the subsequent 2 weeks . eventually , his symptoms were so severe that he was only able to open his mouth wide enough to use a straw for drinking . speech and swallowing were unaffected , and there was no evidence of mucositis in the oral cavity . the patient had no history of jaw or dental problems and was not taking any other regular medication . head and neck imaging was unremarkable with no evidence of metastatic disease or other pathology . the patient initially continued with sunitinib treatment , but when he commenced his scheduled 2-week treatment break , his symptoms spontaneously resolved . on commencing the next cycle 2 weeks later , the same symptoms recurred , and once again resolved spontaneously on stopping treatment . a further staging ct scan revealed only a new adrenal metastasis , which was resected . several months later , on further disease progression , pazopanib was commenced . within a week , the trismus symptoms recurred , and once again resolved with cessation of the drug . no other tkis were used in the further management of this patient 's disease , and the trismus did not occur again . sunitinib and pazopanib act by antagonizing several growth factor receptors commonly found on the endothelial cells of tumor vasculature , including vascular endothelial growth factor receptor ( vegfr ) and platelet - derived growth factor receptor . their mechanism of action is competitive inhibition at the atp - binding domain , preventing phosphorylation at key tyrosine residues and thus blocking receptor activation . the effect , largely mediated through vegfr2 , is inhibition of angiogenesis , one of the core processes required for cancer cell survival and proliferation . although when initially developed , toxicity secondary to these agents was predicted to be low or nonexistent , as 99% of endothelial cells in an adult remain quiescent at any 1 time and only proliferate during wound healing or the menstrual cycle , a well - defined toxicity profile now exists for this group of drugs . this includes gastrointestinal toxicity , mucocutaneous effects including hand - foot syndrome and mucositis , hematological abnormalities ( anemia , leucopenia , and thrombocytopenia ) , hepatic enzyme elevation , and hypertension . contrary to previous assumptions , it is now clear that vegfr is not unique to the proliferating endothelial cell , and is present on many other cell types throughout the body . its involvement has been described in several hematological processes including coagulation and hematopoeiesis , and in organs including the thyroid gland , kidney , and bone . most of the treatment toxicities noted therefore appear to be  on target  effects , secondary to the presence of vegfr at these sites . the precise mechanism of mucocutaneous toxicity is not completely understood but is likely a combination of impaired wound healing , microhemorrhage and impaired endothelial cell proliferation , secondary to the presence of vegfr on the endothelial cells of dermal capillaries . lockjaw  can be defined as progressive tonic contraction of the muscles of mastication that results in decreased mouth opening . common causes include trauma , infections , disorders of the temporomandibular joint such as arthritis , submucosal fibrosis , dental treatment , and in the oncology patient , direct invasion of the temporomandibular joint or muscles of mastication by tumors and head and neck radiotherapy . in addition , several drugs have been associated with the condition , including tricyclic antidepressants , phenothiazines , and succinylcholine . other antiangiogenic agents , including the monoclonal antibody bevacizumab which also targets vegfr , are similarly not commonly associated with trismus . there has been only one study which described seven patients on bevacizumab who developed tetany - like symptoms , one of whom presented with jaw stiffness . however , both sunitinib and bevacizumab are associated with osteonecrosis of the jaw in patients with renal cell carcinoma , both in conjunction with but also independent of simultaneous bisphosphonate therapy . this indicates that these agents can penetrate bone tissue and that the mandible appears to be particularly susceptible to their effects , as osteonecrosis in other bony sites secondary to tki use is rare . in addition , vegf has other roles within the bone in addition to affecting vascularity , including osteoblast differentiation and enhancement of osteoclast - mediated bone resorption and therefore it is conceivable that the trismus experienced by this patient was a result of vegf blockade with the body of the mandible or within the temporomandibular joint . our patient developed trismus as a complication of sunitinib therapy 5 years after commencing treatment for metastatic renal cell carcinoma . this unusual symptom was related to drug exposure and also recurred when changing sunitinib to another tki pazopanib . this is the first report of trismus as a direct toxicity of any tki agent for any indication .
tyrosine kinase inhibitors sunitinib and pazopanib are used as first - line agents in the treatment of metastatic renal cell carcinoma . 
 treatment - related toxicities have been described with both these drugs . 
 this report describes a patient with metastatic renal carcinoma who developed trismus while being treated with these agents and is , to the best of our knowledge , the first such case to be reported .