Sunitinib related osteonecrosis of the jaw (SURONJ): a rare occurrence?

Abstract

Sir, Sunitinib is a drug approved in 2006 by the FDA for the treatment of renal cell carcinoma (RCC) and resistant gastrointestinal stromal tumor (GIST). The capillary endothelium is the first target of sunitinib: it blocks several pathways central to proliferation, migration, differentiation, neoangiogenesis, and invasion of cancer cells, including vascular endothelial growth factor receptors (VEGFRs), plateletderived growth factor receptors (PDGFR-α and PGRF-β), the stem cell factor receptor (c-Kit) and the Fms-like tyrosine kinase 3 (FLT3), and glial cell–derived neurotrophic factor receptor (RET), colony-stimulating factor type 1 (CSF-1R) [1, 2, 9]. In literature, several adverse effects of sunitinib have been described (pain, fatigue, hypertension, gastrointestinal toxicity, proteinuria, neurotoxicity, coagulation disorders, mucositis, hypothyroidism, nausea, diarrhea, altered taste, skin abnormalities and, rarely, osteonecrosis) but its long-term side effects are not completely known [2]. We report a case of osteonecrosis of the jaw related to sunitinib hesitated in a multifragmentary fracture. A 62-years-old male patient presented with a painful and infected lesion to the cutaneous side of the left jaw of 1-month duration. Eleven years before, he experienced a radical left nephrectomy for a clear renal cell carcinoma, followed by a 6-month therapy with IFN and IL-2. Five years after nephrectomy, he developed a cutaneous metastasis on the left maxillary region that was removed. During the follow-up, few months later, imaging showed the presence of metastasis on the neck lymph nodes bilaterally. He underwent a 50 mg/day sunitinib therapy (Sutent®) for four consecutive weeks of therapy followed by 2weeks of discontinuation (4/2 scheme). The patient felt limited mouth opening since the beginning of sunitinib treatment and, 18 months later, the lesion appeared at the jaw and sunitinib has been discontinued. Accurate intraoral exam showed exposed bone measuring 7mm in diameter in the left jaw (Fig. 1) with swelling and slight purulent excretion. He had no previous history of bisphosphonate treatment. The patient had undergone dental extraction procedures and presented a complete healing of the mucosa 1 year before starting the therapy with sunitinib. The patient had difficulty in mastication but not in deglutition or phonation. He underwent antimicrobial rinses and broad-spectrum antibiotics (amoxicillin/clavulanic acid) treatment for 6 days as firstline drugs documented in the literature [3]. Dental panograph and CT scan revealed, in IV sextant, a multifragmentary fracture of the left horizontal branchof the jawwith dislocation of the stumps and diffuse trabecular bone hyperdensity due to reactive osteosclerosis with seizures bone (Fig. 2). The patient refused any invasive procedure as fixation of the fracture sowe performed a surgical sequestrectomy, ablation of the necrotic bone and a mucosal flap to cover the loss of substance. Thirty minutes prior to the operation, we administered i.v. antibiotic therapy with amoxicillin+clavulanic acid (1000+200 mg). Pathology revealed the presence of necrotic bone with osteomyelitis, while microbiological culture showed the presence of Streptococcus mitis sensitive to ofloxacine. The patient received oral antibiotics treatment with 400mg ofloxacine twice a day for 2 weeks. The patient returned for a follow-up visit after 1, 6, and 12 month: intraoral lesion was completely healed; he partially recovered mouth opening and normal alimentation. Osteonecrosis of the jaw (ONJ) constitutes a serious complication following radiation treatment of head/neck tumors, trauma, dental surgery procedures, odontogenic infections, chemotherapy for malignant diseases, and treatment with bisphosphonates [4, 5]. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) has been frequently discussed [4] because of its consequences on patient’s quality of life but its etiopathogenesis has not been completely elucidated.Various hypotheses suggest that inhibition * Carlo Melloni carlomelloni.unipa@gmail.com