Mawardi Hani, Enzinger Peter, McCleary Nadine, Manon Reshma, Villa Alessandro, Treister Nathaniel, Woo Sook-Bin
Division of Oral Medicine and Dentistry, Brigham and Women's Hospital, Boston, MA, USA;; Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA;; Department of Oral Medicine, Infection and Immunity, King Abdulaziz University, Jeddah, Saudi Arabia.
Center for Esophageal and Gastric Cancer, Dana Farber Cancer institute, Boston, MA, USA.
J Gastrointest Oncol. 2016 Dec;7(6):E81-E87. doi: 10.21037/jgo.2016.05.07.
Medication-related osteonecrosis of the jaw (MRONJ) has been associated with medications that include bisphosphonates (BPs), denosumab, bevacizumab and sunitinib. Ziv-aflibercept is a recombinant human vascular endothelial growth factor (VEGF) receptor which has been used to treat patients with various advanced solid tumors. We report three patients without a history of the use of medications known to cause MRONJ presenting with jaw osteonecrosis typical for MRONJ following therapy with ziv-aflibercept. All patients had metastatic gastrointestinal cancer treated with ziv-aflibercept and were evaluated for MRONJ because of exposed bone in the oral cavity. None of the patients had received antiresorptive therapies or any other medication known to cause MRONJ, and none had received radiation therapy to the jaws. Patients were aged 43, 51, 63 and all were males. Patients received 7, 16 and 23 cycles of ziv-aflibercept treatment and developed necrotic bone. All three patients presented with mandibular involvement, with two reporting pain. Patients were managed with anti-microbial mouth rinse, antibiotics and non-surgical sequestrectomy and followed up for 1.5, 2, and 2 months; two patients became asymptomatic while one patient continued to have pain. These three reported patients with a history of ziv-aflibercept therapy and no reported use of other medications known to cause MRONJ developed exposed necrotic bone of the jaw. We believe that ziv-aflibercept is another medication that can potentially cause MRONJ probably through its anti-VEGF activity, similar to bevacizumab and sunitinib.
药物相关性颌骨坏死（MRONJ）与包括双膦酸盐（BP）、地诺单抗、贝伐单抗和舒尼替尼在内的药物有关。 阿柏西普是一种重组人血管内皮生长因子（VEGF）受体，已被用于治疗各种晚期实体瘤患者。 我们报告了3例既往无已知可导致MRONJ药物使用史的患者，在接受阿柏西普治疗后出现典型的MRONJ颌骨坏死。 所有患者均患有转移性胃肠道癌并接受阿柏西普治疗，因口腔骨质暴露而接受MRONJ评估。 所有患者均未接受过抗吸收治疗或任何其他已知可导致MRONJ的药物，也未接受过颌骨放射治疗。 患者年龄分别为43岁、51岁、63岁，均为男性。 患者接受了7、16和23个周期的阿柏西普治疗并出现骨坏死。 所有3例患者均有下颌骨受累，2例报告有疼痛。 患者接受抗菌漱口水、抗生素和非手术死骨切除术治疗，并随访1.5、2和2个月；2例患者无症状，1例患者持续疼痛。 这3例报告的患者有阿柏西普治疗史，且未报告使用过其他已知可导致MRONJ的药物，均出现了颌骨暴露性坏死骨。 我们认为，阿柏西普可能是另一种可导致MRONJ的药物，其作用可能与贝伐单抗和舒尼替尼类似，是通过其抗VEGF活性实现的。
