title: Osteonecrosis of the jaw associated with ziv-aflibercept.
abstract: 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.
authors.affiliation: 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.
authors.forename: Hani
authors.initials: H
authors.lastname: Mawardi
authors.affiliation: Center for Esophageal and Gastric Cancer, Dana Farber Cancer institute, Boston, MA, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Enzinger
authors.affiliation: Deptment of Medical Oncology, Dana Farber Cancer institute, Boston, MA, USA.
authors.forename: Nadine
authors.initials: N
authors.lastname: McCleary
authors.affiliation: Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA.
authors.forename: Reshma
authors.initials: R
authors.lastname: Manon
authors.affiliation: 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.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Villa
authors.affiliation: 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.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Treister
authors.affiliation: 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.
authors.forename: Sook-Bin
authors.initials: SB
authors.lastname: Woo
keywords: Osteonecrosis; jaw; ziv-aflibercept