Safety
ketoacidosis, liver dysfunction, fatigue, necrotic, nasopharyngeal necrosis, ICA occlusion, headache, necrosis, epistaxis, hypertension
KETOACIDOSIS, NECROTIC, HAND-FOOT SYNDROME, NECROSIS, EPISTAXIS, HYPERTENSION
All patients experienced at least one treatment-related AE (TRAE). Grade 3-4 TRAEs were observed in 34 patients (58.6%), and the most common TRAEs were hypertension (19.0%), nasopharyngeal necrosis (15.5%), headache (12.1%), AST elevation (10.3%), and creatine phosphokinase elevation (10.3%; Table Adverse EventsFifty-one patients (87.9%) required one or more interruptions for apatinib, and dose reductions were observed in 26 patients (44.8%). The most common reasons for apatinib dose reductions were headache (n = 11; 19.0%) and liver dysfunction (n = 7; 12.1%). Owing to AEs, 16 patients terminated apatinib ahead of progression: 11 complied with medical advice because of grade 3-4 nasopharyngeal necrosis (n = 9; 56.3%), clinical worsening (n = 1; 6.3%), or debridement for necrosis (n = 1; 6.3%); three paused apatinib because of grade 3-4 liver dysfunction (n = 2; 12.5%) or ketoacidosis (n = 1; 6.3%) and then progressed before restarting; and two refused further administration, although the AEs were manageable (grade 2 epistaxis plus grade 3 hand-foot syndrome and fatigue plus dyspepsia).Five patients did not undergo a post-treatment endoscopic evaluation, and the assessment of nasopharyngeal necrosis was available in 53 patients, with 18 developing it. The median time to the occurrence of necrosis was 2.3 months (range, 0.7-9.2 months). The correlation test revealed a significant positive correlation between necrosis and recurrent nasopharyngeal lesions (OR, 5.94 [95% CI, 1.45 to 24.24]; especially recurrent T3-4) or nasopharyngeal reirradiation (OR, 5.33 [95% CI, 1.15 to 24.79]; Data Supplement). Among the 18 patients with nasopharyngeal necrosis, one underwent ICA embolization when the necrotic foci invaded (grade 4 necrosis, Data Supplement); two had necrosis devouring the ICAs, with ICA occlusion spontaneously (grade 4 necrosis, Data Supplement) or embolization before enrollment; six had grade 1-2 epistaxis; and two developed grade 3-4 epistaxis attributed to necrosis invading the internal jugular veins (conjectured) or the descending palatine artery, which were cured by nasal packing or vascular embolization (Data Supplement).