Efficacy and Safety of Aprepitant for the Prevention of Nausea and Emesis During Concurrent Chemoradiotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma (LA-HNSCC): A Phase 2 Trial

Abstract

Few studies reported effective interventions for preventing nausea and emesis caused by concurrent chemoradiotherapy (CCRT) in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). This prospective phase II study was performed to assess the safety and efficacy of the neurokinin-1-receptor antagonist (NK1-RA) aprepitant in LA-HNSCC patients receiving CCRT with high-dose cisplatin. Treatment-naïve LA-HNSCC patients received intensity-modulated radiotherapy with concurrent cisplatin 100 mg/m2 in 6.5 weeks. Cisplatin was divided into 3 days on day 1-3 every 3 weeks, in company with the antiemesis regimen. All patients were given orally aprepitant 125 mg once on d1, then 80mg once on d2-5; ondansetron 8 mg once on d1; and dexamethasone 12 mg once on d1, then 8mg on d2-5. The primary endpoint was complete response (CR) in the overall phase, defined as no emesis and no use of rescue therapy in this period. Rescue medication was permitted for ≥ grade 2 nausea and emesis. Per the Simon two-stage design, 17 patients are enrolled in stage 1; if ≥ 13 patients are CR, 26 additional patients are enrolled in stage 2. If CR rate is ≥ 80%, the trial is deemed positive. The study was registered with ClinicalTrials.gov, number NCT03572829. Between Jan 2018 and Jan 2020, 44 LA-HNSCC patients were enrolled. The median age was 53 years old (range, 18-66), and 86.4% were male. All patients fulfilled the radiotherapy and the first cycle of cisplatin. Cisplatin dose changes were reported in 11 (28.9%) of 38 patients during the second cycle, while other 6 patients terminated chemotherapy owing to the hematotoxicities and hepatotoxicities. Sixteen of 17 patients were CR in stage 1 and 27 patients were enrolled in stage 2. The overall CR rates was 88.6% (39/44). The CR rates in cycles 1 and 2 were 90.9% (40/44) and 92.1% (35/38), respectively. The overall rates of no emesis and no nausea were 88.6% (39/44) and 61.4% (27/44). Grade 2 emesis occurred in 3 patients (1 patient was rescued) and grade 1 in 2 patients. The median score of nausea was 4 (range, 1-10). The rates of no emesis in cycle 1 and 2 were 90.9% and 92.1%, respectively. The corresponding rates of no nausea were 61.4% and 78.9%, respectively. There was no ≥ grade 3 antiemesis treatment related adverse event. The major toxicities were constipation (17 patients, 38.6%) and hiccough (7 patients, 15.9%). Aprepitant in addition to ondansetron and dexamethasone significantly improve control of emesis and nausea in patients with LA-HNSCC receiving concomitant high-dose cisplatin and radiotherapy. Randomized phase 3 studies are necessary to further define the potential role of NK1-RA in this setting.