.jpg "Ya Liu, MD photo")
Ya Liu, MD
Beijing, Beijing
Purpose/Objective(s): The superiority of the triple antiemetic regimen of aprepitant, dexamethasone and ondansetron has been proved in our previous study (NCT03572829), in which the complete remission rate achieved 86% and and the incidence of no vomiting was 88.4%. However, there were no significant reduction in the incidence of nausea, and the rate of hiccups might caused by dexamethasone also reached 16.3%. This new phase 2 trial aimed to assess the safety and efficacy of a dexamethasone-free antiemetic regimen in LA-HNSCC patients undergoing CCRT with high-dose cisplatin.
Materials/Methods: Treatment-naive LA-HNSCC patients underwent intensity-modulated radiotherapy along with cisplatin 100 mg/m² over 6.5 weeks. Cisplatin was administered overthree days(day 1-3) every 3 weeks for two cycles, concomitant with the antiemesis regimen. All patients received aprepitant orally at a dose of 125 mg on day 1, followed by 80mg on days 2-3, palonosetron 0.25 mg on day 1; and olanzapine 5 mg daily on days 1-5. The primary endpoint was the incidence of nausea-free response throughout the study. Following the Simon two-stage design, 17 patients were enrolled in stage 1; if at least 13 patients exhibited no nausea, an additional 26 patients were enrolled in stage 2. Based on δ=0.2 and a=0.05, the anticipated nausea-free response rate was set at 80% and not less than 60%. The study was registered with ClinicalTrials.gov under the identifier NCT05202275.
Results: From January 2021 and Febuary 2023, 43 LA-HNSCC patients were enrolled as scheduled. The median age was 50 years(range, 25-64), and 76.7% were male. All patients received radiotherapy, while 5 patients discontinued chemotherapy due to adverse effect and one withdrew due to sudden cardiac death. Additionally, three patients declined to continue the antiemetic regimen as prescribed due to severe dizziness following olanzapine administration. Overall, 40 patients completed cycle 1, while 34 patients completed cycle 2.The overall nausea-free response rate was 65.0% (95% CI: 48.3%-79.4%), with rates of 72.5% (95% CI: 56.1%-85.4%) for cycle 1 and 76.5% (95% CI: 58.8%-89.3%) for cycle 2 .The overall emesis-free response rate was 85% (95% CI: 70.2%-94.3%). The overall complete protection rate and complete response rate were 87.5% (95% CI: 73.2%-95.8%) and 90.0% (95% CI: 76.3%-97.2%), respectively. Adverse events such as somnolence (30%), constipation (20%), and hiccups (12.5%) related to antiemetics use were all grade 1. No grade 4 or 5 treatment-related adverse events associated with antiemetic use was observed.
Conclusion: The triple regimen comprising aprepitant, palonosetron and olanzapine effectively prevented nausea and emesis in LA-HNSCC patients undergoing radiotherapy and concomitant high-dose cisplatin chemotherapy, while also reducing the incidence of dexamethasone-induced hiccups. Randomized phase 3 trials are warranted to elucidate the potential role of this combination in chemoradiotherapy setting.