Single low-dose 5-mg versus 8-mg dexamethasone with NEPA for the 168-h prevention of highly or moderately emetogenic (high-risk patients) chemotherapy-induced nausea/vomiting: An open-label, randomised, controlled, phase 3 trial.

Abstract

12072 Background: Tailoring Dexamethasone (DEX) dosing to reduce corticosteroid exposure is a challenging issue in the chemotherapy induced nausea /vomiting(CINV) management. This study aims to identify the efficacy of single low-dose 5mg versus 8mg dex with nepa for the 168h prevention of highly or moderately emetogenic (high-risk patients) CINV. Methods: This open-label, randomized trial compared the efficacy and safety of 5 mg versus 8 mg DEX regimens, both with NEPA, in patients receiving MEC or HEC chemotherapy. Patients were 1:1 randomized to 5 mg or 8 mg groups. The primary endpoint was complete response (no emesis, no rescue medication) from 0 to 168 hours. Secondary endpoints included total control, complete control, and daily CINV incidence. This study was registered with ChiCTR2400089311. Results: From June 20, 2024 to June 20, 2025, a total of 164 eligible individuals were assigned at random to the 5 mg or 8 mg DEX treatment arms.Primary efficacy endpoints:The overall CR rates for the prevention of CINV, observed throughout the study period, were 91.7% in the 5 mg group and 92.5% in the 8 mg group ( P =0.400) . In the acute phase, the CR rates were 97.9% for the 5 mg group and 97.5% for the 8 mg group ( P =1.000). During the delayed phase, the CR rates were 91.7% for the 5 mg group and 92.5% for the 8 mg group ( P =1.000). In the long-delayed phase, the CR rates were 93.8% for the 5 mg group and 97.5% for the 8 mg group ( P =0.744). Secondary efficacy endpoints: During the whole observation period, the total control rates were 77.1% for the 5 mg group and 62.5% for the 8 mg group ( P =0.208); the complete control rates were 85.4% for the 5 mg group and 87.5% for the 8 mg group( P =1.000). Secondary safety endpoints: The safety profiles of both dosages were similar and majority of treatment-related adverse events (TRAEs) were mild to moderate (grades 1 or 2), with no significant differences in the occurrence or severity of TRAEs (hyperglycemia, indigestion/heartburn or reflux and constipation, prevalence of QTcB interval prolongation or increase ect) would warrant particular concern. Conclusions: This study identify single low-dose 5mg DEX is equally effective as 8mg DEX with NEPA for the 168h Prevention of HEC or MEC (high-risk patients) CINV. Moreover, the 5mg DEX group has better therapeutic safety. It offers evidence-based recommendations for using a lower dose of DEX in combination with NEPA for the prevention and treatment of CINV. These promising results pave the way for reduction of DEX in antiemetic care. Clinical trial information: ChiCTR2400089311 .