Megestrol Acetate Versus Dexamethasone to Prevent Nausea and Vomiting in Oxaliplatin-Based Chemo

03 Apr 20266 min read0 viewsJournal Feed

GIST (Key Takeaways)

Introduction Oxaliplatin is widely used in the treatment of gastric and gastro-oesophageal junction cancer. However, oxaliplatin-induced nausea and vomiting often complicate treatment and negatively affect patients' quality of life.
The current standard antiemetic regimen - dexamethasone (DEX) plus palonosetron - offers only limited efficacy, benefiting approximately 70% of patients, and is associated with steroid-related adverse effects, including insomnia and gastrointestinal bleeding. Consequently, there is a clear clinical need for effective DEX-free antiemetic regimens.
This study aims to evaluate the efficacy and safety of megestrol acetate versus DEX in preventing oxaliplatin-induced nausea and vomiting in patients with gastric or gastro-oesophageal junction cancer. Method and analysis This is an investigator-led, multicentre, randomised-controlled, open-label, phase III, non-inferiority trial.
Chemotherapy-naïve patients scheduled to receive oxaliplatin-based chemotherapy are randomly (1:1) assigned to receive either megestrol acetate (megestrol acetate group) or DEX (DEX group) in combination with palonosetron. The primary endpoint is the complete response (CR; no vomiting and no rescue therapy) rate during the first 120 hours following the initiation of chemotherapy (0 - 120 hours).

Objective and clinical question:
The trial seeks to determine whether megestrol acetate can match dexamethasone in preventing oxaliplatin-associated nausea and vomiting in patients with gastric or gastro-oesophageal junction cancer.
The motivation is to identify a DEX-free antiemetic option due to limited efficacy of the standard regimen (DEX plus palonosetron) and the adverse effects linked to dexamethasone.
Design and scope:
This is an investigator-led, multicentre, randomized, open-label, phase III study employing a non-inferiority framework.
Participants are chemotherapy-naïve and are assigned in a 1:1 ratio to either the megestrol acetate arm or the dexamethasone arm, both in combination with palonosetron.
The trial is structured to evaluate antiemetic performance within the context of oxaliplatin-based chemotherapy for gastric or gastro-oesophageal junction cancers.

Primary outcome:
Complete response (CR), defined as no vomiting and no need for rescue therapy, assessed during the first 120 hours (0–120 hours) after initiation of chemotherapy.
Secondary outcomes:
CR during the acute phase (0–24 hours) and the delayed phase (24–120 hours).
Time to treatment failure and frequency of salvage medication use.
Patient-reported and clinical safety metrics, including adverse events and quality of life.

Population:
Adults with gastric or gastro-oesophageal junction cancer planned to receive oxaliplatin-based chemotherapy.
The study targets individuals naïve to chemotherapy at enrollment.
Interventions:
Megestrol acetate group: megestrol acetate administered in combination with palonosetron.
DEX group: dexamethasone in combination with palonosetron.
Comparative framing:
The non-inferiority aim centers on whether megestrol acetate provides a CR comparable to dexamethasone across the specified time windows.

Ethics:
The protocol adheres to the Declaration of Helsinki and has received ethics approval from the Certified Review Board of West China Hospital, Sichuan University (Approval No 1116/2023).
Dissemination plans:
Results are intended for presentation at scientific meetings and for publication in peer-reviewed journals.

Evidentiary scope:
The content provided outlines study rationale, design, endpoints, and planned dissemination but does not include results, numerical data, or effect estimates.
Unreported elements:
Specific dosing regimens, the precise oxaliplatin-based regimens used, and anticipated sample size or statistical margins are not described in the text.
Long-term outcomes beyond 120 hours and detailed safety signals are not reported.