Auricular Acupressure for Prevention of Chemotherapy-Induced Nausea and Vomiting in Patients Receiving Highly Emetogenic Chemotherapy

Chemotherapy-induced nausea and vomiting (CINV) remains one of the most common and distressing adverse effects experienced by patients receiving systemic anticancer therapy. Despite substantial advances in antiemetic prophylaxis, CINV continues to negatively affect nutritional status, treatment adherence, daily functioning, psychological well-being, and health-related quality of life. Patients receiving highly emetogenic chemotherapy (HEC), including anthracycline-cyclophosphamide-based regimens and cisplatin-containing regimens, remain at particularly high risk for both acute and delayed CINV.

Current international antiemetic guidelines recommend prophylactic antiemetic therapy consisting of a neurokinin-1 receptor antagonist, a 5-hydroxytryptamine-3 receptor antagonist, and dexamethasone for patients receiving HEC. Although guideline-recommended regimens have substantially improved emesis control, delayed-phase CINV (24-120 hours after chemotherapy) remains insufficiently controlled in a considerable proportion of patients. Delayed nausea is particularly challenging to manage and is frequently associated with impaired oral intake, reduced quality of life, increased healthcare utilization, and decreased willingness to continue planned anticancer treatment. Therefore, the identification of effective adjunctive interventions for improving delayed-phase CINV control remains an important unmet clinical need.

Auricular acupressure is a noninvasive intervention derived from traditional Chinese medicine. Through continuous stimulation of specific auricular acupoints, auricular acupressure may influence autonomic nervous system activity, gastrointestinal function, neuroendocrine regulation, and symptom perception. Auricular acupoint stimulation has been investigated as a complementary approach for the prevention and management of chemotherapy-induced nausea and vomiting in patients receiving anticancer treatment.

Previous clinical studies and systematic reviews have suggested that auricular acupressure may improve chemotherapy-related nausea and vomiting and reduce symptom burden in patients with cancer. However, the currently available evidence remains limited by methodological heterogeneity, small sample sizes, inadequate sham-control procedures, insufficient blinding, and inconsistent outcome assessment methods. In particular, relatively few rigorously designed randomized controlled trials have specifically focused on delayed-phase CINV, which remains one of the most difficult aspects of antiemetic management. Consequently, high-quality evidence regarding the efficacy and safety of auricular acupressure as an adjunct to contemporary guideline-based antiemetic prophylaxis remains insufficient.

The auricular acupoint prescription used in this study was developed in accordance with the auricular acupoint recommendations described in the 2025 Chinese Society of Clinical Oncology (CSCO) Guideline for the Prevention and Treatment of Antitumor Therapy-Induced Nausea and Vomiting. The intervention includes auricular acupoints such as Shenmen, Stomach, Sympathetic, and other protocol-specified points selected for the management of chemotherapy-induced nausea and vomiting.

This study is designed as a multicenter, randomized, double-blind, sham-controlled clinical trial to evaluate the efficacy and safety of auricular acupressure as an adjunct to standard triple antiemetic therapy in patients receiving highly emetogenic chemotherapy. Eligible participants will be randomly assigned in a 1:1 ratio to receive either active auricular acupressure or sham auricular acupressure in addition to guideline-recommended antiemetic prophylaxis. The sham-controlled design is intended to minimize expectation bias and improve the internal validity of the study.

The primary objective of this trial is to determine whether auricular acupressure improves delayed-phase control of chemotherapy-induced nausea and vomiting during the first cycle of highly emetogenic chemotherapy. The primary endpoint is the complete protection (CP) rate during the delayed phase (24-120 hours after chemotherapy), defined as no vomiting, no use of rescue antiemetic medication, and a nausea visual analogue scale (VAS) score below 25 mm. Compared with conventional endpoints that primarily focus on emesis control, complete protection incorporates both nausea severity and rescue medication use, thereby providing a more comprehensive assessment of clinically meaningful symptom control.

Secondary objectives include the evaluation of complete protection, complete response, total control, nausea severity, vomiting outcomes, rescue medication use, appetite changes, patient-reported outcomes, health-related quality of life, treatment adherence, and safety outcomes across multiple chemotherapy cycles. Validated patient-reported outcome instruments, including the Functional Living Index-Emesis (FLIE) and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), will be used to comprehensively assess symptom burden, functional impact, and quality of life.

By employing a multicenter design, rigorous randomization procedures, double blinding, standardized intervention protocols, guideline-based antiemetic therapy, and validated outcome measures, this study seeks to address important limitations of previous research and generate robust clinical evidence regarding the effectiveness and safety of auricular acupressure for the prevention of chemotherapy-induced nausea and vomiting. The findings of this trial are expected to contribute to the evidence base for integrative symptom management and support the optimization of CINV prevention strategies in patients receiving highly emetogenic chemotherapy.

Inclusion criteria

• Age 18-75 years, either sex.

• Malignant solid tumor confirmed by histopathology.

③ Chemotherapy-naïve, planned to receive a single-day intravenous highly emetogenic chemotherapy (HEC) regimen, including:

• Cisplatin-containing regimens (dose ≥50 mg/m²);
• Anthracycline plus cyclophosphamide (AC/EC) regimens;
• Carboplatin AUC ≥4;
• Other highly emetogenic chemotherapy regimens recognized by guidelines.

④ In accordance with guideline recommendations for HEC regimens, the triple regimen of NK-1 RA + 5-HT₃ RA + dexamethasone is used:

⑤ ECOG performance status score 0-1.

⑥ Life expectancy ≥ 6 months.

⑦ Voluntarily signed informed consent, and able to understand and complete the patient diary.

Exclusion criteria

• Nausea or vomiting already present within 24 hours prior to enrollment.

• Symptomatic brain metastases, gastrointestinal obstruction, or other organic diseases likely to cause nausea and vomiting.

• Local skin breakdown, infection, or deformity of the auricle, or allergy to adhesive tape/Vaccaria seeds (Wang Bu Liu Xing).

④ Planned use of olanzapine, thalidomide, or other antiemetic agents not specified in the protocol as part of the routine prophylactic antiemetic regimen during this chemotherapy cycle (i.e., those receiving a quadruple regimen or other non-standard prophylactic regimens).

⑤ Long-term regular use (e.g., more than 3 times per week) of benzodiazepines, antipsychotics, or sedative-hypnotics; or known history of drug abuse/dependence.

⑥ Severe mental illness or cognitive impairment that precludes cooperation with assessments.

⑦ Receipt of ear acupuncture or auricular acupressure (ear seeds) within 4 weeks prior to enrollment.

⑧ Pregnant or lactating women.