Auricular Point Stimulation Plus Dexamethasone for Nausea and Vomiting Caused by Trastuzumab Deruxtecan

Official title

Auricular Point Stimulation Plus Dexamethasone for Nausea and Vomiting Caused by Trastuzumab Deruxtecan in Breast Cancer Palliative Therapy

Overview

The goal of this clinical trial is to learn if auricular point stimulation plus dexamethasone works to effectively prevent or suppress nausea and vomiting caused by trastuzumab deruxtecan in breast cancer palliative therapy. It will also learn about the safety and influence on gastrointestinal function of auricular point stimulation plus dexamethasone. The main questions it aims to answer are: Can auricular point stimulation plus dexamethasone effectively prevent or suppress nausea and vomiting induced by trastuzumab deruxtecan? Can auricular point stimulation plus dexamethasone effectively reduce the incidence of appetite loss, weakened or disordered gastrointestinal function, and other uncomfortable conditions caused by excessive use of antiemetic drugs? Participants will: Receive auricular acupressure with bean seeds on specific points of one ear, plus intravenous injection of dexamethasone as a preventive antiemetic treatment within half an hour before trastuzumab deruxtecan treatment. Starting from the day of trastuzumab deruxtecan treatment (Day 1) to the following five days (Day 1-Day 5), provide regular stimulation at the acupressure points daily by themselves according to the protocol provided in this trial. Record their nausea and vomiting status, appetite, and gastrointestinal function-related symptomatic indicators from Day 1 to Day 5. Oral antiemetics are also prepared. If nausea and vomiting are significant or the patient feels the need, they may be temporarily administered as an adjunct.

Detailed description

Trastuzumab deruxtecan is an important therapeutic agent in the palliative treatment of advanced breast cancer. It is used as first-line therapy for HER2-positive advanced breast cancer in patients who have previously received anti-HER2 treatment, as well as second-line or later therapy for advanced or recurrent breast cancer. Additionally, it is the first targeted therapy approved in China for HER2-low advanced breast cancer. While it improves patient survival rates, it is also associated with certain gastrointestinal adverse reactions, with treatment-related nausea and vomiting being particularly common, occurring in nearly 80% of cases. The majority of these symptoms occur on the day of administration and within the following four days. This regimen is currently classified as a high emetic risk treatment in clinical guidelines. The recommended prophylactic antiemetic strategy typically involves a quadruple regimen combining corticosteroids (e.g., dexamethasone), 5-HT3 receptor antagonists (e.g., ondansetron, palonosetron), NK1 receptor antagonists (e.g., fosaprepitant, aprepitant), and the antipsychotic drug olanzapine. However, in clinical practice, many patients experience drug-related gastrointestinal adverse reactions such as anorexia, bloating, constipation, and diarrhea due to the use of high-intensity antiemetic therapy. Studies have shown that the incidence of constipation in chemotherapy patients treated with palonosetron nearly doubles. The aggressive use of antiemetics severely impacts patients' gastrointestinal function, quality of life, and even their treatment adherence. Therefore, how to effectively prevent trastuzumab deruxtecan -induced nausea and vomiting while minimizing the side effects of antiemetic therapy itself has become a practical issue that healthcare professionals urgently need to address.

Auricular point pressotherapy is a traditional Chinese medicine (TCM) external therapy. It involves accurately pasting Vaccaria seeds on corresponding auricular points with adhesive tapes and stimulating the points through moderate pressing to regulate physical functions and treat diseases. According to TCM theory, the ear is closely connected to the internal organs and meridians of the human body, and all twelve meridians are directly or indirectly linked to the ear. Auricular point pressotherapy can unblock meridians and balance yin and yang by stimulating corresponding auricular points, thereby alleviating anti-cancer therapy-related nausea and vomiting and other adverse reactions. It is an economical, non-invasive, and low-side-effect natural therapy. Meanwhile, auricular point pressotherapy can effectively improve gastrointestinal function, thus significantly reducing gastrointestinal dysfunction caused by chemotherapy and antiemetic drugs, such as anorexia, abdominal distension, constipation, and diarrhea.

Our team summarized the relevant data of patients who voluntarily received auricular point pressotherapy for antiemesis previously. The results showed that among breast cancer patients who received trastuzumab deruxtecan. 100% of those treated with auricular point pressotherapy plus dexamethasone did not experience grade 2 or above (including grade 2) nausea and had no vomiting on the day of medication and within 3 days thereafter.

Based on the theoretical and practical foundation described above, this study aims to evaluate the efficacy and safety of auricular point pressing with beans combined with dexamethasone in preventing and suppressing nausea and vomiting induced by trastuzumab deruxtecan in the palliative treatment of breast cancer. It will also assess patient appetite, gastrointestinal function, and other related indicators, exploring the important role of integrated traditional Chinese and Western medicine interventions in improving the quality of life of patients during antitumor therapy. The findings are expected to provide clinical references for optimizing the management of adverse reactions associated with trastuzumab deruxtecan.

Interventions

• Other Auricular point stimulation plus dexamethasone
  On the day of trastuzumab deruxtecan treatment (d1): Within half an hour before chemotherapy, administer auricular acupressure on one ear (stimulating the stomach, cardia, and brainstem acupoints for 5 minutes each) along with an intravenous push of 5 mg dexamethasone. From the day of chemotherapy (d1) to the following five days (d1-d5): Stimulate each acupoint once in the morning, noon, and evening, for 5 minutes each time. If nausea or vomiting occurs, immediately apply additional stimulation

Primary outcome measures

• Proportion of patients experiencing nausea as assessed by NIC-CTC AE4.0 [Time frame: from the day of trastuzumab deruxtecan treatment (Day 1) until the end of Day 5]

Secondary outcome measures (2)

• Proportion of patients experiencing vomiting as assessed by NIC-CTC AE4.0 [Time frame: from the day of trastuzumab deruxtecan treatment (Day 1) until the end of Day 5]
• Proportion of patients requiring additional antiemetics [Time frame: from the day of trastuzumab deruxtecan treatment (Day 1) until the end of Day 5]

Eligibility criteria

Inclusion Criteria: Patients must meet the following inclusion criteria for the study:

• Age ≥ 18 years and ≤ 85 years;
• Breast cancer patients scheduled to undergo palliative treatment with trastuzumab deruxtecan;
• ECOG performance status score of 0-2;
• Normal hematological function (platelet count > 80×10⁹/L; white blood cell count > 3×10⁹/L; neutrophil count > 1.5×10⁹/L);
• Serum bilirubin ≤ 1.5 times the upper limit of normal (ULN), and transaminase ≤ 5 times the ULN;
• No ascites, no gastrointestinal obstruction, normal coagulation function, and serum albumin ≥ 30g/L;
• Child-Pugh classification of liver function is Grade A;
• Serum creatinine < ULN, or calculated creatinine clearance rate > 50ml/min.

Exclusion Criteria: Patients who meet any of the following criteria will be excluded from the study:

• Local inflammation or infection of the auricle;
• Bleeding tendency or coagulation disorders;
• Severe ascites;
• Gastrointestinal obstruction;
• Hypertensive crisis or hypertensive encephalopathy;
• Severe uncontrolled systemic complications such as infection or diabetes mellitus;
• Clinically severe cardiovascular diseases, including cerebrovascular accident (within 6 months before enrollment), myocardial infarction (within 6 months before enrollment), hypertension that is not well-controlled despite appropriate medication, unstable angina pectoris, congestive heart failure (NYHA Class 2-4), and cardiac arrhythmias requiring drug treatment;
• A history of or physical examination findings indicating central nervous system diseases (e.g., primary brain tumor, epilepsy uncontrolled by standard treatment, any history of brain metastasis or stroke);
• Hypersensitivity to any drugs used in the study;
• Pregnant or lactating women;
• Presence of any other diseases, functional impairment caused by metastatic lesions, or suspicious disorders identified during physical examination, which suggest contraindications to the study drugs or place the patient at high risk of treatment-related complications;
• Inability or unwillingness to comply with the study protocol.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Prevention

Study locations

China · 1 center

• Second Affiliated Hospital of Zhejiang University School of Medicine — Hangzhou

Publications

• Stankowicz M, Mauro L, Harnden K, Pennisi A. Management of Chemotherapy-Induced Nausea and Vomiting with Trastuzumab Deruxtecan: A Case Series. Breast Care (Basel). 2021 Aug;16(4):408-411. doi: 10.1159/000511049. Epub 2020 Oct 23. PMID 34602948

Identifiers

NCT: NCT07537673 · 20251807

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗