Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Breast Neoplasms

Nausea

Vomiting

Breast Diseases

Skin Diseases

Signs and Symptoms, Digestive

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Palonosetron

Fosaprepitant

Aprepitant

Serotonin

Serotonin 5-HT3 Receptor Antagonists

Neurokinin-1 Receptor Antagonists

Substance P

Neurokinin A

Neurotransmitter Agents

patients receive oral palonosetron and aprepitant

patients receive intravenous palonosetron and fosaprepitant

oral aprepitant capsules 125mg for D1 before chemotherapy, 80mg for D2 and D3

oral palonosetron 0.5mg for D1 before chemotherapy; intravenous palonosetron 0.25mg for D1 before chemotherapy;

intravenous fosaprepitant 150mg for D1 before chemotherapy

Wei Tian, doctor

Chemotherapy is one of the most common treatments for breast cancer, but the adverse effects can be severe enough to delay or make chemotherapy intolerable, thus affecting the efficacy of the disease. Women and younger patients are more likely to experience chemotherapy-induced nausea and vomiting (CINV) . Therefore, antiemetic drugs is a key way to reduce chemotherapy side effects, which ensures compliance, and maintain quality of life. CINV is usually induced by two pathways. The central pathway is mediated by neurokinin-1 (NK-1) receptors, where chemotherapeutic agents stimulate the secretion of substance-P (SP) from the vomiting center located in the medulla oblongata and nucleus accumbens, which binds to NK-1 receptors and induces vomiting. The peripheral pathway is mediated by 5-hydroxytryptamine 3 (5-HT3) receptors, and chemotherapy stimulates intestinal chromophores in the gastrointestinal mucosa to secrete 5-HT3, which binds to its receptors to induce vomiting.

Most guidelines currently recommend the combination of 5-HT3 receptor antagonists, NK-1 receptor antagonists, and dexamethasone for high-emetogenic-risk chemotherapy regimens. Usually 5-HT3 receptor antagonists include granisetron, ondansetron, and palonosetron. Palonosetron is a second-generation 5-HT3 receptor antagonist with stronger affinity and higher efficacy than other antagonists. The commonly used NK-1 receptor antagonists are aprepitant and fosaprepitant. Fosaprepitant is an aprepitant prodrug that can be rapidly converted to aprepitant in the body, blocking the binding of substance P to NK-1 receptors for antiemetic purposes. Clinical trial has confirmed that the overall complete response (CR) rate of palonosetron 0.75 mg combined with fosaprepitant and dexamethasone was 54.9%, with 75.9% CR in the acute phase (0-24 h after chemotherapy) and 62.3% in the delayed phase (24-72 h after chemotherapy). Another clinical trial showed an acute phase CR of 89.8% and a delayed phase CR of 90.4% for oral aprepitant combined with intravenous palonosetron 0.75 mg and dexamethasone. The data suggests that both oral and intravenous administration are effective in preventing CINV, but there are no clinical trial results for oral versus intravenous administration. Oral administration is painless, has fewer side effects, and is a safer mode of administration, but bioavailability is different and drug absorption is affected by a variety of factors; whereas intravenous injection has rapid onset of action, but there are risks of injection reactions, phlebitis, and infection. Therefore, we hope to conduct a non-inferiority study on the efficacy of oral and intravenous 5-HT3 receptor antagonists combined with NK-1 receptor antagonists through this trial, which can provide more options for patients by combining the cost and administration methods.

Efficacy and Safety of Intravenous Versus Oral 5-HT3 Antagonists Combined With NK-1 Receptor Antagonists for the Prevention of CINV in Breast Cancer

Efficacy and Safety of Intravenous Versus Oral 5-HT3 Antagonists Combined With NK-1 Receptor Antagonists for the Prevention of Breast Cancer Chemotherapy-induced Nausea and Vomiting: a Single-center, Randomized Controlled Clinical Trial

No vomiting or additional antiemetic medication throughout the post-chemotherapy period (0-72 hours)

Delayed phase (24-72 hours after chemotherapy) without vomiting or additional antiemetic medication use

Acute phase (0-24 hours after chemotherapy) without vomiting or additional antiemetic medication use

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Efficacy and Safety of Intravenous Versus Oral 5-HT3 Antagonists Combined With NK-1 Receptor Antagonists for the Prevention of CINV in Breast Cancer	NCT05841849	Breast Cancer Chemotherapy-in...	Aprepitant Palonosetron Fosaprepitant	18 Years - 70 Years	Second Affiliated Hospital, School of Medicine, Zhejiang University
Efficacy and Safety of Intravenous Versus Oral 5-HT3 Antagonists Combined With NK-1 Receptor Antagonists for the Prevention of CINV in Breast Cancer	NCT05841849	Breast Cancer Chemotherapy-in...	Aprepitant Palonosetron Fosaprepitant	18 Years - 70 Years	Second Affiliated Hospital, School of Medicine, Zhejiang University

Spots Global Cancer Trial Database for oral versus intravenous