Chemotherapy-induced Nausea and Vomiting
Conditions
Keywords
Nausea, Vomiting, Glucocorticoids, Olanzapine, Tropisetron, Fosaprepitant, Signs and Symptoms, Digestive, Antiemetics, Physiological Effects of Drugs
Brief summary
To evaluate the efficacy and safety of a fosaprepitant, tropisetron, and olanzapine antiemetic regimen, with or without dexamethasone, in patients receiving highly emetogenic chemotherapy with epirubicin and cyclophosphamide.
Detailed description
Patients in this study were randomly assigned in a 1:1 ratio to one of two groups using an interactive response system with permuted blocks of four, stratified by age (\<55 vs. ≥55 years). They received either a three-drug antiemetic regimen with fosaprepitant, tropisetron, and olanzapine (triple group) or a four-drug regimen including fosaprepitant, tropisetron, olanzapine, and dexamethasone (quadruple group). All patients were hospitalized for approximately 120 hours post-chemotherapy, documenting emetic episodes, rescue medication use, and nausea ratings on a Likert scale (0 = no nausea, 1 = mild nausea, 2 = moderate nausea, 3 = severe nausea) in a diary. Rescue therapy was available as needed. Clinical staff monitored adverse events every 24 hours using National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Subjects who initiated treatment were followed up for endpoints, including complete response (CR), complete control (CC), total control (TC), quality of life, and safety assessments.
Interventions
DRUGFosaprepitant, tropisetron, and olanzapine-based antiemetic regimen
Fosaprepitant 150 mg intravenously on Day 1, tropisetron 5 mg intravenously on Day 1, and olanzapine 5 mg orally on Days 1 to 4.
DRUGFosaprepitant, tropisetron, olanzapine, and dexamethasone-based antiemetic regimen
Fosaprepitant 150 mg intravenously on Day 1, tropisetron 5 mg intravenously on Day 1, and olanzapine 5 mg orally on Days 1 to 4. Dexamethasone 12 mg on Day 1, followed by 8 mg on Days 2 to 4.
Sponsors
Henan Cancer Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Breast cancer patients receiving their first anthracycline/cyclophosphamide-based HEC regimen (cyclophosphamide 600 mg/m², epirubicin 90-100 mg/m²); divided doses excluded. 2. No prior chemotherapy. 3. Aged 18-70 years. 4. ECOG performance status 0 or 1. 5. Adequate organ function: (including absolute neutrophil count≥1,500/mm3, WBC count≥3,000/mm3, platelet count≥100,000/mm3, AST\< 2.5×the upper limit of normal (ULN), ALT\< 2.5×ULN, bilirubin\< 1.5×ULN, creatinine\< 1.5×ULN). 6. No nausea or vomiting within 24 hours before registration. 7. Negative pregnancy test within 7 days prior (women of childbearing potential). 8. No severe cognitive impairment. 9. No hypersensitivity to fosaprepitant, tropisetron, olanzapine, and dexamethasone. 10. No significant cardiac issues: arrhythmia, recent heart failure, or myocardial infarction within 6 months. 11. No symptomatic brain metastasis or carcinomatous meningitis. 12. No diabetes requiring insulin or oral medication. 13. No use of prohibited medications within 48 hours before registration or during treatment. 14. Informed consent obtained.
Exclusion criteria
1. History of allergic reactions to study drugs or their analogues. 2. Nausea and vomiting requiring antiemetic treatment at registration. 3. Pregnant or nursing women, those who may become pregnant, or those not planning to use contraception. 4. Mental illness or psychiatric symptoms interfering with daily activities, making study participation difficult. 5. Diabetes treated with insulin/oral hypoglycemics or HbA1c (NGSP) ≥ 6.5% or HbA1c (JDS) ≥ 6.1% at registration. 6. Recent (within 6 months) unstable angina, myocardial infarction, cerebral hemorrhage, cerebral infarction, or active gastroduodenal ulcer. 7. Convulsive disorders requiring anticonvulsants, ascites needing therapeutic puncture, or gastrointestinal obstruction. 8. Inability to be hospitalized for up to 120 hours (Day 6) post-AC administration initiation. 9. Any other conditions deemed inappropriate for study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete response rate (CR) during overall (0-120 hours after the initiation of anthracycline/cyclophosphamide administration) phase. | 0-120 hours after the initiation of anthracycline/cyclophosphamide administration | CR was determined by the absence of any retching or vomiting and the absence of any requirement for additional antiemetic treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete control rate (CC) during the acute, delayed, and overall phase | Day 1 to day 5 after the initiation of anthracycline/cyclophosphamide administration | CC is defined as a condition in which a patient does not report more than mild nausea (0 or 1 on a 4-grade categorical scale) (0 = no nausea, 1 = mild nausea, 2 = moderate nausea, 3 = severe nausea). |
| Total control rate (TC) during the acute, delayed, and overall phases | Day 1 to day 5 after the initiation of anthracycline/cyclophosphamide administration | TC is defined as a condition in which a patient does not report any nausea (0 on a 4-grade categorical scale) (0 = no nausea, 1 = mild nausea, 2 = moderate nausea, 3 = severe nausea). |
| CR during the acute (0-24 hours after the initiation of anthracycline/cyclophosphamide administration) and delayed (24-120 hours after the initiation of anthracycline/cyclophosphamide administration) phase | 0-24 hours and 24-120 hours after the initiation of anthracycline/cyclophosphamide administration | CR was determined by the absence of any retching or vomiting and the absence of any requirement for additional antiemetic treatment. |
| Quality of life based on Functional Living Index-Emesis (FLIE) assessment | 0-120 hours after the initiation of anthracycline/cyclophosphamide administration | Quality of life based on Functional Living Index-Emesis (FLIE) assessment in the overall phase (0-120 h). |
| Exploratory endpoints-The time to the treatment failure | 0-120 hours after the initiation of anthracycline/cyclophosphamide administration | The time to the treatment failure (time to first emetic episode or time to first use of rescue medication, whichever occurred first). |
| Safety outcomes | Day 1 to day 5 after the initiation of anthracycline/cyclophosphamide administration | Adverse event incidence rate |
Countries
China
Outcome results
None listed