Efficacy of an Olanzapine Based Dexamethasone-sparing Regimen in Breast Cancer Patients With Metabolic-risk Factors: A Randomized, Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Complete response during the delayed phase chemotherapy-Induced Nausea and Vomiting (CINV)
研究概览
简要总结
The aim of THE STUDY to determine whether an olanzapine-based dexamethasone-sparing antiemetic regimen is non-inferior to the standard dexamethasone-containing regimen in preventing delayed-phase Chemotherapy-induced nausea and vomiting while reducing metabolic toxicity in breast cancer patients with metabolic risk factors.
详细描述
Chemotherapy-induced nausea and vomiting remains one of the most distressing and feared adverse effects of anticancer therapy, particularly among patients receiving highly emetogenic chemotherapy regimens such as anthracycline-cyclophosphamide (AC). Despite substantial advances in antiemetic prophylaxis, delayed-phase nausea and vomiting continue to affect a significant proportion of patients, leading to impaired quality of life, poor nutritional intake, treatment non-adherence, and increased healthcare utilization. Chemotherapy-induced nausea and vomiting is typically categorized into acute (within 24 hours), delayed (24-120 hours), anticipatory, breakthrough, and refractory phases. Among these, delayed chemotherapy-induced nausea and vomiting is more difficult to control and often persist despite adherence to guideline-recommended antiemetic regimens. The pathophysiology of delayed chemotherapy-induced nausea and vomiting involves complex interactions between central neurotransmitter pathways, including substance P acting on neurokinin-1 (NK-1) receptors, dopamine, serotonin, and histamine signaling pathways. Consequently, optimal prevention strategies require multi-receptor targeting.
Standard antiemetic regimens for highly emetogenic chemotherapy include a combination of a serotonin (5-HT3) receptor antagonist, an NK-1 receptor antagonist, and dexamethasone. Corticosteroids play a critical synergistic role in enhancing antiemetic efficacy through poorly understood mechanisms that may involve prostaglandin inhibition, blood-brain barrier modulation, and reduced inflammation. However, prolonged corticosteroid use is associated with a wide spectrum of adverse metabolic and systemic effects.
Dexamethasone-induced metabolic toxicity includes hyperglycemia, insulin resistance, fluid retention, hypertension, muscle catabolism, immune suppression, and neuropsychiatric disturbances such as insomnia and mood alterations. These adverse effects are particularly concerning in patients with pre-existing metabolic vulnerabilities, including diabetes mellitus, obesity, metabolic syndrome, and impaired glucose tolerance. Even short-term corticosteroid exposure may precipitate significant glycemic excursions in high-risk populations.
Breast cancer patients frequently present with metabolic risk factors, including obesity, insulin resistance, and dyslipidemia, which may be exacerbated by cancer therapy and supportive medications.
Recent research has focused on corticosteroid-sparing strategies that maintain antiemetic efficacy while minimizing metabolic complications. Olanzapine, an atypical antipsychotic with potent antagonistic effects at dopamine (D2), serotonin (5-HT2 and 5-HT3), histamine (H1), and muscarinic receptors, has emerged as an effective agent in the prevention of both acute and delayed CINV. Its broad receptor activity allows it to target multiple emetogenic pathways simultaneously.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Female patients ≥18 years.
- •Stage I-III breast cancer.
- •Scheduled to receive AC chemotherapy.
- •Presence of metabolic risk factors (diabetes, prediabetes, obesity, metabolic syndrome).
- •ECOG performance status ≤2.
排除标准
- •Recent systemic corticosteroid use.
- •Active nausea or vomiting before chemotherapy.
- •Severe renal or hepatic impairment.
- •Uncontrolled diabetes or hypertension.
- •Psychiatric illness affecting adherence.
- •Pregnancy or lactation.
- •Active infections or inflammatory diseases.
- •Participation in another clinical trial
结局指标
主要结局
Complete response during the delayed phase chemotherapy-Induced Nausea and Vomiting (CINV)
时间窗: 24-120 hours after initiation of AC chemotherapy (Day 0)
Proportion of patients with no emetic episodes and no use of rescue antiemetic medication during the delayed phase, comparing the olanzapine-based dexamethasone-sparing regimen (Arm A) to the standard dexamethasone-containing regimen (Arm B).
Total Control during the delayed phase
时间窗: 24-120 hours after initiation of AC chemotherapy (Day 0)
Proportion of patients with no emetic episodes, no use of rescue antiemetic medication, and no nausea during the delayed phase, comparing the two treatment arms.
次要结局
- Change in Fasting Plasma Glucose(Baseline (Day 0), Day 4, and Day 21)
- Change in Insulin Resistance (HOMA-IR)(Baseline (Day 0), Day 4, and Day 21)
- Purine Turnover / Metabolic Marker (Uric Acid) Assessment(Baseline (Day 0), Day 4, and Day 21)
- Incidence of Hyperglycemia(From Baseline (Day 0) through Recovery Phase (Day 21))
- Intermediate Glycemic Control (Serum Fructosamine)(Baseline (Day 0) to Day 21)
- Change in High-Sensitivity C-Reactive Protein (hs-CRP)(Baseline (Day 0), Day 4, and Day 21)
- Serum Electrolyte Fluctuations (Potassium, Sodium, Magnesium)(Baseline (Day 0) to Day 4)
- Severity and Interference of Treatment-Related Symptoms (Modified National Cancer Institute Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events)(Baseline (Day 0), Peak Toxicity (Day 4), and Recovery Phase (Day 21))
- Daily Nausea Severity, Drowsiness, and Sleep Disturbance (MD Anderson Symptom Inventory)(Day 0 as the baseline and Days 1, 2, 3, 4, and 21)
- Response Categorization by Emetic Episode Frequency(From initiation of chemotherapy through 120 hours (Day 5))
- Time to Treatment Failure(From initiation of chemotherapy through 120 hours (Day 5))
- Complete Control (CC)(24 to 120 hours after initiation of AC chemotherapy (Day 0))
研究者
Mohammed Younus Salih
Resident
Alexandria University