A Randomized Double-blind Study of N-AcetylCysteine vs. Placebo to Prevent Neurotoxicity Induced by Platinum Containing Chemotherapy in Patients Treated for (Non)Small Cell Lung Cancer and Malignant Mesothelioma
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 发起方
- 入组人数
- 69
- 试验地点
- 1
- 主要终点
- The occurrence of peripheral neuropathy: with the peripheral neuropathy score (PNP-score) and the electrophysiological measurements. If no EMG is available, then audiometric measurements will be taken into account.
研究概览
简要总结
In this study we want to investigate the efficacy of N-acetylcysteine (NAC), which is an anti-oxidant, in the prevention of cisplatin-induced neural toxicity, in patients treated for lung cancer with chemotherapy containing cisplatin.
详细描述
Background of the study:
Cisplatin (CDDP) is a major compound in chemotherapy in patients with non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC) and malignant mesothelioma. Cisplatin is associated with a number of side-effects, one of which is neurotoxicity. For a number of patients this neurotoxicity is a dose-limiting side-effect. At this point no measures are taken to prevent the occurrence of neurotoxicity during treatment with cisplatin. Recent studies have shown that the association of anti-oxidants to the treatment with cisplatin has a neuroprotective effect without loss of anti-tumour efficacy of cisplatin. One of these anti-oxidants is glutathione (GSH), this is a natural anti-oxidant that is synthesized in all cells, mainly in the liver and the muscles. This GSH plays a central role in the pathophysiology (of efficacy and of side-effects) of cisplatin. We want to investigate the efficacy of N-acetylcysteine (NAC), which serves as a substrate for the synthesis of GSH, in the prevention of cisplatin-induced neurotoxicity.
Objective of the study:
- The primary objective is to establish the neuroprotective efficacy of NAC against cisplatin-induced neurotoxicity. Mainly the sensory neuronal guidance will be assessed before and after treatment with cisplatin in a group of patients receiving NAC compared to a control-group receiving placebo. If peripheral neuropathy can't be measured, neuropathy will be assessed as ototoxicity through measuring audiograms.
- The secondary objectives are establishing the protective effect of NAC regarding other cisplatin-induced side-effects such as haematological pathology (anaemia, leucopenia, thrombopenia, febrile neutropenia), loss of creatinine clearance and occurrence of liver-chemistry abnormalities. Secondary objectives include also establishing the effect on tumour response, clinical performance (Karnofsky performance index) and quality of life.
Study design:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •diagnose is histologically or cytologically proven (NSCLC,SCLC), malignant mesothelioma (histologically)
- •at least 4 cycles of cisplatin are planned
- •adequate renal function (creatinine clearance as calculated by Cockroft-Gault method > 60 ml/min)
- •Karnofsky performance score > 60 %
- •written informed consent
- •patient must be able to comply with study measurements i.e. hospital visits for EMG and QoL assessments
- •age ≥ 18 years
排除标准
- •patients with pre-existing neuropathy
- •patients not willing to stop earlier prescribed NAC
- •patients not willing to stop vitamins E and A above daily advisory dosage
- •uncontrolled metastasis in the central or peripheral nervous system
研究组 & 干预措施
1
N-Acetylcysteine
干预措施: N-Acetylcysteine (Drug)
2
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
The occurrence of peripheral neuropathy: with the peripheral neuropathy score (PNP-score) and the electrophysiological measurements. If no EMG is available, then audiometric measurements will be taken into account.
时间窗: 5 months
次要结局
- Quality of life(5 months)
- haematological abnormalities(5 months)
- creatinine clearance.(5 months)
- liver chemistry abnormalities(5 months)
- Karnofski Performance Score(5 months)