Evaluation of the Effect of N-acetylcysteine in Preventing Cisplatin-Induced Toxicities in Cancer Patients
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- The occurrence of cisplatin-induced ototoxicity in the form of hearing loss.
研究概览
简要总结
Evaluation of the Effect of N-acetylcysteine in Preventing Cisplatin-Induced Toxicities in Cancer Patients
详细描述
Cisplatin is a clinically advanced and highly effective anticancer drug used in the treatment of a wide variety of malignancies, Cisplatin was the first heavy metal compound to be used as an antineoplastic, and since its approval by the FDA in 1978, it is one of the most widely used agents in cancer therapy .
It has been used, sole or combined with other chemotherapeutic agents or even in combination with radiotherapy, in the treatment of several types of cancer, such as cancer of the testicles, ovarian, bladder, lung, head and neck, pancreas, breast, endometrium, esophagus, advanced cervical cancer, lymphomas, metastatic osteosarcomas and melanomas.
The therapeutic effect of cisplatin is significantly increased with dose-escalating, but high-dose therapy is limited by severe toxicities, with nephrotoxicity, neurotoxicity, and ototoxicity being the most important complications. In the case of nephrotoxicity, preventive measures such as saline hydration and osmotic diuresis are employed in clinical practice with minor success.
N-acetylcysteine (NAC) is a thiolic amino acid that has been reported to scavenge free radicals, replenish reduced glutathione (GSH), prevent its depletion, and inhibit lipid peroxidation (LPO). It can also restore the deterioration in the pro-oxidant/antioxidant balance via its metal-chelation activity.
Previous studies suggest that pre-administration of NAC attenuates carboplatin-induced injury in the cochlea of rats. As a GSH prodrug and antioxidant, NAC may ameliorate cochlear damage through a variety of mechanisms, such as providing a substrate for cochlear GSH synthesis, free radical scavenging, and inhibition of cell death pathway activation and necrosis.
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
- None
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
- •Patients are eligible for inclusion if they meet the following criteria:
- •Cancer patients aged >18 years receiving cisplatin-containing chemotherapy.
- •A cisplatin dose starting from 75 mg/m
- •Various cancer types.
- •Both males and females.
- •No history of organ transplantation or kidney dialysis.
- •Eastern cooperative oncology group performance (ECOG):0-2
排除标准
- •Patients with peripheral neuropathy.
- •Preexisting unilateral or bilateral moderate to severe sensorineural hearing loss
- •Patients with speech discrimination affection or those who are unable to participate in audiologic evaluation
- •Co-administration of ifosfamide with cisplatin, because of the known risk of nephrotoxicity.
- •Pregnancy or lactation.
- •Infection with the human immunodeficiency virus (HIV).
- •Prior administration of cisplatin.
- •Intraperitoneal chemotherapy.
- •Inadequate liver function (bilirubin > 1.5 times upper normal limit [ULN] and alanine transaminase [ALT] or aspartate transaminase [AST] > 3 times the upper normal limit [ULN] or up to 5.0 upper normal limit [ULN] in the presence of hepatic metastases).
- •Inadequate renal function (creatinine > 1.25 times upper normal limit [ULN], creatinine clearance < 50mL/min).
- •Serious comorbid systemic disorder incompatible with the study (uncontrolled diabetes mellitus or hypertension, myocardial infarction within the last 6 months).
- •Patients diagnosed with kidney cancer.
- •Exposure to any nephrotoxic drugs or agents.
研究组 & 干预措施
treatment group
b. Group 2 (N = 30 patients) will receive N-acetylcysteine 600 mg twice daily (Acetylcystein ® 600 mg effervescent instant granules sachets, Sedico, Egypt) with cisplatin chemotherapy for 4 cycles (21-28 days and or fractionated)
干预措施: N acetyl cysteine (Drug)
结局指标
主要结局
The occurrence of cisplatin-induced ototoxicity in the form of hearing loss.
时间窗: 4 cycles of cisplatin (at base line and each cycle range from 21-28 days and or fractionated)
hearing loss will be assessed using audiometry
次要结局
- The occurrence of cisplatin-induced nephrotoxicity.(4 cycles of cisplatin (at base line and each cycle range from 21-28 days and or fractionated))
- The occurrence of cisplatin-induced peripheral neuropathy.(4 cycles of cisplatin (at base line and each cycle range from 21-28 days and or fractionated))
研究者
Mahmoud Ibrahim
clinical pharmacist at ain shams university hospitals
Ain Shams University