Evaluation of Effects of Silymarin on Cisplatin Induced Nephrotoxicity in Upper Gastrointestinal Adenocarcinoma

Tehran University of Medical Sciences

Status and phase: Completed; Phase 3; Phase 2

Conditions: Cisplatin Adverse Reaction; Upper GI Cancer

Treatments: Drug: Silymarin; Drug: chemotherapy; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT01829178

91-03-33-18878

Details and patient eligibility

About

Cisplatin is a potent chemotherapeutic agent that has been widely used to treat many solid tumours. acute renal failure, despite conservative fluid and electrolyte management, frequently reported adverse event and limiting cisplatin use. Silymarin, a flavonolignan complex isolated from Silybum marianum, has a strong antioxidant, hepatoprotective, anticancer and in animal model nephroprotective properties. Neutrophil gelatinase-associated lipocalin (NGAL) protein is a promising biomarker to detect acute kidney injury due to cisplatin. Milk thistle extract inhibitory effects on epidermal growth factor receptor, vascular endothelial growth factor and insulin-like growth factor-I have shown in the previous in-vitro studies.The aim of present study,a randomized double-blind placebo- controlled clinical trial, to investigate the therapeutic effect of silymarin on cisplatin induced nephrotoxicity and it's impact on chemotherapy. Fifty-eight patients with diagnosed upper gastrointestinal tract carcinomas randomized to silymarin (420mg) or placebo plus chemotherapy [cisplatin 50-60 mg/m2, 5-fluorouracil mg/m2, docetaxel 60-80 mg/m2 every 21 days] for 63 day after inclusion. serum creatinin, blood urea nitrogen (BUN), serum and urine electrolyte will be measured daily during chemotherapy.

changes in urine NGAL, serum vascular endothelial growth factor (VEGF)and caspase activity assessed up to 64 days.

Full description

This study will look for possible protective effects silymarin on kidney injury in patients receiving cisplatin.

Enrollment: 30 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• age>18 years
• diagnosed
• measurable upper gastrointestinal adenocarcinoma
• swallow problem
• would like to participate in the study
• Glomerular filtration rate(GFR)>45ml/min/1.73m2

Exclusion criteria

• end stage renal disease
• requiring dialysis
• post transplantation
• receiving contrast media during last 72 hours
• chronic use of corticosteroids
• chronic use of angiotensin-converting enzyme inhibitor(ACEI )
• untreated hypo-and hyperthyroidism
• ejection fraction<60%
• active urinary tract infection
• iver disease ( five fold increase of liver enzyme in asymptomatic or 3 fold increase in symptomatic
• use of other nephrotoxic agents such as aminoglycoside, amphotericin
• karnofsky performance status <70

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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30 participants in 2 patient groups, including a placebo group

Control arm

Placebo Comparator group

Description:

Placebo 420 mg daily in three divided doses for 65 days as control along with \[cisplatin 50-60mg/m2 + fluorouracil 750 mg/m2 +docetaxel 60-80 mg/m2\]

Treatment:

Drug: Placebo

Drug: chemotherapy

Exprimental: Silymarin and chemotherapy

Active Comparator group

Description:

silymarin 420 mg daily in three divided doses for 65 days along with standard chemotherapy \[cisplatin 50-60mg/m2 + fluorouracil 750 mg/m2 +docetaxel 60-80 mg/m2 control

Treatment:

Drug: chemotherapy

Drug: Silymarin