Cisplatin Adverse Reaction, Upper GI Cancer
Conditions
Keywords
cisplatin, nephrotoxicity, antioxidant, urine neutrophil gelatinase-associated lipocalin (NGAL)
Brief summary
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.
Detailed description
This study will look for possible protective effects silymarin on kidney injury in patients receiving cisplatin.
Interventions
DRUGSilymarin
Silymarin 420 mg in 3 divided dose plus standard chemotherapy
DRUGPlacebo
placebo tablets: 420 mg in 3 divided dose
DRUGchemotherapy
All patients will receive standard chemotherapy: cisplatin 50-60mg/m2 + fluorouracil 750 mg/m2 + docetaxel 60-80 mg/m2
Sponsors
Tehran University of Medical Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urine concentration of NGAL | up to 9 weeks | All subject receive silymarin at dose of 420mg or placebo in three dose for 65 consecutive day, urine NGAL concentration will be measured. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in VEGF Serum concentration | up to 9 weeks | To assess interaction between silymarin and cancer chemotherapy serum vascular endothelial growth factor will be measured. |
| Tissue activity of caspase 3 | up to 9 weeks | To assess interaction between silymarin and cancer chemotherapy Tissue activity of caspase 3will be measured. |
Countries
Iran
Outcome results
None listed