Evaluation of the Effect of Rosuvastatin on Cisplatin-induced Nephrotoxicity and Ototoxicity

Phase 2

• Conditions: Cisplatin Adverse Reaction
• Interventions: Drug: Rosuvastatin 10mg

• Registration Number: NCT04817904
• Lead Sponsor: Cairo University

Brief Summary

Cisplatin is an effective anti-cancer drug for the treatment of many solid tumors in humans. Although the clinical response to cisplatin chemotherapy is encouraging, the nephrotoxicity and ototoxicity of the drug makes it difficult to continue its administration in many cases.

Cisplatin nephrotoxicity occurs through several mechanisms, mainly through the transport and accumulation of cisplatin into renal epithelial cells, injury to nuclear and mitochondrial DNA, activation of multiple cell death pathways and initiation of inflammatory response. Accordingly, several experimental strategies were developed to prevent this toxicity. For example, drugs that reduced renal cisplatin accumulation such as organic cation transporter 2 (OCT2) and copper transporter (Ctr1) inhibitors, antioxidants, antiapoptotic and anti-inflammatory agents were investigated. However, many of these drugs interfered with the cytotoxic effects of cisplatin.

Statins are agents used for reducing plasma cholesterol through the inhibition of the enzyme 3- hydroxy-3- methylglutaryl coenzyme A (HMG-CoA) reductase. In addition, statins are also proven to have pleiotropic, non-lipid dependent effects. These effects include anti-inflammatory actions and reduction of oxidative stress. Based on animal studies performed, statins have been shown to reduce the nephrotoxic effects of cisplatin in rats. In addition, ongoing clinical trials are aiming to investigate the role of statins in the protection against the ototoxicity of cisplatin as well. Our aim is to assess the protective effect of statins on cisplatin-induced nephrotoxicity and ototoxicity in humans.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-11-17
• Study First Submitted: 2021-03-21
• Study First Submitted QC: 2021-03-23
• Study First Posted: 2021-03-26
• Status Verified: 2021-07
• Last Update Submitted: 2021-07-26
• Last Update Posted: 2021-07-28
• Primary Completion: 2021-08
• Study Completion: 2021-08

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 65

Inclusion Criteria

• Histologically proven lung and breast cancer patients indicated for cisplatin (4-6 cycles)
• Normal baseline serum creatinine levels
• Normal baseline audiometry
• Age between 18-70 years

Exclusion Criteria

• Patients with more than one type of cancer
• Patients with prior chemotherapy treatment
• Treatment with statins within 12 months before assignment
• Treatment with fibrates within 4 weeks before assignment
• Pregnancy and Lactation
• Abnormal liver function tests or blood count

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Statin-Treated	Rosuvastatin 10mg	This arm will be receiving: * Cisplatin along with conventional nephroprotective interventions (IV hydration with 3 liters with electrolyte replacement administered on the same day of cisplatin) * Rosuvastatin 10 mg/day

Primary Outcome Measures

Name	Time	Method
Incidence of cisplatin-induced nephrotoxicity	4 months	Increase in serum creatinine by ≥0.3 mg/dL or 1.5-2 fold increase from baseline

Secondary Outcome Measures

Name	Time	Method
Incidence of electrolyte imbalance in both arms	4 months	Reduction in magnesium level ˂1.8 mg/dL and potassium level ˂3.5 mmol/L
Difference in sensory-neural hearing impairment in both arms	4 months	Audiometry assessment
Difference in biological research markers between both arms	4 months	Measurement of total antioxidant capacity and malondialdehyde levels

Trial Locations

Locations (1)

Kasr El-Aini Center of Radiation Oncology and Nuclear Medicine; 🇪🇬 Cairo, Egypt