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

Cairo University (CU)

Status and phase: Unknown; Phase 2

Conditions: Cisplatin Adverse Reaction

Treatments: Drug: Rosuvastatin 10mg

Study type: Interventional

Funder types: Other

Identifiers

NCT04817904

S-4-2020

Details and patient eligibility

About

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.

Enrollment: 65 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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65 participants in 2 patient groups

Statin-Treated

Experimental group

Description:

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

Treatment:

Drug: Rosuvastatin 10mg

Statin-Free

No Intervention group

Description:

This arm will be receiving: -Cisplatin along with conventional nephroprotective interventions only (IV hydration with 3 liters with electrolyte replacement administered on the same day of cisplatin)