Neuroprotection of Memantine and Rosuvastatin

Neuroprotective Effect of Memantine and Rosuvastatin Against Oxaliplatin Induced Peripheral Neuropathy in Patients With Colorectal Cancer

Memantine is used to slow the neurotoxicity of Alzheimer disease. Rosuvastatin used as a lipid-lowering agent . Increased bioavailability of endothelial-derived nitric oxide improves endothelium function , increases cerebral blood flow which may all contribute to the neuroprotective effects of rosuvastatin .

The goal of this clinical trial is to prevent oxaliplatin induced peripheral neuropathy in patients with colorectal cancer.The aim of this current study is to assess the neuroprotective effect of memantine and rosuvastatin against oxaliplatin induced peripheral neuropathy.

Memantine treatment ameliorated oxaliplatin-elevated intracellular production of reactive oxygen species and lipid product malondialdehyde expression. Memantine alleviated impairment of the mitochondrial membrane potential and ATP production by oxaliplatin Rosuvastatin decreases axonal injury and cortical thickness. Rosuvastatin attenuated the chronic constriction injury induced neuropathic pain and inflammation .Thus, antinociceptive effects of rosuvastatin might be channeled through inhibition of inflammatory biomarkers and antioxidant properties .

Inclusion criteria

• Age above 18 years old for both gender .
• Adequate baseline hematologic values (absolute neutrophil count ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L and hemoglobin level ≥ 10 g/dl).
• Patients with adequate renal function (serum creatinine < 1.5 mg/dl or creatinine clearance ˃ 45 mL/min).
• Patients with adequate liver function (serum bilirubin < 1.5 mg/dl).
• Patients with performance status <2 according to Eastern Cooperative Oncology Group (ECOG) score.
• Patients who will be scheduled to receive modified FOLFOX-6 or XELOX regimen.
• Patients with histologically confirmed diagnosis of stage III or stage IV colorectal cancer.

Exclusion criteria:

• Children < 18 years old.
• Prior exposure to neurotoxic chemotherapy (oxaliplatin, cisplatin, vincristine, paclitaxel, or docetaxel, INH).
• Patients with diabetes and other conditions that predispose to neuropathy as hypothyroidism, autoimmune diseases, hepatitis C.
• History of known allergy to oxaliplatin or other platinum agents.
• Patients with other inflammatory or stressful conditions.
• Concomitant use of multivitamins (vitamins E, C, A), tricyclic antidepressants, other neuro-protective medications (gabapentin, lamotrigine, carbamazepine and phenytoin).
• Patients on amantadine , acetazolamide, dextromethorphan, aluminum hydroxide magnesium hydroxide and febuxostat .
• Concurrent active cancer originating from a primary site other than colon or rectum.
• Pregnant and breastfeeding women.
• Sever renal insufficiency (creatinine clearance < 25 ml/ minute) .