Protective Effect of N-acetylcysteine on Oxaliplatin-Induced Neuropathy in Colorectal Cancer

The Possible Protective Role of N-Acetylcysteine Against Oxaliplatin-Induced Peripheral Neuropathy in Patients With Colorectal Cancer

This study investigates the possible protective role of N-Acetylcysteine against oxaliplatin-induced peripheral neuropathy in patients with colorectal cancer. The trial aims to evaluate whether N-Acetylcysteine can reduce the incidence and severity of neuropathy during chemotherapy.

Oxaliplatin, a common chemotherapeutic agent for colorectal cancer, often induces peripheral neuropathy, which can significantly affect patients' quality of life and limit treatment effectiveness. The neuropathy is partly caused by nerve inflammation and oxidative stress.

N-Acetylcysteine (NAC), an antioxidant, has been suggested to protect neurons from oxidative damage and reduce inflammation.

This interventional, randomized, parallel-assignment study will enroll colorectal cancer patients receiving oxaliplatin-based chemotherapy. Participants will be assigned to either receive N-Acetylcysteine alongside chemotherapy or chemotherapy alone. Primary outcomes include the incidence and severity of peripheral neuropathy measured at predefined intervals during treatment.

Secondary outcomes include biochemical markers of nerve inflammation and oxidative stress, including:

• Neurotensin (marker of nerve inflammation)
• Interleukin-6 (marker of systemic inflammation)
• Total Antioxidant Capacity (marker of oxidative stress)

The study aims to provide evidence on whether N-Acetylcysteine can serve as a protective agent against chemotherapy-induced neuropathy, potentially improving treatment tolerance and patient outcomes.

Inclusion Criteria:

• Males and females aged ≥ 18 years old.

• Patients with histologically confirmed diagnosis of Stage III colorectal cancer and high risk Stage II.

• Patients who will be scheduled to receive modified FOLFOX-6.

• Patients with no contraindication to chemotherapy.

• Adequate baseline hematologic values (absolute neutrophilic 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 (ClCr) ˃ 45 mL/min).

• Patients with adequate liver function (serum bilirubin < 1.5 mg/dl).

• Patients with performance status 0-1 according to Eastern Cooperative Oncology Group (ECOG) score.

Exclusion Criteria:

• Children < 18 years old.
• Prior exposure to chemotherapy.
• Patients with diabetes and other conditions that predispose to neuropathy.
• History of known allergy to oxaliplatin or other platinum agents.
• Concomitant use of any drug has anti-oxidant activity or neuroprotective agent.
• Patients take any medication that increase acetyle choline either central or peripheral.
• Patient was any cardiac disease.
• Pregnant and breastfeeding women.