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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: N-Acetyl Cysteine; Drug: Modified FOLFOX-6 regimen; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Tanta, Egypt
    • Tanta University - Faculty of Medicine ,oncology department, Tanta university hospital.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NAC Group; Patients receive modified FOLFOX-6 chemotherapy plus oral N-acetyl cysteine 1200 mg administered 1 hour before oxaliplatin throughout chemotherapy cycles.	Drug: N-Acetyl Cysteine; Oral N-acetyl cysteine 1200 mg administered 1 hour before oxaliplatin throughout chemotherapy cycles.; Drug: Modified FOLFOX-6 regimen; Oxaliplatin 85 mg/m² IV, leucovorin 400 mg/m² IV, followed by 5-fluorouracil bolus and continuous infusion every 2 weeks.
Placebo Comparator: Placebo Group; Patients receive modified FOLFOX-6 chemotherapy plus oral placebo tablets administered 1 hour before oxaliplatin throughout chemotherapy cycles.	Drug: Modified FOLFOX-6 regimen; Oxaliplatin 85 mg/m² IV, leucovorin 400 mg/m² IV, followed by 5-fluorouracil bolus and continuous infusion every 2 weeks.; Drug: Placebo; Oral placebo tablets identical in appearance to N-acetyl cysteine, administered 1 hour before oxaliplatin throughout chemotherapy cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NCI-CTCAE, Version 5, 2017	The CTCAE is an international classification system used to assess and describe adverse events resulting from medical treatments, especially in cancer therapy, chemotherapy, and radiation therapy. It provides standard criteria to grade the severity of each adverse event on a scale from 1 to 5: Grade 1 (Mild): Mild symptoms, no intervention needed. Grade 2 (Moderate): Symptoms require minimal intervention or slightly affect daily activities. Grade 3 (Severe): Symptoms significantly impact daily activities or require medical intervention. Grade 4 (Life-threatening): Life-threatening symptoms requiring urgent intervention. Grade 5 (Death): Death due to the adverse event.	Adverse events will be assessed using NCI-CTCAE v5.0 at baseline (Day 1, prior to Cycle 1) and after Cycle 2 (Day 15) and after Cycle 4 (Day 29). Each chemotherapy cycle lasts 14 days.
FACT/GOG-Ntx-12	The FACT/GOG-Ntx-12 is a patient-reported outcome measure designed to assess chemotherapy-induced neurotoxicity, particularly from drugs such as platinum agents or taxanes. It consists of 12 items evaluating peripheral neuropathy symptoms, including numbness, tingling, pain, weakness in hands or feet, and difficulty with walking or handling objects. Each item is scored on a 0-4 scale (0 = not at all, 4 = very much), providing a total score reflecting the severity of neurotoxicity. It is primarily used to monitor the impact of chemotherapy on neurological function and related quality of life.	Neurotoxicity-related adverse events will be assessed using the FACT/GOG-Ntx-12 at baseline (Day 1, prior to Cycle 1) and after Cycle 2 (Day 15) and after Cycle 4 (Day 29). Each chemotherapy cycle lasts 14 days.
BPI-SF	The BPI-SF (Brief Pain Inventory - Short Form) is a patient-reported questionnaire used to assess pain severity and its impact on daily functioning. It includes questions about the intensity of pain (e.g., worst, least, average, and current pain) and how pain interferes with activities such as walking, work, mood, sleep, and relationships. Each item is rated on a 0-10 numeric scale (0 = no pain / no interference, 10 = worst imaginable pain / complete interference), allowing calculation of overall pain severity and interference scores. It is widely used in cancer patients and other chronic pain conditions to monitor pain and response to treatment.	Pain severity and interference will be assessed using the BPI-SF at baseline (Day 1, prior to Cycle 1) and after Cycle 2 (Day 15) and after Cycle 4 (Day 29). Each chemotherapy cycle lasts 14 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum IL-6 as a marker of inflammation	Serum IL-6 is a pro-inflammatory cytokine commonly used as a biomarker of inflammation. Elevated IL-6 levels indicate activation of inflammatory pathways, which can occur due to cancer, chemotherapy, or other physiological stressors. Measurement of serum IL-6 allows monitoring of systemic inflammatory responses in patients undergoing chemotherapy.	IL-6 will be measured at pre-oxaliplatin infusion (baseline) and after infusion completion (post-dose) on Day 1 of Cycle 1 in both study arms. NAC is administered orally 1 hour before baseline sample in the intervention arm. Each FOLFOX cycle is 14 days.
Serum total anti-oxidant capacity (TAC) as a biomarker of oxidative stress	Serum total antioxidant capacity (TAC) is a biomarker of oxidative stress, reflecting the overall ability of the serum to neutralize free radicals and reactive oxygen species. TAC is used to evaluate oxidative damage and antioxidant defense mechanisms, which can be affected by chemotherapy.	TAC will be measured at pre-oxaliplatin infusion (baseline) and after infusion completion (post-dose) on Day 1 of Cycle 1 in both study arms. NAC is administered orally 1 hour before baseline sample in the intervention arm. Each FOLFOX cycle is 14 days.
Serum neurotensin as a biomarker for neuropathy	Description: Serum neurotensin (NT) is a peptide biomarker used to assess chemotherapy-induced neuropathy. Changes in serum neurotensin levels correlate with peripheral nerve damage and neurotoxic effects caused by chemotherapeutic agents.	NT will be measured at pre-oxaliplatin infusion (baseline) and after infusion completion (post-dose) on Day 1 of Cycle 1 in both study arms. NAC is administered orally 1 hour before baseline sample in the intervention arm. Each FOLFOX cycle is 14 days.

Collaborators and Investigators

• Sponsor: Tanta University
• Investigators: Principal Investigator: Nehal Mohamed Elmashad, Professor, Department of Clinical Oncology ,Tanta University School of Medicine

Publications and helpful links

General Publications

• Bazzano G, D'Elia JA, Olson RE. Monosodium glutamate: feeding of large amounts in man and gerbils. Science. 1970 Sep 18;169(3951):1208-9. doi: 10.1126/science.169.3951.1208.
• Rome RM. Early diagnosis of gynaecological malignancy. Aust Fam Physician. 1983 Nov;12(11):778-82.
• Baidoun F, Elshiwy K, Elkeraie Y, Merjaneh Z, Khoudari G, Sarmini MT, Gad M, Al-Husseini M, Saad A. Colorectal Cancer Epidemiology: Recent Trends and Impact on Outcomes. Curr Drug Targets. 2021;22(9):998-1009. doi: 10.2174/1389450121999201117115717.
• Tardiolo G, Bramanti P, Mazzon E. Overview on oxidative stress and inflammation induced by chemotherapy. International Journal of Molecular Sciences. 2019;20(15):3771.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Actual): January 1, 2026
• Study Completion (Actual): January 1, 2026

Study Registration Dates

• First Submitted: January 13, 2026
• First Submitted That Met QC Criteria: January 28, 2026
• First Posted (Actual): February 5, 2026

Study Record Updates

• Last Update Posted (Actual): February 10, 2026
• Last Update Submitted That Met QC Criteria: February 6, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Colorectal Cancer; N-Acetylcysteine; Oxaliplatin; Peripheral Neuropathy; Oxaliplatin Induced Peripheral Neuropathy
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Site; Neoplasms; Neuromuscular Diseases; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; Peripheral Nervous System Diseases; Amino Acids, Peptides, and Proteins; Sulfur Compounds; Organic Chemicals; Amino Acids; Cysteine; Amino Acids, Sulfur; Acetylcysteine
• Other Study ID Numbers: 36264MS490/1/24

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared. This decision is due to patient privacy and confidentiality concerns, as well as the limited resources available for data sharing in this investigator-initiated study.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No