N-acetyl Cysteine Effect in Peripheral Neuropathy in Cancer Patients

Evaluation of The Effect of N-AcetylCysteine in The Prevention of Paclitaxel-Induced Peripheral Neuropathy in Cancer Patients

The purpose of the study is to evaluate the effect of N-acetyl cysteine in combination with paclitaxel on the clinical outcomes of patients with peripheral neuropathy, paclitaxel-induced peripheral neuropathy affect quality of life in cancer patients.

new therapeutic approches such as the antioxidant N-acetyl cysteine, showed to has neuroprotective effect, the aim of the study is to evaluate the effect of N- acetylcysteine(NAC) administration in the prevention of paclitaxel-Induced peripheral neuropathy.

Study Overview

• Status: Completed
• Conditions: Peripheral Neuropathy Due to Chemotherapy
• Intervention / Treatment: Drug: Paclitaxel; Dietary supplement: high dose N-acetylcysteine; Dietary supplement: low dose N-acetylcysteine

Detailed Description

Paclitaxel is a first-line chemotherapeutic treatment of solid tumors. Neuronal damage also seems to have a major role in paclitaxel-induced neuropathic pain, paclitaxel contributes to ROS formation (superoxide, hydroxyl radical, nitric oxide and hydrogen peroxide) in neuronal mitochondria that are involved in nerve injury-induced.

N-acetylcysteine (NAC) is a cysteine pro-drug and glutathione (GSH) precursor which is a protective agent and detoxifies and scavenges reactive oxygen species (ROS), which seems to help normalize the oxidative status.

It has been reported that high dose of N-acetylcysteine shown to Prevent retrograde motor neuron death after neonatal peripheral nerve injury and significantly increases motor neuron survival, which may improve functional outcomes after obstetrical brachial plexus injury in rats.

Also, it has been reported that NAC significantly inhibited CCI-induced microglia activation but elicited no notable effects on astrocytes. These results demonstrate an effective and safe approach that has been used clinically to alleviate neuropathic pain via the powerful inhibition of the activation of MMPs in rats.

N-acetylcysteine has been shown to have neuroprotective effects against oxaliplatin-based adjuvant chemotherapy in colon cancer patients with Oral administration of N-acetylcysteine1,200 mg) was given one and a half hours before each oxaliplatin administration.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 11566
    • AinShams university hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult patients (>18 years old).
2. Breast cancer patients who will receive adjuvant weekly paclitaxel for 12 cycles.
3. ECOG performance status 0-2
4. Adequate bone marrow function (white blood count ≥4,000/mm3, platelet count ≥100,000/mm3), liver function (serum total bilirubin <1.5 mg/dl), renal function (creatinine <1.5 mg/dl).

Exclusion Criteria:

1. Patients who have any of the following:

   • Clinical neuropathy.
   • Diabetes mellitus.
2. Patients receiving vitamin B1, B6, B12,or other vitamin supplemental therapy.
3. Patients receiving antidepressants, opioids, adjuvant analgesic agents (eg, anticonvulsants, clonazepam, or mexiletine), topical analgesics, and amifostine.
4. Hypersensitivity to NAC.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: control; they will receive paclitaxel 80 mg/m2 once per week for 12 weeks only	Drug: Paclitaxel; Paclitaxel 80mg /m2 IV
Experimental: high dose N-acetyl cysteine; they will receive paclitaxel 80 mg/m2 once per week for 12 weeks and high dose N-acetylcysteine (1200 mg twice daily) for the paclitaxel treatment period	Drug: Paclitaxel; Paclitaxel 80mg /m2 IV; Dietary supplement: high dose N-acetylcysteine; N-acetylcysteine 1200mg twice daily
Experimental: low dose N-acetyl cysteine; they will receive paclitaxel 80 mg/m2 once per week for 12 weeks and low dose N-acetylcysteine (600mg twice daily) for the paclitaxel treatment period.	Drug: Paclitaxel; Paclitaxel 80mg /m2 IV; Dietary supplement: low dose N-acetylcysteine; N-acetylcysteine 600mg twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of chemotherapy induced-peripheral neuropathy	Number of patients reported neuropathy from paclitaxel	up to 12 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
severity of chemotherapy induced-peripheral neuropathy	severity of paclitaxel induced peripheral neuropathy using NCI-CTCAE criteria	at baseline and before each cycle up to 12 week
Adverse effects	any adverse/ side effect will be evaluated	at baseline and each cycle up to 12 week
severity of chemotherapy induced-peripheral neuropathy	severity of chemotherapy induced-peripheral neuropathy using modified total neuropathy score ,Each neuropathy item is scored by a physician on a 0-4 scale the scores are summed to obtain a total score, modified total neuropathy score score ranges from 0-24 with higher total scores indicate more severe neuropathy.	at baseline, at the end of 6 cycle and at the end of 12 cycles

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity(FACT-GOG-NTX) subscale	measures quality of life related to signs and symptoms of paclitaxel induced peripheral neuropathy	weekly up to 12 week
serum nerve growth factor	measuring serum level of nerve growth factor using ELISA KIT	at baseline and after 12 week
serum malionaldehyde	measuring serum level of maliomaldehyde using spectrophometric kit	at baseline and after 12 week

Collaborators and Investigators

• Sponsor: Ain Shams University
• Collaborators: Nasser Institute For Research and Treatment
• Investigators: Principal Investigator: Hadeer G Khalefa, master, Nassar institute for research and treatment hospital

Publications and helpful links

General Publications

• Khalefa HG, Shawki MA, Aboelhassan R, El Wakeel LM. Evaluation of the effect of N-acetylcysteine on the prevention and amelioration of paclitaxel-induced peripheral neuropathy in breast cancer patients: a randomized controlled study. Breast Cancer Res Treat. 2020 Aug;183(1):117-125. doi: 10.1007/s10549-020-05762-8. Epub 2020 Jun 29.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2018
• Primary Completion (Actual): April 1, 2019
• Study Completion (Actual): June 30, 2019

Study Registration Dates

• First Submitted: March 2, 2018
• First Submitted That Met QC Criteria: April 2, 2018
• First Posted (Actual): April 10, 2018

Study Record Updates

• Last Update Posted (Actual): February 27, 2020
• Last Update Submitted That Met QC Criteria: February 25, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: paclitaxel; peripheral neuropathy; N-acetyl cysteine
• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protective Agents; Antineoplastic Agents, Phytogenic; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Paclitaxel; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: PHCL93

Drug and device information, study documents

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