N-acetyl Cysteine Effect in Peripheral Neuropathy in Cancer Patients

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Peripheral Neuropathy Due to Chemotherapy

Intervention / Treatment
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* Dietary Supplement: low dose N-acetylcysteine
* Dietary Supplement: high dose N-acetylcysteine
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients (>18 years old). Breast cancer patients who will receive adjuvant weekly paclitaxel for 12 cycles. ECOG performance status 0-2 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: Patients who have any of the following: Clinical neuropathy. Diabetes mellitus. Patients receiving vitamin B1, B6, B12,or other vitamin supplemental therapy. Patients receiving antidepressants, opioids, adjuvant analgesic agents (eg, anticonvulsants, clonazepam, or mexiletine), topical analgesics, and amifostine. Hypersensitivity to NAC.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: control<br>they will receive paclitaxel 80 mg/m2 once per week for 12 weeks only | Drug: Paclitaxel<br>* Paclitaxel 80mg /m2 IV<br>|
| Experimental: high dose N-acetyl cysteine<br>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 | Dietary Supplement: high dose N-acetylcysteine<br>* N-acetylcysteine 1200mg twice daily<br>Drug: Paclitaxel<br>* Paclitaxel 80mg /m2 IV<br>|
| Experimental: low dose N-acetyl cysteine<br>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. | Dietary Supplement: low dose N-acetylcysteine<br>* N-acetylcysteine 600mg twice daily<br>Drug: Paclitaxel<br>* Paclitaxel 80mg /m2 IV<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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paclitaxel, peripheral neuropathy, N-acetyl cysteine