N-acetyl Cysteine Effect in Peripheral Neuropathy in Cancer Patients

Phase 1

Completed

Interventions: Dietary Supplement: low dose N-acetylcysteine
Dietary Supplement: high dose N-acetylcysteine
Drug: Paclitaxel

Brief Summary: 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: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
low dose N-acetyl cysteine	low dose N-acetylcysteine	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.
high dose N-acetyl cysteine	high dose N-acetylcysteine	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
control	Paclitaxel	they will receive paclitaxel 80 mg/m2 once per week for 12 weeks only
low dose N-acetyl cysteine	Paclitaxel	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.
high dose N-acetyl cysteine	Paclitaxel	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

Primary Outcome Measures

Name	Time	Method
Incidence of chemotherapy induced-peripheral neuropathy	up to 12 week	Number of patients reported neuropathy from paclitaxel

Secondary Outcome Measures

Name	Time	Method
severity of chemotherapy induced-peripheral neuropathy	at baseline, at the end of 6 cycle and at the end of 12 cycles	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.
Adverse effects	at baseline and each cycle up to 12 week	any adverse/ side effect will be evaluated