N-acetyl Cysteine Effect in Peripheral Neuropathy in Cancer Patients

Ain Shams University

Status and phase: Completed; Phase 2; Phase 1

Conditions: Peripheral Neuropathy Due to Chemotherapy

Treatments: Dietary Supplement: high dose N-acetylcysteine; Dietary Supplement: low dose N-acetylcysteine; Drug: Paclitaxel

Study type: Interventional

Funder types: Other

Identifiers

NCT03492047

PHCL93

Details and patient eligibility

About

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.

Full 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.

Enrollment: 75 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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75 participants in 3 patient groups

control

Active Comparator group

Description:

they will receive paclitaxel 80 mg/m2 once per week for 12 weeks only

Treatment:

Drug: Paclitaxel

high dose N-acetyl cysteine

Experimental group

Description:

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

Treatment:

Dietary Supplement: high dose N-acetylcysteine

Drug: Paclitaxel

low dose N-acetyl cysteine

Experimental group

Description:

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.

Treatment:

Dietary Supplement: low dose N-acetylcysteine

Drug: Paclitaxel