Evaluation of The Effect of N-AcetylCysteine in The Prevention of Paclitaxel-Induced Peripheral Neuropathy in Cancer Patients
Overview
- Phase
- Phase 1
- Intervention
- Paclitaxel
- Conditions
- Peripheral Neuropathy Due to Chemotherapy
- Sponsor
- Ain Shams University
- Enrollment
- 75
- Locations
- 1
- Primary Endpoint
- Incidence of chemotherapy induced-peripheral neuropathy
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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.
Investigators
Hadeer Gamal Khalefa
pharmacist
Nasser Institute For Research and Treatment
Eligibility Criteria
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.
Arms & Interventions
control
they will receive paclitaxel 80 mg/m2 once per week for 12 weeks only
Intervention: Paclitaxel
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
Intervention: high dose N-acetylcysteine
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
Intervention: Paclitaxel
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.
Intervention: low dose N-acetylcysteine
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.
Intervention: Paclitaxel
Outcomes
Primary Outcomes
Incidence of chemotherapy induced-peripheral neuropathy
Time Frame: up to 12 week
Number of patients reported neuropathy from paclitaxel
Secondary Outcomes
- severity of chemotherapy induced-peripheral neuropathy(at baseline, at the end of 6 cycle and at the end of 12 cycles)
- Adverse effects(at baseline and each cycle up to 12 week)