THE USE OF N-ACETYLCYSTEINE ATTENUATING CISPLATIN-INDUCED TOXICITIES BY OXIDATIVE STRESS

Study Overview
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Brief Summary
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Head and neck cancer corresponds to tumors located in the upper aerodigestive tract, such as the oral cavity, pharynx and larynx. The most effective treatment consists of high dose of cisplatin chemotherapy and radiotherapy, however, their use is limited due to toxicities caused mainly by oxidative stress. The objective of this study will be evaluate the use of n-acetylcysteine attenuating cisplatin-induced toxicities by oxidative stress in head and neck cancer patients. This is a randomized double-blind placebo-controlled clinical trial with consecutive sampling that will be conducted at Oncology Department of Clinic Hospital / University of Campinas (UNICAMP). Head and neck cancer patients who will begin cisplatin antineoplastic treatment (80-100mg/m2 on days 1, 22 and 43) and concurrent radiotherapy will be included in this research. They will be studied in 2 groups (n-acetylcysteine and placebo). All patients will be evaluated in relation to cisplatin induced hematologic and gastrointestinal disorders, nephrotoxicity, ototoxicity, and hepatotoxicity; plasmatic and cellular oxidative stress; quality of life; and pharmacoeconomic evaluation. Results will be statistically analysed using Chi-square, Fisher, Mann-Whitney, and ANOVA for repeated measures tests (p<0.05.)

Official Title
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EVALUATION OF THE USE OF N-ACETYLCYSTEINE ATTENUATING CISPLATIN-INDUCED TOXICITIES BY OXIDATIVE STRESS IN HEAD AND NECK CANCER PATIENTS

Conditions
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Head and Neck Neoplasms

Intervention / Treatment
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* Drug: N-acetylcysteine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: head and neck cancer anticancer treatment - cisplatin (80 to 100 mg/m²) plus radiotherapy patients without previous treatment of head and neck cancer (surgery, chemotherapy and radiotherapy) Exclusion Criteria: severe psychiatric diseases impossibility of verbal communication without caregivers or companions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>The patients will be treated with placebo as follows: 15 mL (0 mg of drug), once a day, during 7 days in each cycle (2 days before chemotherapy with cisplatin, on the day of chemotherapy and more 4 days after chemotherapy). | |
| Experimental: N-Acetylcysteine<br>The patients will be treated with n-acetylcysteine as follows: 15 mL (600mg of drug), once a day, during 7 days in each cycle (2 days before chemotherapy with cisplatin, on the day of chemotherapy and more 4 days after chemotherapy). | Drug: N-acetylcysteine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hematologic, Nephro, and Hepato Toxicity - Degree of toxicity by Common Toxicity Criteria for Adverse Effects (CTCAE - version 4.0) | Hematologic - anemia, leukopenia, neutropenia, lymphopenia, thrombocytopenia; Nephrotoxicity - increase of serum creatinine level and reduction of creatinine clearance; Hepatotoxicity - increase of AST, ALT, ALP, GGT, Total Bilirubin levels. The time frame is 120 hours post-dose and 20 days post-dose (each cycle of Chemotherapy) | 120 hours | 
| Gastrointestinal Toxicity - Degree of toxicity by CTCAE (version 4.0) | Nausea, Vomiting and Diarrhea The time frame is on day 1 and up to 120 hours post-dose (each cycle) | 1 day | 
| audiometric testing | audiometric testing for identification of ototoxic hearing loss. The time frame is prior to day 1 and 30 days after treatment completion | 1 day | 
| Nephrotoxicity | The nephrotoxicity will be evaluated by EDTA-51Cr. The time frame are prior to day 1 and 30 days after treatment completion | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life | Quality of Life by EORTC-QLQ- 30 and EORTC-QLQ-H&N35 questionnaires The time frame are Day, 1, 22, 43, and 21 days after treatment completion | 21 days | 
| Cellular and plasma oxidative stress biomarkers | Time frame are Before day 1; 120 hours post-dose and 20 days post-dose (each cycle of chemotherapy) | 1 day | 
| Effectiveness of anticancer therapy | The effectiveness of anticancer therapy will be analyzed by Computed Tomography of the head and neck. The time frame are prior to day 1 and 30 days after treatment completion | 1 day |