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

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

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.)

Study Overview

• Status: Unknown
• Conditions: Head and Neck Neoplasms
• Intervention / Treatment: Drug: N-acetylcysteine

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • São Paulo
    • Campinas, São Paulo, Brazil, 13083-888
      • State University of Campinas - UNICAMP, Hospital das Clinicas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 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; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Campinas, Brazil

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Anticipated): December 1, 2016

Study Registration Dates

• First Submitted: September 5, 2014
• First Submitted That Met QC Criteria: September 13, 2014
• First Posted (Estimate): September 16, 2014

Study Record Updates

• Last Update Posted (Estimate): September 16, 2014
• Last Update Submitted That Met QC Criteria: September 13, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: NAC+Cisplatin2014