Evaluation of the use of acetylcysteine attenuating cisplatin-induced toxicities in patients with head and neck cancer undergoing chemotherapy and radiotherapy treatment: influence of oxidative stress

Author(s)

Marília Berlofa Visacri

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
• Defense date: 2017-07-26

Examining board members

Patricia Moriel; Gustavo Jacob Lourenço; Sisi Marcondes; Luis Antonio Salazar Navarrete; Adriano Max Moreira Reis

• Advisor: Carmen Silvia Passos Lima; Patricia Moriel

Abstract

The head and neck cancer represents the fifth most common cancer worldwide. The best treatment for advanced stages is cisplatin chemotherapy with concomitant radiotherapy. Cisplatin is known for its high toxicity and one of the proposed mechanisms is oxidative stress. The protective antioxidant role of acetylcysteine on toxicities due to cisplatin has been reported in experimental models; however, its efficacy in patients has not been elucidated. The aim of this study was to evaluate the possible protective effect of acetylcysteine on cisplatin-induced toxicities in patients with head and neck cancer. This is a randomized double-blind placebo-controlled trial conducted with 57 patients undergoing treatment with high-dose cisplatin chemotherapy, concomitant to radiotherapy. Patients were randomly assigned and were given: (a) acetylcysteine syrup, 600 mg orally once a day at night for 7 consecutive days (two days before the chemotherapy, on the day of chemotherapy, and 4 days after chemotherapy), n = 28; or (b) placebo, administered similarly to acetylcysteine, n = 29. Renal, auditory, hepatic, hematologic, and gastrointestinal toxicities were evaluated. Severity was classified according to the Common Toxicity Criteria for Adverse Events (version 4, grade 0 to 4). Clinical response to cancer treatment, quality of life, cellular and plasmatic oxidative stress were also analyzed. A high prevalence of most toxicities was observed after cisplatin chemotherapy; however, the parameters were similar between the groups. There was a predominance of partial response to treatment. Patients from both groups presented the same pattern of quality of life. In the cellular and plasmatic oxidative stress analysis, minor differences were observed. Overall, there was no statistically significant difference between groups for all outcomes. In conclusion, acetylcysteine did not attenuate cisplatin-induced toxicities, cellular and plasmatic oxidative stress, and did not change the quality of life and clinical response. Further studies should be conducted to test other doses and route of administration of acetylcysteine as well as the interval between administration of cisplatin-acetylcysteine in patients (AU)

• FAPESP's process: 14/04744-7 - Evaluation of the use of N-acetylcysteine attenuating cisplatin-induced toxicities by oxidative stress in head and neck cancer patients
• Grantee: Marília Berlofa Visacri
• Support Opportunities: Scholarships in Brazil - Doctorate