6th World Pharmacists & Clinical Pharmacy Annual Congress
Chicago, USA
Marilia B Visacri
University of Campinas, Brazil
Title: Low-dose oral acetylcysteine in the attenuation of cisplatin-induced nephrotoxicity: A randomized double-blind placebo-controlled pilot trial in patients with head and neck cancer
Biography
Biography: Marilia B Visacri
Abstract
Statement of the Problem: Cisplatin chemotherapy induces oxidative stress and therefore has consequent toxicities. The main dose-limiting side effect of cisplatin is nephrotoxicity. The protective antioxidant role of acetylcysteine (NAC) on nephrotoxicity 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 low-dose oral NAC on cisplatin-induced nephrotoxicity in patients with head and neck cancer.
Methodology & Theoretical Orientation: This is a randomized double-blind placebo-controlled pilot trial conducted with 57 patients undergoing treatment with at least one of the three cycles of high-dose cisplatin chemotherapy, concomitant to radiotherapy. Patients were randomly assigned and were given: (1) NAC 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 (2) Placebo, administered similarly to NAC, n=29. Plasma levels of creatinine were monitored to assess nephrotoxicity. Creatinine clearance was estimated using the Cockroft-Gault formula. Severity was classified by Common Toxicity Criteria for Adverse Events (version 4, grade 0 to 4).
Findings: Patients from both groups had similar demographics and clinical characteristics (p>0.05). Throughout the treatment, elevated creatinine was observed in 55.2% of patients in placebo group (grade 1+2: 34.5%; grade 3: 20.7%) and 64.3% in NAC group (grade 1+2: 46.4%; grade 3: 17.9%) [Chi-square test, p=0.6517]. Moreover, reduced creatinine clearance was observed in 96.6% of patients in placebo group (grade 1+2: 75.9%; grade 3+4: 20.7%) and 96.4% in NAC group (grade 1+2: 82.1%; grade 3+4: 14.3%) [Fisher's exact test, p=0.8620].
Conclusion & Significance: Low-dose oral NAC did not attenuate cisplatin-induced nephrotoxicity. Further studies should be conducted to test other oral doses of NAC.