Al-Tonbary Y, et al. Vitamin E and N-acetylcysteine as antioxidant adjuvant therapy in children with acute lymphoblastic leukemia. Adv Hematol. 2009:689639.
This study evaluated vitamin E and NAC as adjuvant antioxidant therapy for treatment-induced toxicity in a cohort of children aged 2 to 15 years with acute lymphoblastic leukemia. Patients receiving chemo- and radiotherapy were assigned to either adjuvant supplementation with vitamin E and NAC (Group I) or no supplementation (Group II; n=20 each group). Measures included the occurrence of complications, serum glutathione peroxidase (Glu.PX), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNF-alpha) levels, liver enzymes, and bone marrow status. Group I experienced reduced toxicity as demonstrated by significantly increased Glu.Px, and decreased occurrence of toxic hepatitis, hematological complications, and need for blood/platelet transfusions compared with Group II. However, the decreases seen in MDA and TNF-alpha levels were not significant. The authors conclude these results merit further study to assess long-term benefits while incorporating additional parameters to evaluate the relative benefits and risks.
Lin PC, et al. N-acetylcysteine has neuroprotective effects against oxaliplatin-based adjuvant chemotherapy in colon cancer patients: preliminary data. Support Care Cancer. 2006;14:484-7.
This pilot study evaluated the effect of oral NAC on oxaliplatin-induced neuropathy. Fourteen patients with stage III colon cancer and regional lymph node metastases receiving adjuvant biweekly oxaliplatin 85 mg/m2 plus weekly fluorouracil boluses and low-dose leucovorin were randomized to 1200 mg NAC (Arm A, n=5) or placebo (Arm B, n=9). Neurological and electrophysiological evaluations were performed at baseline and after 4, 8, and 12 treatment cycles and treatment-related toxicity was evaluated based on National Cancer Institute criteria. After 4 cycles of chemotherapy, 7 patients in Arm B vs 2 patients Arm A experienced grade 1 neuropathy. After 8 cycles, 5 patients in Arm B experienced grade 2-4 neuropathy vs no patients in Arm A (p=0.038). After 12 cycles, grade 2-4 neuropathy was observed in 8 and 1 patients in Arm B vs Arm A, respectively (p=0.01). No significant electrophysiological changes in Arm A after 4, 8, or 12 cycles of chemotherapy were found. The authors concluded that oral NAC reduces the incidence of oxaliplatin-induced neuropathy in colon cancer patients receiving oxaliplatin-based adjuvant chemotherapy. Larger confirmatory studies are needed.
Baniasadi S, et al. Protective effect of N-acetylcysteine on antituberculosis drug-induced hepatotoxicity. Eur J Gastroenterol Hepatol. 2010 Oct;22(10):1235-8.
This randomized trial investigated the effect of NAC on antituberculosis drug-induced hepatotoxicity in 60 patients with tuberculosis aged 60 years or more. Patients randomized to Group 1 (n=32) received daily doses of isoniazid, rifampicin, pyrazinamide, and ethambutol. Patients assigned to Group II (n=28) were treated with the same regimen, plus 600 mg NAC, orally twice daily. At both the one- and two-week follow-up, mean alanine aminotransferase and aspartate aminotransferase values were significantly higher (p<0.05) in Group I than in Group II. The authors reported that hepatotoxicity was observed in 12 patients (37.5%) in Group I, and in none of the patients in Group II.
Stav D and Raz M. Effect of N-acetylcysteine on air trapping in COPD: a randomized placebo-controlled study. Chest. 2009 Aug;136(2):381-6.
This randomized, double-blind, cross-over study enrolled patients (n=24) with a diagnosis of COPD aged 40 and older. Enrollment criteria required that patients have a forced expiratory volume in 1 second (FEV1) < 70% of predicted, FEV1/FVC ratio < 0.70, and a functional residual capacity > 120% of predicted normal. Patients were randomized to receive either 1200 mg/day (600 mg twice daily) NAC or placebo treatment for six weeks. This phase was followed by a 2-week washout period and then 6 weeks therapy with the alternate treatment. This study found that the COPD patients had better endurance (p<0.001), inspiratory capacity (p<0.0033), and forced vital capacity (p<0.0029), particularly after exercise, after NAC treatment compared with placebo. The authors concluded that NAC treatment of patients with moderate-to-severe COPD has a beneficial effect on physical performance, probably due to a reduction in air trapping.
Decramer M, et al. Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (Bronchitis Randomized on NAC Cost-Utility Study, BRONCUS): a randomised placebo-controlled trial. Lancet. 2005;365(9470):1552-60.
This 50-center randomized double-blind placebo-controlled trial assigned 523 patients with COPD to NAC 600 mg daily or placebo. Patients were followed for 3 years to measure the primary endpoints of yearly reduction in FEV1 and the number of exacerbations annually; secondary endpoints included quality of life measures. Annual FEV1 decline did not differ between NAC and placebo groups and no difference was seen in subgroup analyses. The number of yearly exacerbations also did not differ between groups, although a subgroup analysis suggested that the exacerbation rate might be reduced with NAC in patients not treated with inhaled corticosteroids and a secondary analysis suggested an effect on hyperinflation. The investigators concluded that NAC was ineffective at preventing lung function deterioration or exacerbations in patients with COPD.
Van Schooten FJ, et al. Effects of oral administration of N-acetyl-L-cysteine: a multi-biomarker study in smokers. Cancer Epidemiol Biomarkers Prev. 2002;11:167-75.
A double-blind, controlled evaluation of NAC supplementation (n=21) versus placebo (n=20) in healthy smokers. Internal dose markers (plasma and BAL fluid cotinine, and urine mutagenicity), biologically effective dose markers (smoking-related DNA adducts, oxidative DNA damage and Hb adducts), and biological response markers (frequency of micronuclei and antioxidants scavenging capacity) were assessed pre- and post-intervention. Patients were randomized to receive 600 mg NAC twice daily or placebo for 6 months. NAC administration significantly inhibited formation of lipophilic-DNA adducts and 8-OH-dG adducts in BAL cells, but had no effect on MFC/BMC PAH-DNA adducts, PBL lipophilic-DNA adducts, and 4-ABP-Hb adducts. Further studies, possibly with development of lung cancer as an outcome, should be conducted.
Van Zandwijk N, et al. EUROSCAN, a randomized trial of vitamin A and N-acetylcysteine in patients with head and neck cancer or lung cancer. J Nat Can Inst. 2000;92:977-86.
A prospective, open-label, randomized evaluation of vitamin A (300,000 IU daily for 1 year followed by 150,000 IU daily for 1 year), N-acetylcysteine (NAC, 600 mg once daily for 2 years), both agents, or placebo in patients with non-small-cell lung cancer (NSCLC), laryngeal cancer, or cancer of the oral cavity. A total of 2,573 patients were randomized to vitamin A (n=647), NAC (n=642), both agents (n=643), or placebo (n=641). Demographics appear similar between treatment arms, but no statistical tests were reported. Five-year survival, event-free survival, and development of secondary tumors were not significantly different between treatment arms. Nearly 18% of patients receiving NAC alone reported adverse occurrences related to gastric events and skin rash. The authors conclude that vitamin A alone, in combination with NAC, or NAC alone is no better than placebo in improving survival or decreasing second tumors for patients with primary NSCLC or head and neck cancers.