Abstract
Backgrounds and purpose
Radiation therapy is an important mode of treatment for patients with head and neck cancers, but some associated complications can reduce the quality of life. We investigated whether N-acetylcysteine inhalation therapy improved the quality of life of such patients.
Materials and methods
We designed a prospective, non-randomized controlled multi-center study involving 10 institutions. We enrolled 120 patients (80 in the experimental group and 40 in the control group). Patients in the experimental group inhaled nebulized liquid N-acetylcysteine (2400 mg daily) for 8 weeks from the start of radiation therapy. Quality of life was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire H&N 35.
Results
N-acetylcysteine inhalation was not associated with any side effect or discomfort. The reduction in painkiller use from the end of N-acetylcysteine inhalation therapy to the 1-month follow-up was greater in the experimental group than in the control group (P = 0.014). Dry mouth symptoms also improved significantly in the experimental group (P = 0.019).
Conclusion
N-acetylcysteine inhalation improves the quality of life of patients with head and neck cancers who are receiving radiation therapy, without any specific side effect.
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Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
References
Aihara M, Dobashi K, Akiyama M, Naruse I, Nakazawa T, Mori M (2000) Effects of N-acetylcysteine and ambroxol on the production of IL-12 and IL-10 in human alveolar macrophages. Respiration 67:662–671. https://doi.org/10.1159/000056297
Barber C, Powell R, Ellis A, Hewett J (2007) Comparing pain control and ability to eat and drink with standard therapy vs Gelclair: a preliminary, double centre, randomised controlled trial on patients with radiotherapy-induced oral mucositis. Support Care Cancer 15:427–440. https://doi.org/10.1007/s00520-006-0171-1
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424. https://doi.org/10.3322/caac.21492
Chambers MS, Welsh DV, Scrimger RA, Zehn W, Epstein JB, Troha J, Sonis ST (2006) RK-0202 for radiation-induced oral mucositis. J Clin Oncol 24:5523
Colevas AD et al (2018) NCCN guidelines insights: head and neck cancers, version 1.2018. J Natl Compr Canc Netw 16:479–490. https://doi.org/10.6004/jnccn.2018.0026
Demirel C, Kilciksiz S, Evirgen-Ayhan S, Gurgul S, Erdal N (2010) The preventive effect of N-acetylcysteine on radiation-induced dermatitis in a rat model. J BUON 15:577–582
Demirel C, Kilciksiz S, Gurgul S, Erdal N, Yildiz A (2011) N-acetylcysteine ameliorates gamma-radiation-induced deterioration of bone quality in the rat femur. J Int Med Res 39:2393–2401. https://doi.org/10.1177/147323001103900640
Elbini Dhouib I, Jallouli M, Annabi A, Gharbi N, Elfazaa S, Lasram MM (2016) A minireview on N-acetylcysteine: an old drug with new approaches. Life Sci 151:359–363. https://doi.org/10.1016/j.lfs.2016.03.003
Elting LS, Cooksley CD, Chambers MS, Garden AS (2007) Risk, outcomes, and costs of radiation-induced oral mucositis among patients with head-and-neck malignancies. Int J Radiat Oncol Biol Phys 68:1110–1120. https://doi.org/10.1016/j.ijrobp.2007.01.053
Global Burden of Disease Cancer C et al (2017) Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the global burden of disease study. JAMA Oncol 3:524–548. https://doi.org/10.1001/jamaoncol.2016.5688
Gosset P, Wallaert B, Tonnel AB, Fourneau C (1999) Thiol regulation of the production of TNF-alpha, IL-6 and IL-8 by human alveolar macrophages. Eur Respir J 14:98–105. https://doi.org/10.1034/j.1399-3003.1999.14a17.x
He D, Behar S, Roberts JE, Lim HW (1996) The effect of l-cysteine and N-acetylcysteine on porphyrin/heme biosynthetic pathway in cells treated with 5-aminolevulinic acid and exposed to radiation. Photodermatol Photoimmunol Photomed 12:194–199. https://doi.org/10.1111/j.1600-0781.1996.tb00199.x
Huang EY et al (2000) Oral glutamine to alleviate radiation-induced oral mucositis: a pilot randomized trial. Int J Radiat Oncol Biol Phys 46:535–539. https://doi.org/10.1016/s0360-3016(99)00402-2
Kilciksiz S, Demirel C, Evirgen Ayhan S, Erdal N, Gurgul S, Tamer L, Ayaz L (2011) N-acetylcysteine ameliorates nitrosative stress on radiation-inducible damage in rat liver. J BUON 16:154–159
Lalla RV, Sonis ST, Peterson DE (2008) Management of oral mucositis in patients who have cancer. Dent Clin North Am 52:61–77. https://doi.org/10.1016/j.cden.2007.10.002(viii)
Langendijk JA, Doornaert P, Verdonck-de Leeuw IM, Leemans CR, Aaronson NK, Slotman BJ (2008) Impact of late treatment-related toxicity on quality of life among patients with head and neck cancer treated with radiotherapy. J Clin Oncol 26:3770–3776. https://doi.org/10.1200/JCO.2007.14.6647
Li YQ, Zhang ZX, Xu YJ, Ni W, Chen SX, Yang Z, Ma D (2006) N-Acetyl-L-cysteine and pyrrolidine dithiocarbamate inhibited nuclear factor-kappaB activation in alveolar macrophages by different mechanisms. Acta Pharmacol Sin 27:339–346. https://doi.org/10.1111/j.1745-7254.2006.00264.x
Maria OM, Eliopoulos N, Muanza T (2017) Radiation-Induced Oral Mucositis. Front Oncol 7:89. https://doi.org/10.3389/fonc.2017.00089
Marur S, Forastiere AA (2016) Head and neck squamous cell carcinoma: update on epidemiology diagnosis, and treatment. Mayo Clin Proc 91:386–396. https://doi.org/10.1016/j.mayocp.2015.12.017
McDermott JD, Bowles DW (2019) Epidemiology of head and neck squamous cell carcinomas: impact on staging and prevention strategies. Curr Treat Options Oncol 20:43. https://doi.org/10.1007/s11864-019-0650-5
Muanza TM et al (2005) Evaluation of radiation-induced oral mucositis by optical coherence tomography. Clin Cancer Res 11:5121–5127. https://doi.org/10.1158/1078-0432.CCR-05-0403
Paintlia MK, Paintlia AS, Contreras MA, Singh I, Singh AK (2008) Lipopolysaccharide-induced peroxisomal dysfunction exacerbates cerebral white matter injury: attenuation by N-acetyl cysteine. Exp Neurol 210:560–576. https://doi.org/10.1016/j.expneurol.2007.12.011
Redding SW (2005) Cancer therapy-related oral mucositis. J Dent Educ 69:919–929
Rothwell BR, Spektor WS (1990) Palliation of radiation-related mucositis. Spec Care Dentist 10:21–25
Sciubba JJ, Goldenberg D (2006) Oral complications of radiotherapy. Lancet Oncol 7:175–183. https://doi.org/10.1016/S1470-2045(06)70580-0
Siegel RL, Miller KD, Jemal A (2019) Cancer statistics, 2019. CA Cancer J Clin 69:7–34. https://doi.org/10.3322/caac.21551
Simard EP, Torre LA, Jemal A (2014) International trends in head and neck cancer incidence rates: differences by country, sex and anatomic site. Oral Oncol 50:387–403. https://doi.org/10.1016/j.oraloncology.2014.01.016
Sio TT et al (2019) N-acetylcysteine rinse for thick secretion and mucositis of head and neck chemoradiotherapy (Alliance MC13C2): a double-blind randomized clinical trial. Mayo Clin Proc 94:1814–1824. https://doi.org/10.1016/j.mayocp.2019.03.031
Sonis ST (2009) Mucositis: the impact, biology and therapeutic opportunities of oral mucositis. Oral Oncol 45:1015–1020. https://doi.org/10.1016/j.oraloncology.2009.08.006
Wang Y, Zhang ZZ, Chen SQ, Zou ZD, Tu XH, Wang L (2010) Protective effect of N-acetylcysteine on the intestinal barrier dysfunction after radiation injury in rats. Zhonghua Wei Chang Wai Ke Za Zhi 13:219–222
Funding
This research was supported by the research fund of Chungnam National University and the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2019R1A2C1084125, 2019R1H1A2079938, 2019R1C1C1006453).
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None of the authors have a relevant financial relationship with a commercial interest.
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Each patient gave written informed consent and the study protocol was approved by the Institutional Review Board of Chungnam National University Hospital (no. CNUH-2017-06-057).
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Won, HR., Lee, G.h., Kim, J.H. et al. Effects of N-acetylcysteine inhalation therapy on the quality of life of patients with head and neck cancer who are receiving radiation therapy: a prospective non-randomized controlled multi-center study. J Cancer Res Clin Oncol 147, 539–547 (2021). https://doi.org/10.1007/s00432-020-03347-y
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DOI: https://doi.org/10.1007/s00432-020-03347-y