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Review

Radiotherapy-induced severe oral mucositis: pharmacotherapies in recent and current clinical trials

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Pages 301-310 | Received 20 Dec 2022, Accepted 16 Mar 2023, Published online: 22 Mar 2023

References

  • Sonis ST, Elting LS, Keefe D, et al. Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer. 2004 May 1;100(9 Suppl):1995–2025.
  • Blijlevens N, Schwenkglenks M, Bacon P, et al. Prospective oral mucositis audit: oral mucositis in patients receiving high-dose melphalan or BEAM conditioning chemotherapy–European blood and marrow transplantation mucositis advisory group. J Clin Oncol. 2008 Mar 20;26(9):1519–1525.
  • Rosenthal DI. Consequences of mucositis-induced treatment breaks and dose reductions on head and neck cancer treatment outcomes. J Support Oncol. 2007 Oct;5(9 Suppl 4):23–31.
  • Lalla RV, Brennan MT, Gordon SM, et al. Oral mucositis due to high-dose chemotherapy and/or head and neck radiation therapy. J Natl Cancer Inst Monogr. 2019 Aug 1;2019(53);lgz011.
  • Epstein JB, Stevenson-Moore P. Benzydamine hydrochloride in prevention and management of pain in oral mucositis associated with radiation therapy. Oral Surg Oral Med Oral Pathol. 1986 Aug;62(2):145–148.
  • Nugent M, Bryant V, Butcher C, et al. Photobiomodulation in the management of oral mucositis for adult head and neck cancer patients receiving irradiation: the LiTEFORM RCT. Health Technol Assess. 2022 Dec;26(46):1–172.
  • Barasch A, Peterson DE. Risk factors for ulcerative oral mucositis in cancer patients: unanswered questions. Oral Oncol. 2003 Feb;39(2):91–100.
  • Al-Dasooqi N, Sonis ST, Bowen JM, et al. Emerging evidence on the pathobiology of mucositis. Support Care Cancer. 2013 Jul;21(7):2075–2083.
  • Sonis ST. Pathobiology of oral mucositis: novel insights and opportunities. J Support Oncol. 2007 Oct;5(9 Suppl 4):3–11.
  • Noronha V, Joshi A, Patil VM, et al. Once-a-week versus once-every-3-weeks cisplatin chemoradiation for locally advanced head and neck cancer: a phase III randomized noninferiority trial. J Clin Oncol. 2018 Apr 10;36(11):1064–1072.
  • Caudell JJ, Gillison ML, Maghami E, et al. NCCN guidelines(R) Insights: head and neck cancers, version 1.2022. J Natl Compr Canc Netw. 2022 Mar;20(3):224–234.
  • Villa A, Vollemans M, De Moraes A, et al. Concordance of the WHO, RTOG, and CTCAE v4.0 grading scales for the evaluation of oral mucositis associated with chemoradiation therapy for the treatment of oral and oropharyngeal cancers. Support Care Cancer. 2021 Oct;29(10):6061–6068.
  • World Health Organization. WHO handbook for reporting results of cancer treatment. Geneva: World Health Organization; 1979.
  • Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2022. CA Cancer J Clin. 2022 Jan;72(1):7–33.
  • Murphy CK, Fey EG, Watkins BA, et al. Efficacy of superoxide dismutase mimetic M40403 in attenuating radiation-induced oral mucositis in hamsters. Clin Cancer Res. 2008 Jul 1;14(13):4292–4297.
  • Anderson CM, Sonis ST, Lee CM, et al. Phase 1b/2a trial of the superoxide dismutase mimetic GC4419 to reduce chemoradiotherapy-induced oral mucositis in patients with oral cavity or oropharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2018 Feb 1;100(2):427–435.
  • Anderson CM, Lee CM, Saunders DP, et al. Phase IIb, randomized, double-blind trial of GC4419 versus placebo to reduce severe oral mucositis due to concurrent radiotherapy and cisplatin for head and neck cancer. J Clin Oncol. 2019 Dec 1;37(34):3256–3265.
  • Anderson CM, Lee CM, Kelley JR, et al. ROMAN: phase 3 trial of avasopasem manganese (GC4419) for severe oral mucositis (SOM) in patients receiving chemoradiotherapy (CRT) for locally advanced, nonmetastatic head and neck cancer (LAHNC). J clin oncol. 2022;40(16_suppl): 6005-6005.
  • Anderson CM, Lee CM, Saunders D, et al. Two-year tumor outcomes of a phase 2B, randomized, double-blind trial of avasopasem manganese (GC4419) versus placebo to reduce severe oral mucositis owing to concurrent radiation therapy and cisplatin for head and neck cancer. Int J Radiat Oncol Biol Phys. 2022 Nov 1;114(3):416–421.
  • Steinbach EJ, Monga V, Furqan M, et al. Effects of GC4419 (avasopasem manganese) on chronic kidney disease in head and neck cancer patients treated with radiation and cisplatin. J clin oncol. 2020 May 20;38(15_suppl): 12071-12071.
  • Oronsky B, Goyal S, Kim MM, et al. A review of clinical radioprotection and chemoprotection for oral mucositis. Transl Oncol. 2018 Jun;11(3):771–778.
  • Das DS, Ray A, Das A, et al. A novel hypoxia-selective epigenetic agent RRx-001 triggers apoptosis and overcomes drug resistance in multiple myeloma cells. Leukemia. 2016 Nov;30(11):2187–2197.
  • Ning S, Sekar TV, Scicinski J, et al. Nrf2 activity as a potential biomarker for the pan-epigenetic anticancer agent, RRx-001. Oncotarget. 2015 Aug 28;6(25):21547–21556.
  • Bonomi MR, Blakaj D, Sher D, et al. Phase 2 pilot trial of RRx-001 as an anti-mucositis agent in patients with head and neck cancer treated with chemoradiation (PREVLAR). J clin oncol. 2022;40(16_suppl): 6078-6078. DOI:10.1200/JCO.2022.40.16_suppl.6078.
  • Yu WD, Kim YJ, Cho MJ, et al. MIT-001 restores human placenta-derived mesenchymal stem cells by enhancing mitochondrial quiescence and cytoskeletal organization. Int J Mol Sci. 2021 May 11;22(10). DOI:10.3390/ijms22105062.
  • Min L, Shu-Li Z, Feng Y, et al. NecroX-5 ameliorates bleomycin-induced pulmonary fibrosis via inhibiting NLRP3-mediated epithelial-mesenchymal transition. Respir Res. 2022 May 20;23(1):128.
  • Im KI, Nam YS, Kim N, et al. Regulation of HMGB1 release protects chemoradiotherapy-associated mucositis. Mucosal Immunol. 2019 Sep;12(5):1070–1081.
  • Lee HR, Yoo N, Kim JH, et al. The therapeutic effect of PLAG against oral mucositis in hamster and mouse model. Front Oncol. 2016;6:209.
  • Kim YJ, Shin JM, Shin SH, et al. 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol ameliorates arthritic joints through reducing neutrophil infiltration mediated by IL-6/STAT3 and MIP-2 activation. Oncotarget. 2017 Nov 14;8(57):96636–96648.
  • Jeong J, Kim YJ, Lee DY, et al. 1-Palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) attenuates gemcitabine-induced neutrophil extravasation. Cell Biosci. 2019;9:4.
  • Kim GT, Lee DY, Sohn KY, et al. PLAG enhances macrophage mobility for efferocytosis of active neutrophils via membrane redistribution of P2Y2. Cancer Res. 2019;79(13 Suppl):Abstract nr 4586.
  • Choi S, Shin SH, Lee HR, et al. 1-Palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol ameliorates chemoradiation-induced oral mucositis. Oral Dis. 2020 Jan;26(1):111–121.
  • Henson C, Clayburgh D, Lee AS, et al. Phase 2, randomized, double-blind trial of EC-18 versus placebo to mitigate the development and time course of oral mucositis from concomitant chemoradiation for head and neck cancer. J clin oncol. 2022;40(16_suppl): 12106-12106. DOI:10.1200/JCO.2022.40.16_suppl.12106.
  • Osei-Fofie D, Wetter J, Landers GA, et al. Phase Ib, international, dose-escalation study to evaluate the safety, pharmacokinetics (PK) and efficacy of ST-617 for the attenuation of oral mucositis (OM) in patients receiving chemoradiation (CRT) for head and neck (H&N) cancer. J clin oncol. 2021;39(15_suppl): 6075-6075. DOI:10.1200/JCO.2021.39.15_suppl.6075.
  • Osei-Fofie D, Landers G, Wetter JA, et al. 1846P phase Ib, international, dose-escalation study to evaluate the safety, pharmacokinetics (PK) and efficacy of ST-617 a dithiolethione, for the attenuation of oral mucositis (OM) in patients receiving chemoradiation (CRT) for head & neck (H&N) cancer. Ann Oncol. 2020;31:S1058–S1059.
  • Mitchell JB, DeGraff W, Kaufman D, et al. Inhibition of oxygen-dependent radiation-induced damage by the nitroxide superoxide dismutase mimic, tempol. Arch Biochem Biophys. 1991 Aug 15;289(1):62–70.
  • Ding W, Wang B, Zhang M, et al. Tempol, a superoxide dismutase-mimetic drug, ameliorates progression of renal disease in CKD mice. Cell Physiol Biochem. 2015;36(6):2170–2182.
  • Metz JM, Smith D, Mick R, et al. A phase I study of topical tempol for the prevention of alopecia induced by whole brain radiotherapy. Clin Cancer Res. 2004 Oct 1;10(19):6411–6417.
  • Cotrim AP, Sowers AL, Lodde BM, et al. Kinetics of tempol for prevention of xerostomia following head and neck irradiation in a mouse model. Clin Cancer Res. 2005 Oct 15;11(20):7564–7568.
  • Cotrim AP, Yoshikawa M, Sunshine AN, et al. Pharmacological protection from radiation ± cisplatin-induced oral mucositis. Int J Radiat Oncol Biol Phys. 2012 Jul 15;83(4):1284–1290.
  • Hu L, Wang Y, Cotrim AP, et al. Effect of tempol on the prevention of irradiation-induced mucositis in miniature pigs. Oral Dis. 2017 Sep;23(6):801–808.
  • Giralt J, Tao Y, Kortmann RD, et al. Randomized phase 2 trial of a novel clonidine mucoadhesive buccal tablet for the amelioration of oral mucositis in patients treated with concomitant chemoradiation therapy for head and neck cancer. Int J Radiat Oncol Biol Phys. 2020 Feb 1;106(2):320–328.
  • Peterson DE, Barker NP, Akhmadullina LI, et al. Phase II, randomized, double-blind, placebo-controlled study of recombinant human intestinal trefoil factor oral spray for prevention of oral mucositis in patients with colorectal cancer who are receiving fluorouracil-based chemotherapy. J Clin Oncol. 2009 Sep 10;27(26):4333–4338.
  • Caluwaerts S, Vandenbroucke K, Steidler L, et al. AG013, a mouth rinse formulation of Lactococcus lactis secreting human Trefoil Factor 1, provides a safe and efficacious therapeutic tool for treating oral mucositis. Oral Oncol. 2010 Jul;46(7):564–570.
  • Limaye SA, Haddad RI, Cilli F, et al. Phase 1b, multicenter, single blinded, placebo-controlled, sequential dose escalation study to assess the safety and tolerability of topically applied AG013 in subjects with locally advanced head and neck cancer receiving induction chemotherapy. Cancer. 2013 Dec 15;119(24):4268–4276.
  • Spielberger R, Stiff P, Bensinger W, et al. Palifermin for oral mucositis after intensive therapy for hematologic cancers. N Engl J Med. 2004 Dec 16;351(25):2590–2598.
  • Chang JH, Wu CC, Yuan KS, et al. Locoregionally recurrent head and neck squamous cell carcinoma: incidence, survival, prognostic factors, and treatment outcomes. Oncotarget. 2017 Aug 15;8(33):55600–55612.
  • Sonis ST. New thoughts on the initiation of mucositis. Oral Dis. 2010 Oct;16(7):597–600.

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