Trotti Andy, Garden Adam, Warde Padraig, Symonds Paul, Langer Corey, Redman Rebecca, Pajak Thomas F, Fleming Tomas R, Henke Michael, Bourhis Jean, Rosenthal David I, Junor Elizabeth, Cmelak Anthony, Sheehan Finbarr, Pulliam Janis, Devitt-Risse Patricia, Fuchs Henry, Chambers Mark, O'Sullivan Brian, Ang K Kian
Radiation Oncology Program, H. Lee Moffitt Cancer Center at the University of South Florida, Tampa, FL, USA.
Int J Radiat Oncol Biol Phys. 2004 Mar 1;58(3):674-81. doi: 10.1016/S0360-3016(03)01627-4.
Oral mucositis (OM) causes significant morbidity during the course of radiotherapy (RT) treatment of head-and-neck cancer. It is hypothesized that infection plays a role in the development of OM. We tested the efficacy of iseganan HCl (iseganan), a synthetic peptide with broad-spectrum antimicrobial activity, for preventing RT-associated OM.
A multinational, randomized, double-blind, controlled trial was performed on patients receiving primary RT, primary chemoradiotherapy or postoperative RT. Patients were randomized to receive iseganan oral solution plus standard-of-care oral hygiene (SOC), placebo plus SOC, or SOC alone throughout the RT administration period. The severity of OM was assessed by NCI-CTC scoring and clinical symptoms by patient questionnaire.
A total of 545 patients were randomized to the study. Nine percent of the patients in both the iseganan and placebo groups did not develop ulcerative OM (Grades 2, 3, 4) (p = 0.998) whereas only 2% of the patients receiving SOC alone remained free of oral ulceration (p = 0.049). The maximum severity of mouth pain and difficulty swallowing did not differ in patients treated with iseganan or placebo. However, patients in both intervention groups reported less mouth pain and difficulty swallowing than did patients receiving SOC alone. Nausea was the only adverse event that occurred with >/=5% increased frequency in the iseganan group than in either the placebo or SOC groups (51% vs. 42% vs. 46%). Adverse events leading to study drug discontinuation and death did not differ significantly between groups.
Iseganan oral solution was safe but did not reduce the risk for developing ulcerative OM relative to placebo. Intensified oral hygiene or the administration of the vehicle used to deliver study drug in this trial appears to have reduced the risk and severity of OM. Our results suggest that antimicrobial intervention may not meaningfully affect the pathogenesis of radiation-induced OM.
口腔黏膜炎（OM）在头颈癌放射治疗（RT）过程中会导致严重的发病率。据推测，感染在OM的发生发展中起作用。我们测试了具有广谱抗菌活性的合成肽盐酸异戈那肽（异戈那肽）预防RT相关OM的疗效。
对接受原发性RT、原发性放化疗或术后RT的患者进行了一项多国、随机、双盲、对照试验。在整个RT给药期间，患者被随机分为接受异戈那肽口服溶液加标准护理口腔卫生（SOC）、安慰剂加SOC或仅接受SOC。通过NCI-CTC评分评估OM的严重程度，并通过患者问卷评估临床症状。
共有545名患者被随机纳入该研究。异戈那肽组和安慰剂组中均有9%的患者未发生溃疡性OM（2级、3级、4级）（p = 0.998），而仅接受SOC的患者中只有2%没有口腔溃疡（p = 0.049）。接受异戈那肽或安慰剂治疗的患者口腔疼痛和吞咽困难的最大严重程度没有差异。然而，两个干预组的患者报告的口腔疼痛和吞咽困难均少于仅接受SOC的患者。恶心是异戈那肽组中发生频率比安慰剂组或SOC组增加≥5%的唯一不良事件（51%对42%对46%）。导致研究药物停用和死亡的不良事件在各组之间没有显著差异。
异戈那肽口服溶液是安全的，但相对于安慰剂并没有降低发生溃疡性OM的风险。强化口腔卫生或在本试验中使用用于递送研究药物的赋形剂似乎降低了OM的风险和严重程度。我们的结果表明，抗菌干预可能不会对放射性OM的发病机制产生有意义的影响。
