Atorvastatin attenuates intestinal mucositis induced by 5-fluorouracil in mice by modulating the epithelial barrier and inflammatory response.

Chemotherapy-induced intestinal mucositis is a major side effect of cancer treatment. Statins are 3-hydroxy-3-methyl glutaryl coenzyme reductase inhibitors used to treat hypercholesterolemia and atherosclerotic diseases. Recent studies have demonstrated that atorvastatin (ATV) has antioxidant, anti-inflammatory, and resulting from the regulation of different molecular pathways. In the present study, we investigated the effects of ATV on intestinal homeostasis in 5-fluorouracil (5-FU)-induced mucositis. Our results showed that ATV protected the intestinal mucosa from epithelial damage caused by 5-FU mainly due to inflammatory infiltrate and intestinal permeability reduction, downregulation of inflammatory markers, such as Tlr4, MyD88, NF-κB, Tnf-a, Il1ß, and Il6 dose-dependent. ATV also improved epithelial barrier function by upregulating the mRNA transcript levels of mucin 2 (MUC2), and ZO-1 and occludin tight junction proteins. The results suggest that the ATV anti-inflammatory and protective effects on 5-FU-induced mice mucositis involve the inhibition of the TLR4/MYD88/NPRL3/NF-κB, iNos, and caspase 3.

Efficacy of Episil® in patients with hematologic malignancies: a comparative study.

BACKGROUND: Episil® is a nonabsorbable liquid medical material used to coat and protect the mucosa in patients with oral mucositis. A few studies have reported its efficacy in patients with head and neck cancer. However, reports on its use in patients with hematologic malignancies are scarce. Thus, we aimed to evaluate the efficacy of Episil for the treatment of oral mucositis in patients with acute myelogenous leukemia, malignant lymphoma, acute lymphocytic leukemia, multiple myeloma, and myelodysplastic syndrome. METHODS: Between May 2018 and March 2019, a total of thirty-seven patients with acute myelogenous leukemia, malignant lymphoma, acute lymphocytic leukemia, multiple myeloma, and myelodysplastic syndrome who received Episil® for the treatment of oral mucositis were included in this study. All patients were treated at the Hiroshima Red Cross and Atomic-bomb Surgery Hospital. To determine the severity of oral mucositis, 22 out of the 37 patients were interviewed and compared objectively using the Common Terminology Criteria for Adverse Events, version 3.0. In addition, subjective measures of the effects of oral mucositis were assessed using an original evaluation protocol (a unique evaluation chart specific to the Department of Oral Surgery, Hiroshima Red Cross & Atomic-bomb Survivors Hospital). RESULTS: Out of 37 participants recruited in the study, 31 (84%) described the sensation of Episil® as very good or good. Moreover, the severity of mucositis was found to decrease after the use of Episil® in seven patients out of 22 (19%), particularly in those with mucositis at multiple sites. Participants' evaluations revealed pain relief and improvement in speech and feeding functions. Participants with grade 3 mucositis reported a greater improvement in pain relief, speech, and feeding functions than those with grade 2 mucositis. CONCLUSIONS: This study suggests the efficacy of Episil® in treating oral mucositis in patients with hematologic malignancies, particularly in those with oral mucositis at multiple sites. In addition to pain relief, Episil® may improve speech and feeding functions.

BSP Implementation of Prevention and Treatment of Peri-implant Diseases - The EFP S3 Level Clinical Practice Guideline.

OBJECTIVES: to adapt the supranational European Federation of Periodontology (EFP) Prevention and Treatment of Peri-implant Diseases - The EFP S3 Level Clinical Practice Guideline for UK healthcare environment, taking into account a broad range of views from stakeholders and patients. SOURCES: This UK version, based on the supranational EFP guideline [1] published in the Journal of Clinical Periodontology, was developed using S3-level methodology, combining assessment of formal evidence from 13 systematic reviews with a moderated consensus process of a representative group of stakeholders, and accounts for health equality, environmental factors and clinical effectiveness. It encompasses 55 clinical recommendations for the Prevention and Treatment of Peri-implant Diseases, based on the classification for periodontal and peri-implant diseases and conditions [2]. METHODOLOGY: The UK version was developed from the source guideline using a formal process called the GRADE ADOLOPMENT framework. This framework allows for adoption (unmodified acceptance), adaptation (acceptance with modifications) and the de novo development of clinical recommendations. Using this framework, following the S3-process, the underlying evidence was updated and a representative guideline group of 111 delegates from 26 stakeholder organisations was assembled into four working groups. Following the formal S3-process, all clinical recommendations were formally assessed for their applicability to the UK and adoloped accordingly. RESULTS AND CONCLUSION: Using the ADOLOPMENT protocol, a UK version of the EFP S3-level clinical practice guideline for the Prevention and Treatment of Peri-implant Diseases was developed. This guideline delivers evidence- and consensus-based clinical recommendations of direct relevance to the UK healthcare community including the public. CLINICAL SIGNIFICANCE: The S3-level-guidelines combine evaluation of formal evidence, grading of recommendations and synthesis with clinical expertise of a broad range of stakeholders. The international S3-level-guideline was implemented for direct clinical applicability in the UK healthcare system, facilitating a consistent, interdisciplinary, evidence-based approach with public involvement for the prevention and treatment of peri-implant diseases.

An unmet need for pharmacology: Treatments for radiation-induced gastrointestinal mucositis.

Gastrointestinal mucositis (GIM) continues to be a significant issue in the management of abdominal cancer radiation treatments and chemotherapy, causing significant patient discomfort and therapy interruption or even cessation. This review will first focus on radiotherapy induced GIM, providing an understanding of its clinical landscape. Subsequently, the aetiology of GIM will be reviewed, highlighting diverse contributing factors. The cellular and tissue damage and associated molecular responses in GIM will be summarised in the context of the underlying complex biological processes. Finally, available drugs and pharmaceutical therapies will be evaluated, underscoring their insufficiency, and highlighting the need for further research and innovation. This review will emphasize the urgent need for improved pharmacologic therapeutics for GIM, which is a key research priority in oncology.

Peri-implant diseases and systemic inflammation: A preliminary analysis from a cross-sectional survey of patients with hypertension.

BACKGROUND: The aim of this study was to investigate the association between peri-implant diseases and systemic inflammation assessed by serum C-reactive protein (CRP) levels in a sample of patients with hypertension. METHODS: A total of 151 participants with hypertension were included in a cross-sectional study. The population was divided into six groups according to their peri-implant and periodontal status (healthy controls, mucositis, peri-implantitis, periodontitis, periodontitis and mucositis, periodontitis, and peri-implantitis). Linear, logistic regression, and correlation analyses were performed. RESULTS: CRP levels were statistically significantly higher in participants with periodontitis alone (median 3.2 mg/L, interquartile range [IQR] 1.8, p = 0.012), combined with mucositis (3.10 mg/L, IQR 2.35, p < 0.001) or peri-implantitis (2.7 mg/L, IQR 2.53, p = 0.002) when compared to the healthy controls (1 mg/L, IQR 1.2). This association was independent of age, sex, smoking status, and adiposity differences. Participants with periodontitis with and without peri-implant diseases had the greatest odds of exhibiting CRP > 3 mg/L (odds ratio = 7.3, 95% confidence interval 1.6-33.9). CONCLUSIONS: Peri-implant diseases are associated with systemic inflammation, but the nature of the association should be further investigated.

Efficacy of natural products in preventing oral mucositis resulting from cancer therapies: A network meta-analysis of randomized controlled trials.

BACKGROUND: Oral mucositis significantly compromises the quality of life for patients undergoing cancer therapies. This study aimed to evaluate the effectiveness of natural products in either preventing or alleviating oral mucositis resulting from cancer treatments. METHODS: A systematic review and network meta-analysis were conducted, sourcing data from the Cochrane Library, PubMed, Embase, Airiti Library, and Wan Fang Data Knowledge Service Platform until August 2023. The study was registered in PROSPERO (CRD42021285433). Confidence in Network Meta-Analysis (CINeMA) and R software 4.1.3 were used for analysis. RESULTS: From 1556 identified articles, 36 randomized controlled trials (RCTs) were analyzed, involving 2083 patients. Honey, notably, was found to significantly reduce the overall incidence of oral mucositis compared to standard care, with a relative risk (RR) of 0.80 (95% CI: 0.67-0.96). It was particularly effective against moderate-to-severe oral mucositis (grade ≥ 2), reducing incidence with RR of 0.48 (95% CI: 0.30-0.75) versus placebo and 0.56 (95% CI: 0.34-0.93) against standard care. Other natural products, including propolis, chamomile, and P. major L., also demonstrated significant efficacy in reducing the incidence of oral mucositis. Regarding pain relief, honey, and P. major L. emerged as effective, significantly reducing pain severity with a mean difference (MD) of -2.96 (95% CI: -3.80 to -1.94) compared to placebo. CONCUSSION: This network meta-analysis supports the use of honey, propolis, chamomile, and P. major L. as effective natural products in the prevention and treatment of oral mucositis among cancer patients. Specifically, honey is highlighted for its significant impact on reducing both the overall incidence and the severity of moderate-to-severe oral mucositis. By leveraging their anti-inflammatory and antioxidant properties, integrating these natural products into the standard care regimen could markedly improve the well-being of individuals undergoing cancer therapy.

Systemic Anti-Inflammatory Agents in the Prevention of Chemoradiation-Induced Mucositis: A Review of Randomised Controlled Trials.

Mucositis is a pathological condition characterised by inflammation and ulceration of the mucous membranes lining the alimentary canal, particularly in the mouth (oral mucositis) and the gastrointestinal tract. It is a common side effect of cancer treatments, including chemotherapy and radiotherapy, and it is sometimes responsible for treatment interruptions. Preventing mucositis throughout the alimentary tract is therefore crucial. However, current interventions mainly target either oral or gastrointestinal side effects. This review aimed to investigate the use of systemically administered anti-inflammatory agents to prevent mucositis in cancer patients undergoing cancer treatment. PubMed, Ovid, Scopus, Web of Science, WHO ICTRP and ClinicalTrials.gov were screened to identify eligible randomised controlled trials (RCTs). The published literature on anti-inflammatory agents provides mixed evidence regarding the degree of efficacy in preventing/reducing the severity of mucositis in most anticancer treatments; however, sample size continued to be a significant limitation, alongside others discussed. Our review yielded a list of several anti-inflammatory agents that exhibit potential mucositis-preventive effects in cancer patients undergoing cancer treatment, which can be used to inform clinical practice.

Dentist Involvement in the Treatment of Radiation-Induced Oral Mucositis-A Pilot Cross-Sectional Study.

Objectives: Oral mucositis (OM) occurs in more than 95% of patients irradiated in the head and neck area. This paper aims to determine the occurrence and characteristics of OM in patients with head and neck cancer (HNC), as well as the involvement of dentists/oral medicine specialists in treating such patients. Methods: This study was conducted at the Department of Otorhinolaryngology and Department of Oral Medicine, University Hospital Center Zagreb, from April to August 2022, on patients irradiated in the head and neck area. A unique OM questionnaire was created on the incidence, characteristics, oral care, and involvement of dentists in the overall care. Results: Thirty patients filled out the questionnaire. Of the 22 patients who had developed OM, 14 had grade-three OM. Ten patients were treated for OM in line with the instructions of an oral medicine specialist, eight based on the instructions of a specialist responsible for monitoring of the underlying disease, and four were not treated at all. Sixteen patients had not been referred to a dentist before the start of RT. Conclusions: These results showed insufficient care and treatment of OM, as well as insufficient involvement of dentists in the oncology team.

Survival outcomes and toxicity profiles among patients with nonmetastatic nasopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT) versus IMRT + carbon-ion radiotherapy: A propensity score-matched analysis.

OBJECTIVES: To compare survival outcomes and toxic effects among patients with newly diagnosed nonmetastatic nasopharyngeal carcinoma (NPC) when treated with intensity-modulated radiotherapy (IMRT) versus IMRT + carbon-ion radiotherapy (CIRT). METHODS: We performed a retrospective propensity score matching analysis (1:1) of patients treated with IMRT and IMRT + CIRT. Descriptive statistics were used to examine the baseline characteristics of the patients. Survival was estimated using the Kaplan-Meier method. Univariate and multivariable logistic regression analysis were used to identify the independent predictors of survival. We examined the association between risk factors and adverse events (AEs) using chi-square tests. Cox model and logistic regression were used to analyze AEs. RESULTS: Hundred and nine patients who received IMRT + CIRT were included and the median follow-up time was 20.6 months (range: 4.6-82 months). There were no statistically significant differences in locoregional failure-free survival, distant metastasis-free survival, disease-free survival, or overall survival between the two groups, but potentially better in IMRT + CIRT group (p > 0.05, respectively). Nodal boost was the only significant factor associated with LRFS and DFS on multivariable analysis. Thirty-seven patients (34.0%) developed grade 3 acute OMs and no grade 4 acute OMs were observed in IMRT + CIRT group. All patients in IMRT + CIRT group developed grade 1 dermatitis; while in the match group, 76 patients developed grade 1 dermatitis, 27 patients developed grade 2 dermatitis, 5 patients developed grade 3 dermatitis, 1 patient developed grade 4 dermatitis. IMRT + CIRT treatment was associated with a significant trend of lower grades of OM and dermatitis (p < 0.05, respectively). Any severe (i.e., grade 3) chronic AEs, such as xerostomia, skin fibrosis, temporal lobe necrosis, osteoradionecrosis, or radiation-induced optic neuropathy, was not observed. CONCLUSIONS: In this study, IMRT + CIRT was associated with significantly reduced acute toxicity burden compared with full course of IMRT, with excellent survival outcomes. Patients with persistent disease after treatment and treated with nodal boost had a worse outcome. More accurate assessments of IMRT + CIRT to primary nonmetastatic NPC patients will be imperative.

Eubacterium coprostanoligenes alleviates chemotherapy-induced intestinal mucositis by enhancing intestinal mucus barrier.

Chemotherapy-induced mucositis represents a severe adverse outcome of cancer treatment, significantly curtailing the efficacy of these treatments and, in some cases, resulting in fatal consequences. Despite identifying intestinal epithelial cell damage as a key factor in chemotherapy-induced mucositis, the paucity of effective treatments for such damage is evident. In our study, we discovered that Eubacterium coprostanoligenes promotes mucin secretion by goblet cells, thereby fortifying the integrity of the intestinal mucus barrier. This enhanced barrier function serves to resist microbial invasion and subsequently reduces the inflammatory response. Importantly, this effect remains unobtrusive to the anti-tumor efficacy of chemotherapy drugs. Mechanistically, E. copr up-regulates the expression of AUF1, leading to the stabilization of Muc2 mRNA and an increase in mucin synthesis in goblet cells. An especially significant finding is that E. copr activates the AhR pathway, thereby promoting the expression of AUF1. In summary, our results strongly indicate that E. copr enhances the intestinal mucus barrier, effectively alleviating chemotherapy-induced intestinal mucositis by activating the AhR/AUF1 pathway, consequently enhancing Muc2 mRNA stability.

Unveiling the Multifaceted Management of Oral Mucositis in Cancer Patients: A Narrative Review.

Oral mucositis (OM) is a major and common adverse reaction to cancer treatment, occurring in all patients who undergo radiation therapy or chemotherapy that includes the mucosal areas of the oral and oropharyngeal region. The pathophysiology of OM remains incompletely understood, and there are many unanswered questions about the risk factors for developing OM. Multidisciplinary clinicians and researchers must collaborate to better understand and expand treatment strategies for OM and other inflammatory conditions in oncology. This will lead to the development of more effective treatments and reduce the burden of OM in cancer patients. This article comprehensively reviews the risk factors and patient factors associated with OM, its pathogenesis, clinical presentation, grading, and management.

Efficacy of turmeric in the treatment of oral mucositis in patients with head and neck cancer after radiotherapy or chemoradiotherapy: a systematic review and meta-analysis.

Background: Oral mucositis is a major complication for head and neck cancer (HNC) patients after radiotherapy or chemotherapy. A meta-analysis was performed to assess the efficacy of turmeric in the treatment of oral mucositis in HNC patients. Methods: Randomized controlled trials investigating our topic were included in the meta-analysis. The clinical outcomes considered were the severity of oral mucositis, pain level, and weight loss. Results: A total of eight articles that met our inclusion criteria were included in our meta-analysis. At the 3-week follow-up visit, the turmeric group showed significantly lower grades of oral mucositis compared to the control group (p = 0.03). When compared to the placebo group, a significant difference in the degree of oral mucositis was observed at the 4-(p = 0.03) and 6-week (p < 0.00001) follow-up visits. No significant difference in pain levels was observed between the turmeric and control groups at any of the follow-up visits. However, a significant improvement in pain levels for the turmeric group when compared with the placebo group was observed only at the 6-week follow-up visit (p = 0.006). Interestingly, a significant improvement in pain levels was observed for the turmeric group at the 2-, 4-, 5-, and 6-week follow-up visits (p < 0.05) when compared to the non-placebo group. The turmeric group showed less weight loss than the control group at the final follow-up visit (p = 0.03). conclusion: Our meta-analysis showed that using turmeric may be effective in improving both the severity of oral mucositis and pain levels in HNC patients who have received radiotherapy or radiochemotherapy. In addition, the turmeric group experienced less weight loss.

Implementation of a light therapy team to administer photobiomodulation therapy: A standardized protocol to prevent and treat oral mucositis in the pediatric hematopoietic stem cell transplant population.

BACKGROUND: Oral mucositis (OM) is a painful and common complication of hematopoietic stem cell transplant (HSCT). The Children's Oncology Group recently published guidelines recommending photobiomodulation (PBM) for preventing and treating OM in pediatric HSCT patients. However, this is a rarely used intervention in pediatric hospitals. PROCEDURE: Patients undergoing allogeneic HSCT, or autologous HSCT for a neuroblastoma diagnosis, had PBM administered from the first day of conditioning to transplant Day +20. We successfully developed a standardized treatment protocol and workflow to ensure consistent and uniform delivery of PBM. In addition, clinical patient data were compared before and after PBM implementation. RESULTS: The administration of PBM at our center was feasible, but required dedicated staff. A registered nurse (RN) was determined to be the best fit to deliver PBM. Sixty-two patients received PBM from October 2022 to September 2023; patients from 2021 before PBM implementation were used for comparison. Patients receiving PBM were more likely (p = .03) to engage in teeth brushing (56/62 = 90%) compared to baseline (61/81 = 75%). Mean days of OM decreased from 11.3 to 9 days; patients who received PBM were less likely (p < .001) to be discharged on total parental nutrition (TPN) (11/62 = 18%) compared to baseline (50/82 = 61%). OM-related supportive care costs (TPN and patient-controlled anesthesia [PCA]) were lower (p = .02) for those who received PBM (median cost = $31,229.87 vs. $37,370.66). CONCLUSION: PBM, as the standard of care in the pediatric HSCT population, is safe, feasible, and well-tolerated. At our center, a dedicated RN was critical to providing standardized treatment and ensuring sustainability.

Efficacy of adjunctive photodynamic therapy to conventional mechanical debridement for peri-implant mucositis.

OBJECTIVE: This meta-analysis was conducted to assess the effectiveness of photodynamic therapy (PDT) as an adjunct to conventional mechanical debridement (CMD) for the management of peri-implant mucositis (p-iM). METHODS: We systematically searched four databases (PubMed, Embase, Web of Science, and Cochrane Library) for randomized controlled trials (RCTs) investigating PDT + CMD for p-iM from their inception to March 13, 2023. Meta-analysis was performed using RevMan 5.4 software. RESULTS: Seven RCTs met the inclusion criteria. The meta-analysis revealed that PDT + CMD treatment was more effective than CMD alone in reducing probing depth (PD) (Mean Difference [MD]: -1.09, 95% Confidence Interval [CI]: -1.99 to -0.2, P = 0.02) and plaque index (PI) (MD: -2.06, 95% CI: -2.81 to -1.31, P < 0.00001). However, there was no statistically significant difference in the improvement of bleeding on probing (BOP) between the PDT + CMD groups and CMD groups (MD: -0.97, 95% CI: -2.81 to 0.88, P = 0.31). CONCLUSIONS: Based on the current available evidence, this meta-analysis indicates that the addition of PDT to CMD significantly improves PD and PI compared to CMD alone in the treatment of p-iM. However, there is no significant difference in improving BOP.

Erythritol powder airflow for the treatment of peri-implant mucositis: A randomized controlled clinical trial.

OBJECTIVES: Peri-implant mucositis is a biofilm-related, reversible inflammatory disease that can evolve into peri-implantitis if not adequately treated. The aim of the present randomized controlled clinical trial was to evaluate the efficacy of air-abrasive powder as compared to chlorhexidine (CHX) for the treatment of peri-implant mucositis, in terms of clinical and patient-reported outcomes (PROMs) and occurrence of peri-implantitis 12 months after treatment. METHODS: In the control group, full-mouth calculus and plaque removal was performed with ultrasound and manual devices, and a 1.0% CHX gel was applied; in the test group, supra- and subgingival biofilm removal was performed using erythritol powder with a dedicated nozzle and calculus removal was performed with ultrasonic instruments if needed. Bleeding and plaque indexes, peri-implant probing depth and tissue level were measured at 1 week, and 1, 3, 6 and 12 months after treatment, while PROMs were evaluated up to 7 days after treatment. RESULTS: Among 80 included implants, 70 were analysed at 12 months follow-up (30 in the test group, 40 in the control group, and 20 subjects). Success rates (implant-level) in terms of bleeding index were significantly different between the test (96.7%) and control group (92.5%); as for PROMs, only taste sensation was significantly better in the test group. The test group was significantly correlated to the smallest changes in peri-implant probing depth between baseline and 3 months. CONCLUSIONS: The study showed that both treatment strategies are effective. This suggests that the use of air-abrasive powders could be used as an alternative biofilm removal method instead of adjunctive treatments with antiseptics.

Association of Insomnia and Obstructive Sleep Apnea with Worse Oral Mucositis and Quality of Life in Head and Neck Cancer Patients Undergoing Radiation Therapy.

BACKGROUND: Patients with head and neck cancer (HNC) undergoing radiation therapy (RT) often experience sleep disturbances that may contribute to oral mucositis (OM) and quality of life (QOL). METHODS: Patients with HNC treated with RT at a single institution were examined. Sleep questionnaires were given on the first day of RT to assess for insomnia and obstructive sleep apnea (OSA). Patient-reported QOL and oral mucositis were assessed during RT. Associations between insomnia and OSA with QOL were assessed using the Mann-Whitney U test. Linear mixed models assessed associations with OM. RESULTS: Among 87 patients, 34 patients (39%) had subthreshold or greater insomnia and 47 patients (54%) screened positive for OSA. Upon RT completion, patients with subthreshold or greater insomnia had worse physical function (p = 0.005), fatigue (p = 0.01), insomnia (p < 0.001), and sticky saliva (p = 0.002). Patients screening positive for OSA had worse physical function (p = 0.01), sticky saliva (p = 0.02), fatigue (p = 0.007), insomnia (p = 0.009), and pain (p = 0.005). Upon linear mixed model evaluation, subthreshold or greater insomnia (p = 0.01) and positive OSA screen (p = 0.002) were associated with worse OM. CONCLUSION: Insomnia and OSA are highly prevalent in patients with HNC undergoing RT. These sleep disturbances are associated with worse QOL and OM during treatment.

L-Glutamine Substantially Improves 5-Fluorouracil-Induced Intestinal Mucositis by Modulating Gut Microbiota and Maintaining the Integrity of the Gut Barrier in Mice.

SCOPE: This study investigates the potential of glutamine to mitigate intestinal mucositis and dysbiosis caused by the chemotherapeutic agent 5-fluorouracil (5-FU). METHODS AND RESULTS: Over twelve days, Institute of Cancer Research (ICR) mice are given low (0.5 mg kg-1) or high (2 mg kg-1) doses of L-Glutamine daily, with 5-FU (50 mg kg-1) administered between days six and nine. Mice receiving only 5-FU exhibited weight loss, diarrhea, abnormal cell growth, and colonic inflammation, correlated with decreased mucin proteins, increased endotoxins, reduced fecal short-chain fatty acids, and altered gut microbiota. Glutamine supplementation counteracted these effects by inhibiting the Toll-like receptor 4/nuclear factor kappa B (TLR4/NF-κB) pathway, modulating nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) oxidative stress proteins, and increasing mammalian target of rapamycin (mTOR) levels, thereby enhancing microbial diversity and protecting intestinal mucosa. CONCLUSIONS: These findings underscore glutamine's potential in preventing 5-FU-induced mucositis by modulating gut microbiota and inflammation pathways.

Comparisons of successful and failed Phase III trials of drugs and biologicals tested for mitigation of oral mucositis in patients being treated with radiotherapy with or without concomitant chemotherapy for cancers of the head and neck.

Oral mucositis (OM) remains a significant toxicity among patients being treated with radiotherapy (RT) alone or with concomitant chemotherapy (CRT) for cancers of the head and neck (HNC). Given its clinical significance as an unmet need and its potential commercial viability, the pharmaceutical industry has been actively pursuing an effective intervention. Despite this interest and activity, only a few agents have been studied in Phase III trials (n = 6). The objective of this study was to identify common features that differentiate successful and failed Phase III OM trials. We used the United States Patent and Trademark Office Patent Public Search database to search patents with "oral mucositis" in the claims. We then searched ClinicalTrials.gov and PubMed to determine if Phase III or Phase II trial data for identified biologics/drugs had been published. We assessed each Phase III and Phase II trial for characteristics that may be associated with trial success or failure. We considered a study as a "success" if the primary endpoint reached statistical significance, and we considered a study as "failure" if the primary endpoint did not reach statistical significance. Of the three successful Phase III trials, one investigated avasopasem manganese (Galera Therapeutics) and two examined palifermin (Amgen). The three failed trials included those evaluating dusquetide (Soligenix), iseganan hydrochloride (IntraBiotics Pharmaceuticals), and clonidine (Monopar Therapeutics). We found that differences in the level of sponsor funding, patient inclusion criteria including radiation source and concomitant chemotherapy regimen, and concordance of primary efficacy outcomes between Phase II and Phase III trials influenced outcomes. To properly design clinical trials for OM in HNC patients, it is important that researchers and sponsors take note of specific study characteristics associated with success or failure, particularly with Phase III trials where the risks and costs are the highest.