The COMPARE head-to-head, randomized controlled trial of SEL-212 (pegadricase plus rapamycin-containing nanoparticle, ImmTOR™) versus pegloticase for refractory gout.

OBJECTIVES: Serum urate (SU) lowering with PEGylated uricases in gout can reduce flares and tophi. However, treatment-emergent anti-drug antibodies adversely affect safety and efficacy and the currently approved PEGylated uricase pegloticase requires twice-monthly infusions. Investigational SEL-212 therapy aims to promote uricase-specific tolerance via monthly sequential infusions of a proprietary rapamycin-containing nanoparticle (ImmTOR) and pegadricase. METHODS: COMPARE was a randomized, phase 2, open-label trial of SEL-212 vs pegloticase in adults with refractory gout. SEL-212 [ImmTOR (0.15 mg/kg) and pegadricase (0.2 mg/kg)] was infused monthly or pegloticase (8 mg) twice monthly for 6 months. The primary endpoint was the proportion of participants with SU <6 mg/dl for ≥80% of the time during 3 and 6 months. Secondary outcomes were mean SU, gout flares, number of tender and/or swollen joints and safety. RESULTS: During months 3 and 6 combined, numerically more participants achieved and maintained a SU <6 mg/dl for ≥80% of the time with SEL-212 vs pegloticase (53.0% vs 46.0%, P = 0.181). The percentage reductions in SU levels were statistically greater during months 3 and 6 with SEL-212 vs pegloticase (-73.79% and -47.96%, P = 0.0161). Reductions in gout flare incidence and number of tender and/or swollen joints were comparable between treatments. There were numerical differences between the most common treatment-related adverse events of interest with SEL-212 and pegloticase: gout flares (60.2% vs 50.6%), infections (25.3% vs 18.4%) and infusion-related reactions (15.7% vs 11.5%), respectively. Stomatitis (and related terms) was experienced by eight participants (9.6%) with SEL-212 and none with pegloticase. Stomatitis, a known event for rapamycin, was associated with ImmTOR only. CONCLUSIONS: SEL-212 efficacy and tolerability were comparable to pegloticase in refractory gout. This was associated with a substantial reduction in treatment burden with SEL-212 due to decreased infusion frequency vs pegloticase. CLINICAL TRIAL REGISTRATION: NCT03905512.

Disproportionality Analysis of Stomatitis Associated with Anticancer Drugs Using the Japanese Adverse Drug Event Report Database.

INTRODUCTION: Anticancer drug-induced stomatitis can affect a patient's quality of life and the continuation of drug treatment. Although there have been reports of the occurrence of stomatitis associated with anticancer agents in clinical trials, few Japanese participants have been enrolled in clinical trials and have not been sufficiently investigated. In addition, there has been little attention on research on anticancer drugs associated with stomatitis by patient stratification with different carcinogenic sites. Therefore, the aim of this study was to determine the disproportionality associated with stomatitis for various types of anticancer drugs in different types of cancer patients using the Japanese Adverse Drug Event Report (JADER) database. METHODS: The aim of this study was to identify the disproportionality of stomatitis by analyzing the type of anticancer drug and cancer patients using the Japanese Pharmacovigilance Database. Data obtained from spontaneous reports of adverse events with more than 10 stomatitis outbreaks reported in the JADER database between April 2004 and March 2023 were analyzed. The safety signal for an adverse event was defined as the lower limit of the 95% confidence interval of the reported odds ratio of >1. RESULTS: There were 6,178 reports of drugs associated with stomatitis. Among these, 41 drugs were suggested to be associated with stomatitis, and 41 drugs were detected as signals. These drugs were classified based on their efficacy: antipyrimidines (six drugs), folate metabolism antagonists (three drugs), alkylating agents (four drugs), platinum (three drugs), topoisomerase inhibitors (three drugs), microtubule inhibitors (three drugs), mammalian target of rapamycin (mTOR) inhibitors (two drugs), kinase inhibitors (seven drugs), anti-growth factor antibodies (five drugs) immune checkpoint inhibitors (one drug), and others (four drugs). CONCLUSION: The drugs that may be associated with stomatitis were cell cycle-dependent drugs, epidermal growth factor receptor-tyrosine kinase inhibitors, and mTOR inhibitors. Moreover, this study suggested that anti-growth factor antibodies and immune checkpoint inhibitors may be associated with stomatitis development.

Contact allergies to dental materials in patients.

BACKGROUND: Concerns regarding contact allergies and intolerance reactions to dental materials are widespread among patients. Development of novel dental materials and less frequent amalgam use may alter sensitization profiles in patients with possible contact allergy. OBJECTIVES: To analyse current sensitization patterns to dental materials in patients with suspected contact allergy. METHODS: This retrospective, multicentre analysis from the Information Network of Departments of Dermatology (IVDK) selected participants from 169 834 people tested in 2005-2019 and registered with (i) an affected area of 'mouth' (and 'lips'/'perioral'), (ii) with the dental material in question belonging to one of three groups (dental filling materials, oral implants or dentures or equivalents) and (iii) with patch-testing done in parallel with the German baseline series, (dental) metal series and dental technician series. RESULTS: A total of 2730 of 169 834 tested patients met the inclusion criteria. The patients were predominantly women (81.2%) aged ≥ 40 years (92.8%). The sensitization rates with confirmed allergic contact stomatitis in women (n = 444) were highest for metals (nickel 28.6%, palladium 21.4%, amalgam 10.9%), (meth)acrylates [2-hydroxyethyl methacrylate (HEMA) 4.8%] and the substances propolis (6.8%) and 'balsam of Peru' (11.4%). The most relevant acrylates were HEMA, 2-hydroxypropyl methacrylate, methyl methacrylate, ethylene glycol dimethacrylate and pentaerythritol triacrylate. Few men were diagnosed with allergic contact stomatitis (n = 68); sensitization rates in men were highest for propolis (14.9%) and amalgam (13.6%). CONCLUSIONS: Allergic contact stomatitis to dental materials is rare. Patch testing should not only focus on metals such as nickel, palladium, amalgam and gold, but also (meth)acrylates and the natural substances propolis and 'balsam of Peru'.

Single nucleotide polymorphisms conferring susceptibility to leukemia and oral mucositis: a multi-center pilot study of patients prior to conditioning therapy for hematopoietic cell transplant.

PURPOSE: Leukemias have been associated with oral manifestations, reflecting susceptibility to cancer therapy-induced oral mucositis. We sought to identify SNPs associated with both leukemia and oral mucositis (OM). METHODS: Whole exome sequencing was performed on leukemia and non-cancer blood disorder (ncBD) patients' saliva samples (N = 50) prior to conditioning therapy. WHO OM grading scores were determined: moderate to severe (OM2-4) vs. none to mild (OM0-1). Reads were processed using Trim Galorev0.6.7, Bowtie2v2.4.1, Samtoolsv1.10, Genome Analysis Toolkit (GATK)v4.2.6.1, and DeepVariantv1.4.0. We utilized the following pipelines: P1 analysis with PLINK2v3.7, SNP2GENEv1.4.1 and MAGMAv1.07b, and P2 [leukemia (N = 42) vs. ncBDs (N = 8)] and P3 [leukemia + OM2-4 (N = 18) vs. leukemia + OM0-1 (N = 24)] with Z-tests of genotypes and protein-protein interaction determination. GeneCardsSuitev5.14 was used to identify phenotypes (P1 and P2, leukemia; P3, oral mucositis) and average disease-causing likelihood and DGIdb for drug interactions. P1 and P2 genes were analyzed with CytoScape plugin BiNGOv3.0.3 to retrieve overrepresented Gene Ontology (GO) terms and Ensembl's VEP for SNP outcomes. RESULTS: In P1, 457 candidate SNPs (28 genes) were identified and 21,604 SNPs (1016 genes) by MAGMAv1.07b. Eighteen genes were associated with "leukemia" per VarElectv5.14 analysis and predicted to be deleterious. In P2 and P3, 353 and 174 SNPs were significant, respectively. STRINGv12.0 returned 77 and 32 genes (C.L. = 0.7) for P2 and P3, respectively. VarElectv5.14 determined 60 genes from P2 associated with "leukemia" and 11 with "oral mucositis" from P3. Overrepresented GO terms included "cellular process," "signaling," "hemopoiesis," and "regulation of immune response." CONCLUSIONS: We identified candidate SNPs possibly conferring susceptibility to develop leukemia and oral mucositis.

Evaluation of oral mucositis level and affecting factors in cancer patients receiving chemotherapy.

OBJECTIVES: This study aimed to evaluate the severity of oral mucositis and the contributing factors among cancer patients undergoing chemotherapy. METHODS: This study was planned cross-sectional. The study was conducted at a medical oncology clinic between January and July 2022. The sample consisted of 245 patients with cancer receiving chemotherapy. Data were collected using a personal, oral health and disease-related characteristics questionnaire and the World Health Organization Oral Mucositis Assessment Scale by researchers. Intraoral examination of the patients was carried out by researchers. The data were analyzed by independent-sample t-tests, Chi-square tests, paired-sample t-tests, and multivariate logistic regression (p < 0,05). RESULTS: The patients had mean age 62.31 ± 10.70. Patients of 32.7% were with lung cancer. 52%of the patients (n = 128) receiving chemotherapy developed oral mucositis. The independent variables the presence chronic disease(OR:1.85), chemotherapy protocol (OR:3.52) and the dependent variables ECOG performance score (OR:2.25) were variable that affected the development of oral mucositis (p < 0.05). Patients of 35.5% were oral mucositis score of 1. Patients those who had breast cancer, who received doxorubicin or cyclophosphamide chemotherapy protocols, and who had previously developed oral mucositis were found to have a higher rate of oral mucositis (p < 0.05). In addition, oral mucositis was more prevalent in patients with chronic diseases other than cancer (57%), those who used medication continuously (57.2%), those with oral and dental diseases (56.9%), those who had dental check-ups before cancer treatment (79.2%), and those who had information about oral mucositis(70.2%) (p < 0.05). CONCLUSION: In conclusion, nearly half of the patients (52%, n = 128) receiving chemotherapy developed oral mucositis and of all patients of 35.5% had an oral mucositis score of 1 in the second round of chemotherapy. Patients those who had breast cancer, who received doxorubicin or cyclophosphamide chemotherapy protocols, and who had previously developed oral mucositis were found to have a higher rate of oral mucositis.

Association between salivary inflammatory mediators and oral mucositis in patients with cancer undergoing chemotherapy.

PURPOSE: Oral mucositis is a severe adverse event in patients undergoing chemotherapy and radiotherapy that may lead to the termination of cancer treatment. This study aimed to elucidate the relationship between salivary inflammatory mediators and oral mucositis in patients undergoing chemotherapy. METHODS: This prospective cohort study included 167 patients who underwent chemotherapy at our institution between June 2020 and November 2023. We evaluated the association between chemotherapy-induced oral mucositis and salivary inflammatory mediators using multiple comparison tests and logistic regression analyses. RESULTS: Of the 167 patients, 67 (40.1%) had oral mucositis. Dunn's multiple comparison test revealed that interleukin-6 was significantly higher in oral mucositis of grades 2 and ≥ 3 (P < 0.01) and tumor necrosis factor (TNF)-α was significantly higher in oral mucositis of grades 3-4 (P < 0.01). Logistic regression analysis showed that the risk of oral mucositis was significantly higher for tumor necrosis factor (TNF)-α > 4.4 pg/mL than for TNF-α ≤ 4.4 pg/mL (adjusted odds ratio, 2.4; 95% confidence interval, 1.1-5.3; P = 0.03). CONCLUSION: Saliva is useful in evaluating inflammation in patients with chemotherapy-induced oral mucositis. Furthermore, TNF-α may be a predictive marker for the severity of oral mucositis in patients undergoing chemotherapy.

Association of oral mucositis induced by anthracycline-cyclophosphamide and subsequent docetaxel treatment for perioperative breast cancer.

PURPOSE: Anthracycline-cyclophosphamide followed by docetaxel-containing chemotherapy is effective for perioperative breast cancer treatment. However, these treatments frequently induce oral mucositis (OM), with an incidence ranging from 20 to 50%. The association of OM development between different chemotherapeutic treatments remains unclear. Consequently, this study aimed to compare OM development during docetaxel-containing chemotherapy between patients with and without OM experience during previous anthracycline-cyclophosphamide treatments to assess the association between OM development and treatment regimens. METHODS: Seventy-two patients with breast cancer receiving anthracycline-cyclophosphamide followed by docetaxel-containing chemotherapy as a perioperative treatment were categorized into the control (no prior OM experience with anthracycline-cyclophosphamide) and OM-experience (OM development during previous treatment) groups and retrospectively evaluated. The primary endpoint was the incidence of all-grade OM in the first docetaxel-containing chemotherapy cycle. Additionally, the incidences of OM and dysgeusia during all treatment cycles and factors associated with the incidence of OM were evaluated. RESULTS: The incidence of all-grade OM in the first cycle was significantly higher in the OM-experience group (54.2%) than in the control group (10.4%; P < 0.0001). Furthermore, its incidence in all treatment cycles was higher in the OM-experience group (66.7%) than in the control group (12.5%, P < 0.0001). However, the incidence of dysgeusia did not differ between the groups. Multivariate logistic regression analysis revealed OM experience during previous anthracycline-cyclophosphamide treatment and concomitant pertuzumab use as independent risk factors for OM development in subsequent docetaxel-containing chemotherapy. CONCLUSION: Our study suggests that patients experiencing OM with anthracycline-cyclophosphamide during perioperative breast cancer treatment exhibit symptoms following subsequent docetaxel-containing chemotherapy.

The Efficacy of Three Different Oral Hygiene Regimens in Preventing Chemotherapy-Induced Oral Mucositis in Pediatric Patients Receiving Hematopoietic Stem Cell Transplantation.

BACKGROUND: Oral mucositis is one of the side effects developed post-hematopoietic stem cell transplant. This retrospective study aimed to assess the efficacy of a mouthwash mixture (lidocaine, sodium alginate, sucralfate, pheniramine) versus hyaluronic acid and a solution of sodium bicarbonate in terms of healing time and weight gain in the treatment of oral mucositis in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation with hemato-oncological malignancies. METHODS: A total of 171 patients that received chemotherapy for the hematopoietic stem cell transplant were divided into three groups; group 1, treated with a mixed mouthwash of lidocaine, sodium alginate, sucralfate, and pheniramine; group 2, treated with hyaluronic acid; and group 3, treated with an aqueous solution of 5% sodium bicarbonate. Weight and mucositis scale scores derived from medical records of patients. RESULTS: There was a statistically significant difference in the mucositis scale scores between the groups on the transplant day and days 5, 10, 15 and 20 after the transplantation. At these measurement points, Group 2 (receiving hyaluronic acid) had a lower score, and Group 3 (who received sodium bicarbonate) had a higher score, especially on days 5 and 10 after the transplantation. CONCLUSION: The results suggest that hyaluronic acid is a more effective treatment option than the other oral care solutions that are frequently used for prophylaxis and treatment of oral mucositis.

Risk factors for oral mucositis in patients with solid tumors under treatment with cetuximab: a retrospective cross-sectional study.

BACKGROUND: This study retrospectively analyzed the risk factors for oral mucositis (OM) during cetuximab treatment. MATERIAL AND METHODS: We screened patients using cetuximab and retrospectively evaluated the presence of OM based on medical records. We collected information from 2 years of evaluations. Patient medical records were reviewed to obtain data on chemotherapy cycle and dose, sex, age, primary tumor, TNM stage, and head and neck radiotherapy (HNR) history. The X2 test and multinomial logistic regression were used for statistical analysis (SPSS 20.0, p < 0.05). RESULTS: Among 1831 patients, OM was showed in 750 in any grade (41%), during cetuximab treatment. Most patients were female (n=944, 51.6%), <70years-old (n=1149, 62.8%), had larynx cancer (n=789, 43.1%) in T4 (n=579, 47.7%), N0 (n=509, 52.6%) stages. Primary tumor surgery was performed in 1476 (80.6%) patients, radiotherapy in 606 (33.1%) patients and cetuximab protocols most used involved up to four cycles (n=1072, 58.5%) of <400mg (n=996, 54.4%) cetuximab doses. Female (OR [odds ratio] = 2.17, CI95% = 1.26-3.75), >70 years-old patients (OR = 16.02, CI95% = 11.99-21.41), with HHNR (OR = 1.84, 1.41-2.40), treated with >4 cycles (OR = 1.52, CI95% = 1.16-2.01) and high doses of cetuximab (OR = 3.80, CI95% = 2.52-5.71) are the greatest risk factors for OM. CONCLUSIONS: Since the clinical benefit of cetuximab in the treatment of older patients is limited and there is a high OM, especially in women with head and neck treated with radiotherapy, high doses and a high number of cetuximab cycles must be administered with caution.

Therapeutic effectiveness of anlotinib combined with etoposide in extensive-stage small-cell lung cancer: a single-arm, phase II trial.

BACKGROUND: Anlotinib plus chemotherapy as first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC) achieves good efficacy, but there is still room for improvement. This clinical study examined the effectiveness of anlotinib plus etoposide for maintenance therapy in ES-SCLC. METHODS: The current single-arm, prospective phase II study was performed at Jiangsu Cancer Hospital (March 2019 to March 2022). After successful primary etoposide-based therapy, anlotinib was administered at 12 mg/day on days 1 to 14 of 21-day cycles until disease progression or consent withdrawal. All patients also received etoposide at 50 mg/day on days 1 to 14 of 21-day cycles for a maximum of six cycles. Progression-free survival (PFS) constituted the primary study endpoint. Secondary endpoints were overall survival (OS), objective remission rate (ORR), disease control rate (DCR), and safety. In addition, adverse events (AEs) were assessed. RESULTS: Twenty-eight patients were treated. Median PFS and OS were 8.02 (95%CI 5.36-10.67) and 11.04 (95%CI 10.37-11.68) months, respectively. Totally 9 and 18 participants showed a partial response and stable disease, respectively; ORR and DCR were 32.14% and 96.43%, respectively. The commonest all-grade AEs were fatigue (n = 11, 39.28%), hypertension (n = 11, 39.28%), loss of appetite (n = 9, 32.14%), oral mucositis (n = 7, 25.00%) and proteinuria (n = 6, 21.40%). Grade 3-4 AEs included fatigue (n = 4, 14.28%), hypertension (n = 2, 7.14%), hand and foot syndrome (n = 2, 7.14%), oral mucositis (n = 1, 3.57%), hemoptysis (n = 1, 3.57%), proteinuria (n = 1, 3.57%), gingival bleeding (n = 1, 3.57%), and serum creatinine elevation (n = 1, 3.57%). CONCLUSION: Maintenance anlotinib plus etoposide achieves promising PFS and OS in clinical ES-SCLC. REGISTRATION NUMBER: ChiCTR1800019421.

Chemotherapy-Induced Oral Complications and Prophylaxis Strategies.

Cancer is currently a significant therapeutic challenge and is frequently connected with numerous adverse effects. Despite many improvements in chemotherapy, oral complications are common, leading to poor quality of life and chemotherapeutic dose reduction, which impair survival. This review summarizes the most common dental complications in patients receiving chemotherapy. We mainly focus on oral mucositis as it is a major cause of dose-limiting toxicity. Furthermore, oral candidiasis, viral infections, and xerostomia will be discussed. Conclusions: preventing complications is significantly more important than treating them. All patients beginning systemic anticancer treatment should undergo a thorough oral examination and get appropriate prophylaxis.

Efficacy of curcumin for amelioration of radiotherapy-induced oral mucositis: a preliminary randomized controlled clinical trial.

BACKGROUND: Oral mucositis (OM) is one of the main problems in almost all patients undergoing head and neck radiotherapy (RT). Owning to the antioxidant and anti-inflammatory properties of curcumin, the effect of both oral and topical formulations of curcumin was assessed on radiation-induced OM (ROM) in this study. METHODS: The safety and efficacy of curcumin mouthwash 0.1% (w/v) and curcumin-nanocapsule were evaluated in ameliorating severity and pain/burning associated with OM during RT. The current randomized, placebo-controlled trial was conducted on 37 patients with head and neck cancers. Patients with grades 1 to 3 of ROM were randomized to receive one of the three interventions: curcumin mouthwash (0.1% w/v); Sinacurcumin soft gel containing 40 mg curcuminoids as nano-micelles (SinaCurcumin®40); or placebo mouthwash with a similar transparent appearance to curcumin mouthwash for 1 min three times daily during RT. Study evaluations were conducted at baseline and weekly thereafter for up to 3 weeks using the Numeric rating scale (NRS) and world health organization (WHO) scale. RESULTS: Among the 45 patients randomized, 37 (mean (SD) age of 53.36 (15.99) years; 14 [37.8%] women) completed the treatment according to the protocol. Patients treated with either oral or topical curcumin showed a significantly reduced severity and burning related to OM during the first 3 weeks after administration (P-Value < 0.001) as compared with the placebo. At study termination, more than 33% of subjects utilizing curcumin mouthwash and 15% of patients utilizing curcumin-nanocapsule remained ulcer free while all of the placebo-receiving subjects had OM. The reduction of NRS and WHO scale between curcumin groups was comparable without significant differences. CONCLUSION: Both curcumin mouthwash and nanocapsule were effective, safe, and well-tolerated in the treatment of radiation-induced OM. Higher doses of curcumin and larger sample sizes can be used for further investigation in future studies. TRIAL REGISTRATION: https://irct.ir/ IRCT20190810044500N17 (13/08/2021).

Hangeshashinto for prevention of oral mucositis in patients undergoing hematopoietic stem cell transplantation: a randomized phase II study.

PURPOSE: Oral mucositis (OM) is a side effect associated with cancer treatment. Hangeshashinto (HST), a Kampo medicine, was originally prescribed to treat diarrhea, gastritis, and stomatitis. Several reports have described the effects of HST for OM induced by chemotherapy in patients with gastric or colorectal cancer. In this study, the effects of HST for prevention of OM were investigated in patients undergoing hematopoietic stem cell transplantation (HSCT). METHODS: Thirty patients scheduled to receive allogeneic grafts were enrolled from July 2020 to December 2021. They were randomly assigned to two groups and instructed to wash their mouth using HST dissolved in saline solution or using only saline solution three times a day. The observation period was from the initiation date of the conditioning regimen to the date of engraftment, and the end point was the incidence of OM. RESULTS: Eighteen patients developed OM, the most severe of which was Grade (G)3. There was no significant difference in the incidence of OM between the HST group and the control group. However, a negative correlation tended to be observed between the duration using HST use and the duration of OM (G2-3: P = 0.027, G3: P = 0.047). CONCLUSIONS: The present study demonstrated that HST use did not clearly inhibit onset of OM but showed a tendency to inhibit OM exacerbation. However, further studies are necessary to fully understand the effects of HST on OM in patients undergoing HSCT. TRIAL REGISTRATION: This study was registered in the Japan Registry of Clinical Trials on 7 May 2020 (jRCTs071200012).

Protective effect of cryotherapy against oral mucositis among allogeneic hematopoietic stem cell transplant recipients using melphalan-based conditioning.

PURPOSE: Oral cryotherapy is an effective method to prevent oral mucositis (OM) induced by chemotherapeutic agents, such as melphalan (Mel). However, there is limited data about cryotherapy in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients; thus, the current study aimed to examine the efficacy of cryotherapy among allo-HSCT recipients treated with Mel-containing regimens. METHODS: Medical records of 78 consecutive allo-HSCT recipients were retrospectively analyzed. Baseline characteristics and clinical courses between the patients who received cryotherapy (cryotherapy group, n = 42) and those who did not (control group, n = 36) were compared, especially focusing on methotrexate (MTX) use as a part of graft-versus-host disease (GVHD) prophylaxis. RESULTS: Binary logistic regression analysis revealed that a higher dose of Mel (OR, 3.82; 95%CI, 1.085-13.46; P = 0.037) or MTX use (OR, 7.61; 95% CI, 2.41-23.97; P < 0.001) was associated with the incidence of OM. MTX use was also significantly associated with the duration of OM (ß = 0.515; 95% CI, 9.712-21.636; P < 0.001). Among 31 patients without MTX use, cryotherapy was associated with a significant reduction of OM development (0% in the cryotherapy group vs 35% in the control group, P = 0.021). We did not find such an association in 47 patients with MTX use. CONCLUSION: Cryotherapy was useful to prevent the incidence of OM in allo-HSCT recipients in the cases without MTX for GVHD prophylaxis.

Efficacy of bioadhesives in the management of oral mucositis in patients undergoing radio-chemotherapy for treatment of head and neck cancer-a systematic review and meta-analysis.

BACKGROUND: Management of head and neck cancers requires a multidisciplinary approach where surgery followed by radio and chemotherapy is the mainstay of treatment. The above-mentioned treatment can cause mucositis, a severely debilitating side effect. This can have a significant impact on quality of life. A recent advancing mode of drug delivery is the bioadhesive system. This interacts with mucosa by adhering to it and thereby improving the efficacy of the therapeutic agent delivered. AIM AND OBJECTIVE: The purpose of this systematic review is to evaluate the effectiveness of bioadhesives in reducing oral mucositis and relieving pain associated with mucositis in head and neck cancer patients receiving radio-chemotherapy. MATERIALS AND METHOD: Studies assessing the effectiveness of bioadhesives for the treatment of radiation-induced oral mucositis were retrieved from specialized databases (PubMed/MEDLINE, Scopus, ProQuest, Google Scholar, LILACS, OpenGrey) as well as institutional repositories. Data on incidence, pain reduction, resolution, and improvement of oral mucositis using bioadhesive were compiled. A Cochrane tool was used for randomized controlled trials and a JBI tool for non-randomized controlled trials and observational studies to assess the quality of included studies. Based on the eligible study data, a meta-analysis was conducted with STATA version 16, 2019 software, and 95% confidence intervals and p values greater than 0.05. RESULTS: A total of 15 studies were included which assessed the effectiveness of bioadhesives in managing mucositis and its associated pain. Studies included in the review described either reduction, resolution, or incidence of oral mucositis respectively. A total of three meta-analyses were conducted to assess the incidence of oral mucositis and the pain associated with it, as well as the reduction in incidence. Bioadhesives showed statistically significant differences in the incidence of severe mucositis (p = 0.04). A meta-analysis comparing bioadhesives efficacy in reducing mucositis and pain associated with it found no statistically significant differences (p = 0.36). CONCLUSION: Bioadhesives are emerging as a novel drug delivery method for treating radio-chemotherapy-induced oral mucositis because of their rapid absorption and easy application. Regardless of its benefits, clinical trials comparing it with conventional treatment methods are necessary to assess its efficacy in treating oral mucositis.

Identification of potential molecular mechanisms and candidate drugs for radiotherapy- and chemotherapy-induced mucositis.

BACKGROUND: Radiotherapy-induced oral mucositis (RIOM) and chemotherapy-induced oral mucositis (CIOM) are common complications in cancer patients, leading to negative clinical manifestations, reduced quality of life, and unsatisfactory treatment outcomes. OBJECTIVE: The present study aimed to identify potential molecular mechanisms and candidate drugs by data mining. METHODS: We obtained a preliminary list of genes associated with RIOM and CIOM. In-depth information on these genes was explored by functional and enrichment analyses. Then, the drug-gene interaction database was used to determine the interaction of the final enriched gene list with known drugs and analyze the drug candidates. RESULTS AND CONCLUSION: This study identified 21 hub genes that may play an important role in RIOM and CIOM, respectively. Through our data mining, bioinformatics survey, and candidate drug selection, TNF, IL-6, and TLR9 could play an important role in disease progression and treatment. In addition, eight candidate drugs (olokizumab, chloroquine, hydroxychloroquine, adalimumab, etanercept, golimumab, infliximab, and thalidomide) were selected by the drug-gene interaction literature search additionally, as candidates for treating RIOM and CIOM.

The effects of Ankaferd hemostat on preventing oral mucositis in colorectal cancer patients receiving chemotherapy.

INTRODUCTION: New agents are introduced each day to be used in the prevention and treatment of mucositis in cancer treatment. One of those agents is the Ankaferd hemostat. Ankaferd hemostat has pleiotropic effects and anti-infective characteristics in tissue healing. METHODS: The study was designed as a randomized controlled experimental study. The sample of the study comprised a total of 66 patients (33 patients in the Ankaferd hemostat group and 33 patients in the sodium bicarbonate group) with colorectal cancer who received FOLFOX combination chemotherapy treatment in the first cycle of chemotherapy to prevent mucositis. Participants who met the criteria were randomly assigned to the groups. Before the patient received chemotherapy, ECOG performance score and Oral Mucositis Grading Scale were applied on the 7th day and 15th day. The Ankaferd hemostat group brushed teeth at least twice a day for 2 min and gargled with Ankaferd hemostat twice for 2 min for 2 weeks. The sodium bicarbonate group brushed teeth at least 2 min a day and gargled with sodium bicarbonate 4 times for 2 min for 2 weeks. The Consolidated Standards of Reporting Trials diagram was used to illustrate the randomization of patients. RESULTS: When the Ankaferd hemostat group is compared with the sodium bicarbonate group, there is a significant difference in favor of the Ankaferd hemostat group in the mucositis grade on the 7th day and 15th day after chemotherapy (p < 0.05). In the binary logistic regression analysis, among the factors affecting the formation of mucositis on the 7th day, only neutrophil and thyroid-stimulating hormone (TSH) were included in the model, while only the TSH variable is statistically significant. CONCLUSIONS: It was determined that Ankaferd hemostat is effective in preventing oral mucositis due to chemotherapy in adult patients diagnosed with colorectal cancer. In addition, it has been suggested to conduct new studies on the effectiveness of Ankaferd hemostat in the prevention of mucositis in different groups. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (ID: NCT05438771, Date: 25.06.2022).

Oral hygiene protocols reduce the severity and incidence of oral mucositis during antineoplastic treatment: a systematic review and meta-analysis of randomized and non-randomized clinical trials.

OBJECTIVE: The objective of this systematic review was to determine whether oral and dental hygiene protocols (DHPs) reduce the incidence and severity of oral mucositis (OM) during antineoplastic treatment. MATERIALS AND METHODS: This PROSPERO-registered systematic review (CRD42021295322) was based on searches of publicly accessible databases, including PubMed, Scopus, Web of Science, LILACS, EBSCOhost, LIVIVO, Embase, and gray literature (Google Scholar, ProQuest, and Energy) until December 2021. Twenty-five articles from these searches and 14 articles retrieved from the references therein were evaluated in this systematic review and meta-analysis. The risk of bias (RoB) was assessed using RoB-2 and ROBINS-I for randomized (RCT) and non-randomized (n-RCT) clinical trials, respectively. A meta-analysis was performed on RCTs and n-RCTs in two subgroups to evaluate oral mouth rinses or DHP. GRADE-pro was used to assess the degree of certainty of the evidence. RESULTS: Of the 3367 articles retrieved, 25 RCTs and 14 n-RCTs involving 2109 and 754 patients, respectively, were included in the analyses. RoB was low for RCTs and moderate-to-very severe for n-RCTs. High heterogeneity and publication RoB were identified. In RCTs, mouth rinses (p = 0.830) and DHP (p = 0.100) did not reduce the incidence of OM. However, mouth rinses strongly reduced the severity of OM (p < 0.001; Cohen's d = - 1.87, 95% confidence interval [CI] = - 2.49 to - 1.24). In non-RCTs, mouth rinses (p < 0.001) and DHP (p < 0.001) reduced the relative risk of OM 0.38 (95% CI = 0.24 to 0.59) and 0.64 (95% CI = 0.53 to 0.70) times, respectively. In addition, DHP strongly reduced OM severity (Cohen's d = - 0.81, 95% CI = - 1.03 to - 0.59). GRADE-pro showed high certainty of OM severity and incidence in RCTs and non-RCTs, respectively, and low (OM incidence in RCTs) to very low (OM severity in non-RCTs) certainty in other outcomes. CONCLUSION: DHPs strongly reduce the severity and moderately reduce the incidence of OM. However, further studies with low heterogeneity are needed to validate these findings.

Assessment of thyme honey oral gel for the prevention of adriamycin and cyclophosphamide chemotherapy-induced oral mucositis in patients with breast cancer.

PURPOSE: Oral mucositis (OM) is a common complication of cancer treatment that has an impact on a patient's quality of life and the outcome of cancer therapy. This trial evaluated the effect of thyme honey oral gel for the prevention of chemotherapy-induced OM. METHODS: One hundred ten breast cancer patients who received their first cycle of chemotherapy with adriamycin (60 mg/m2) and cyclophosphamide (600 mg/m2) were randomly recruited into two groups: group A were patients who followed general oral hygiene recommendations and rinsing saline 3 times a day, and group B were patients with similar protocol but supplied with our formulated oral gel to be applied 2 to 4 times a day. Patients were assessed by the World Health Organization (WHO) oral mucositis grading scales and self-assessment daily questionnaire. RESULTS: The use of thyme honey was associated with diminishing incidence of OM grade ≥ 2 (95% CI, 0.12 to 0.90; P = 0.030), duration of OM (- 3.36 days; 95% CI, - 5.50 to - 1.22; P = 0.037) and delayed occurrence of OM grade ≥ 2 (95% CI, 0.10 to 0.80; P = 0.017). CONCLUSION: Thyme honey can be considered as a prophylactic agent for OM and decrease the severity of its symptoms. TRIAL REGISTRATIONS: This protocol was registered at the Iranian Registry of Clinical Trials: registration number IRCT201506063106N25, on June 12, 2015; approved by the institutional review board at the Deputy of Research, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran; and approved by the Ethics Committee of Medical Researches of Pharmaceutical Sciences Branch of Islamic Azad University, Tehran, Iran-reference number 5936, on August 17, 2014.

Photobiomodulation for chemotherapy-induced oral mucositis in leukemic children: A randomized controlled clinical trial.

OBJECTIVES: Evaluation of the effectiveness of Photobiomodulation(PBM) for chemotherapy-induced oral mucositis (OM) in leukemic children. MATERIALS AND METHODS: A randomized controlled clinical study including forty-four leukemic children diagnosed with chemotherapy-induced OM at the Hematology/Oncology inpatient unit at Alexandria University Children's Hospital, Alexandria, Egypt. Patients were randomly assigned to either the control or test groups with a 1:1 ratio. The control group received conventional symptomatic treatment, while the test group was treated with PBM in addition to the symptomatic treatment. The response to both treatment modalities was evaluated according to the reduction of pain and lesions severity from baseline to 5, 10, and 14 days after treatment. RESULTS: A significant reduction of pain was recorded on day 10 in the test group compared to the control group (p < 0.001). There was also a significant decline in the OM grades between the two groups on day14 (p = 0.003). No adverse events were reported. CONCLUSIONS: The use of PBM along with the conventional treatment was effective in reducing pain and in the recovery of OM lesions in children receiving chemotherapy for the treatment of ALL. It was also safe and applicable to children.