Chemoradiation-induced Oral Mucositis Research Articles

Intralesional corticosteroid therapy for non-healing persistent radiation-induced oropharyngeal mucositis.

Oropharyngeal mucositis is a common complication of anticancer therapy. This study aimed to determine the effectiveness and safety of intralesional corticosteroid therapy (ICT) in the management of persistent mucositis. A retrospective chart review of patients who underwent ICT in the oral cavity to manage oral mucositis managed with basic oral care and preventive modalities and persisting at least 6 weeks after head and neck radiation or chemoradiation therapy completion between November 2017 and September 2023 was performed. Bio-demographic data, cancer and anticancer therapy characteristics, medical history, and mucositis-related variables were extracted from electronic medical records. Among the 34 participants, 22 (64.7%) were male. Twenty (58.8%) participants received radiotherapy; the rest received chemoradiation therapy. Before the ICT, the median mucositis lesion surface area was 225 mm2 (range 9-2025 mm2), and 22 (64.7%) patients had grade III mucositis. Post-intervention, the median size was reduced to 0 mm2 (range 0-1600 mm2). Clinically effective response (≥ 75% size and symptom reduction) was observed in 28 (82.4%) participants over a median of 26 days (7-60 days). Within this cohort, complete healing of the lesion was seen in 18 (64.3%) subjects. Overall, 25 (73.5%) participants experienced a downgradation in the mucositis stage. Local complications from injections were found in two (5.7%) participants. A correlation was found between clinically effective relief and absence of trismus (p = .03) and smaller pre-procedure surface area (p = .009). The ICT represents a viable option in managing non-healing, persistent radiation, and chemoradiation-induced oral mucositis. The modality was well tolerated and had no systemic complications.

Predictive Factors for Chemoradiation-Induced Oral Mucositis and Dysphagia in Head and Neck Cancer: A Scoping Review

Despite advances in head and neck cancer treatment, virtually all patients experience chemoradiation-induced toxicities. Oral mucositis (OM) and dysphagia are among the most prevalent and have a systemic impact on patients, hampering treatment outcome and harming quality of life. Accurate prediction of severe cases is crucial for improving management strategies and, ultimately, patient outcomes. This scoping review comprehensively maps the reported predictors and critically evaluates the performance, methodology, and reporting of predictive models for these conditions. A total of 174 studies were identified from database searches, with 73 reporting OM predictors, 97 reporting dysphagia predictors, and 4 reporting both OM and dysphagia predictors. These predictors included patient demographics, tumor classification, chemoradiotherapy regimen, radiation dose to organs-at-risk, genetic factors, and results of clinical laboratory tests. Notably, many studies only conducted univariate analysis or focused exclusively on certain predictor types. Among the included studies, numerous predictive models were reported: eight for acute OM, five for acute dysphagia, and nine for late dysphagia. The area under the receiver operating characteristic curve (AUC) ranged between 0.65 and 0.81, 0.60 and 0.82, and 0.70 and 0.85 for acute oral mucositis, acute dysphagia, and late dysphagia predictive models, respectively. Several areas for improvement were identified, including the need for external validation with sufficiently large sample sizes, further standardization of predictor and outcome definitions, and more comprehensive reporting to facilitate reproducibility.

Oxidative Stress and Chemoradiation-Induced Oral Mucositis: A Scoping Review of In Vitro, In Vivo and Clinical Studies.

Chemoradiation-induced mucositis is a debilitating condition of the gastrointestinal tract eventuating from antineoplastic treatment. It is believed to occur primarily due to oxidative stress mechanisms, which generate Reactive Oxygen Species (ROS). The aim of this scoping review was to assess the role of oxidative stress in the development of Oral Mucositis (OM). Studies from the literature, published in MEDLINE and SCOPUS, that evaluated the oxidative stress pathways or antioxidant interventions for OM, were retrieved to elucidate the current understanding of their relationship. Studies failing inclusion criteria were excluded, and those suitable underwent data extraction, using a predefined data extraction table. Eighty-nine articles fulfilled criteria, and these were sub-stratified into models of study (in vitro, in vivo, or clinical) for evaluation. Thirty-five clinical studies evaluated antioxidant interventions on OM’s severity, duration, and pain, amongst other attributes. A number of clinical studies sought to elucidate the protective or therapeutic effects of compounds that had been pre-determined to have antioxidant properties, without directly assessing oxidative stress parameters (these were deemed “indirect evidence”). Forty-seven in vivo studies assessed the capacity of various compounds to prevent OM. Findings were mostly consistent, reporting reduced OM severity associated with a reduction in ROS, malondialdehyde (MDA), myeloperoxidase (MPO), but higher glutathione (GSH) and superoxide dismutase (SOD) activity or expression. Twenty-one in vitro studies assessed potential OM therapeutic interventions. The majority demonstrated successful a reduction in ROS, and in select studies, secondary molecules were assessed to identify the mechanism. In summary, this review highlighted numerous oxidative stress pathways involved in OM pathogenesis, which may inform the development of novel therapeutic targets.

Abstract 6175: 1-Palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol ameliorates chemoradiation-induced oral mucositis in a mouse model by regulating necroptosis

Abstract Background: Currently, no approved drug exist to treat oral mucositis (OM) in patients receiving chemoradiation for the treatment of head and neck cancer. To address this limitation, we examined the therapeutic effect of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG), which is an immune resolution accelerator that can effectively modulate the neutrophil recruitment, against chemoradiation-induced oral mucositis (CRIOM) in a murine model. Additionally, we investigated whether necroptosis is involved in the pathogenesis of CRIOM in a murine model and the therapeutic effect of PLAG against the disease. Methods: To investigate the improved effect of PLAG on CRIOM, we established the CRIOM-bearing BALB/c mouse model using concurrent treatments of 5-fluorouracil (100 mg/kg, i.p.) and X-radiation (20 Gy) on the heads and necks of mice. Phosphate buffer saline or PLAG (100 and 250 mg/kg, p.o.) was administered daily. The body weights of mice were observed daily and on Day 9, the mice were sacrificed for extracting their tongues for further tissue analyses. The histopathological grading of OM was analyzed in the collected tongues. Human keratinocytes (HaCaT) were utilized to identify the mechanism of PLAG on regulating the necroptosis signals. Results: On Day 9, chemoradiotherapy-treated (ChemoRT) mice had tongue ulcerations and experienced significant weight loss (Day 0: 26.18 ± 1.41 g; Day 9: 19.44 ± 3.26 g). They also had elevated serum macrophage inhibitory protein 2 (MIP-2) (control: 5.57 ± 3.49 pg/ml; ChemoRT: 130.14 ± 114.54 pg/ml) and interleukin (IL)-6 (control: 198.25 ± 16.91 pg/ml; ChemoRT: 467.25 ± 108.12 pg/ml) levels. ChemoRT-treated mice who received PLAG exhibited no weight loss (Day 0: 25.78 ± 1.04 g; Day 9: 26.46 ± 1.68 g) and had lower serum MIP-2 (4.42 ± 4.04 pg/ ml) and IL-6 (205.75 ± 30.41 pg/ml) levels than ChemoRT-treated mice without the PLAG treatment. Tongue tissues of mice who received PLAG also displayed lower phosphorylation levels of necroptotic signaling proteins (RIPK1/3 and MLKL). Chemoradiation induced the release of damaged-associated molecular patterns (DAMPs), which activates the necroptosis signaling pathway if not promptly eliminated intracellularly in HaCaT cells. PLAG promoted the effective removal of DAMPs, thereby downregulating the activation of necroptosis signaling pathway. Conclusion: On day 9, the tongues of mice-treated with chemoradiotherapy activated the necroptosis signaling pathway. As a result, cells from oral mucosa released DAMPs and pro-inflammatory cytokines to induce neutrophil migration to the inflamed oral epithelium. PLAG ameliorated the degree of OM by terminating the necroptosis signaling pathway. These data suggest that PLAG may be a useful therapeutic agent for the treatment of CRIOM. Citation Format: Solji Choi, Su-Hyun Shin, Sun Young Yoon, Ji Sun Park, Ki-Young Sohn, Jae Wha Kim. 1-Palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol ameliorates chemoradiation-induced oral mucositis in a mouse model by regulating necroptosis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6175.

1-Palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol ameliorates chemoradiation-induced oral mucositis.

This study was designed to investigate whether necroptosis is involved in the pathogenesis of chemoradiation-induced oral mucositis in a murine model and whether 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) ameliorates this disorder. A chemoradiation-induced oral mucositis model was established by treating mice with concurrent 5-fluorouracil (100mg/kg, i.p.) and head and neck X-irradiation (20Gy). Phosphate-buffered saline or PLAG (100mg/kg or 250mg/kg, p.o.) was administered daily. Body weights were recorded daily, and mice were sacrificed on Day 9 for tongue tissue analysis. On Day 9, chemoradiotherapy-treated (ChemoRT) mice had tongue ulcerations and experienced significant weight loss (Day 0:26.18±1.41g; Day 9:19.44±3.26g). They also had elevated serum macrophage inhibitory protein 2 (MIP-2) (control: 5.57±3.49pg/ml; ChemoRT: 130.14±114.54pg/ml) and interleukin (IL)-6 (control: 198.25±16.91pg/ml; ChemoRT: 467.25±108.12pg/ml) levels. ChemoRT-treated mice who received PLAG exhibited no weight loss (Day 0:25.78±1.04g; Day 9:26.46±1.68g) and had lower serum MIP-2 (4.42±4.04pg/ml) and IL-6 (205.75±30.41pg/ml) levels than ChemoRT-treated mice who did not receive PLAG. Tongue tissues of mice who received PLAG also displayed lower phosphorylation levels of necroptotic signalling proteins. 1-Palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol mitigated chemoradiation-induced oral mucositis by modulating necroptosis.

ANTI-INFLAMMATORY EFFECT OF NIGELLA SATIVA OIL ON CHEMORADIATION-INDUCED ORAL MUCOSITIS IN PATIENTS WITH HEAD AND NECK CANCERS

Objective: Oral mucositis (OM) is a common treatment-induced toxicity in patients undergoing radiation or chemoradiation for head and neck cancers (HNC). The study aims to evaluate the anti-inflammatory effect of Nigella sativa (NS) oil in radiation-or chemoradiation-induced OM in HNC patients.
 Methods: From Forty HNC patients were randomized to two groups, each of 20 patients. The first group was treated with NS oil mouthwash five times daily, while the second group was treated with the Magic mouthwash and served as a control. All patients received radiotherapy (RT) (60-70 Gy) in 30-35 fractions over 6-7 w with or without chemotherapy. Patients were evaluated once per week to estimate the severity and duration of OM and the salivary levels of IL-6 and TNF-α.
 Results: 70% of patients were men and the commonest tumor locations were larynx (47.5%) and pharynx (22.5%) classified as stages III or IV. NS oil significantly reduces RTOG grade and OM severity after 3-4 w of RT, attenuates the elevation in salivary IL-6 and TNF-α production after 3-5 w.
 Conclusion: Nigella sativa oil mouthwash have a potential anti-inflammatory activity that may be beneficial in minimizing or preventing radiation-or chemoradiation-induced oral mucositis in patients with head and neck cancer.

Abstract 4154: 1-Palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) exhibits the therapeutic effect in chemoradiation-induced oral mucositis mouse model

Abstract Oral mucositis is a common complication of chemoradiation therapy and is often accompanied by erythema, ulceration, pain, weight loss. It could delay remission and limit the effectiveness of cancer therapy and increase the risk of infections. However, no specific therapy for protection against mucositis is currently available. In previous study, PLAG (1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol, acetylated diglyceride) was shown to exert a therapeutic effect with pegfilgrastim to treat chemotherapy-induced neutropenia by modulating neutrophil transmigration and chemotherapy-induced megakaryocyte/erythrocyte progenitor decrese was significantly alleviated following PLAG administration. In this study, we investigated the therapeutic effect of PLAG in 5-fluorouracil (5-FU) and radiation-induced oral mucositis mouse model. Following 5-FU (100 mg/kg) injection on Day 0, mice were exposed to whole-body irradiation with 1 Gy gamma-ray radiation on Day 2. In order to facilitate the risk of infection, tongue was scratched 0.2 cm wound at using the tip of an 18-gauge needle at an equal force and depth on Day 4. PLAG was orally administered at 250 mg/kg/day. 5-FU, Radiation and scratching-induced oral mucositis mice exhibited ulceration, fibrosis, and festering wounds. PLAG treatment group decreased ulcer formation and diminished the degree of wound festering form on Day 5. Although CCRT-induce mice declined 16% of body-weight, PLAG only suppressed 2% of body-weight compare to control mice on Day 8. PLAG supported to mouse survival and inhibited mucositis-induced inflammatory responses in the tongue and serum. For head only radiation, custom-made lead shield was used for mice to limit the radiation to the head. After 5-FU (100 mg/kg) injection, mouse's head were received 20 Gy x-ray radiation and PLAG was administrated with 250 mg/kg daily. In toluidine blue (TB) staining, PLAG suppressed concurrent chemoradiotherapy (CCRT)-induced oral mucositis and inflammatory responses. At Day 10, CCRT-induced oral mucositis mice were shown the weight loss and tongue wound festered, and had still not fully recovered and resulted in death. PLAG administration significantly reduced CCRT-induced mucositis and recovered scar better quicker. PLAG also decreased body-weight loss and increased mice survival rate. In histological analysis, CCRT-induced inflammation was recovered in PLAG-treated mice. These data suggest that PLAG enhances recovery from 5-FU/radiation-induced oral mucositis and cachexia. From these data, PLAG could be therapeutically useful in reducing the complications associated with chemotherapy and radiation, and thus may be an excellent supplementary agent for anti-cancer therapy. Citation Format: Ha-Reum Lee, Solji Choi, Kwang Hoon Yang, Do Young Lee, Byoung-Gon Moon, Ki-Young Sohn, Sun Young Yoon, Jae Wha Kim. 1-Palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) exhibits the therapeutic effect in chemoradiation-induced oral mucositis mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4154.

THE EFFICTIVENESS OF LOW LEVEL LASER THERAPY FOR PROVENTION AND TREATMENT OF RADIATION-INDUCEED MUCO

Oral mucositis is the most common and significant complication of chemoradiation therapy for oral and pharyngeal cancer. There are no standard methods for preventing and treating this disease. Patients with severe adverse events need expensive supportive care and unplanned treatment breaks. The objective of the study was to assess and optimize the effectiveness of low level laser therapy (LLLT) for prevention and treatment of chemoradiation-induced oral mucositis in patients with oral and pharyngeal cancer. Material and Methods. Forty-eight patients who received chemoradiation therapy for oral and pharyngeal cancer were enrolled. All patients were randomly divided into two groups. Group I patients (n=28) received standard treatment of chemoradiation-induced complications. Group II patients (n=20) were treated with low level laser therapy (LLLT) at a wavelength of 635 nm, three times a week for three minutes prior to radiation therapy session. Results. In the LLLT group, a statistically significant decrease in the frequency and severity of oral mucositis as well as decrease in pain were observed as compared to the group with standard treatment (χ2 =64,14, р <0,0001). No significant difference in the onset of symptoms and duration of severe mucositis were found. LLLT is an effective method capable of decreasing the frequency and severity of adverse events associated with concurrent chemoradiation therapy.

Randomized control trial of benzydamine HCl versus sodium bicarbonate for prophylaxis of concurrent chemoradiation-induced oral mucositis.

The purpose of the study is to compare the efficacy of benzydamine HCl with sodium bicarbonate in the prevention of concurrent chemoradiation-induced oral mucositis in head and neck cancer patients. Sixty locally advanced head and neck cancer patients treated with high-dose radiotherapy concurrently with platinum-based chemotherapy were randomly assigned to receive either benzydamine HCl or sodium bicarbonate from the first day of treatment to 2weeks after the completion of treatment. The total score for mucositis, based on the Oral Mucositis Assessment Scale (OMAS), was used for the assessment, conducted weekly during the treatment period and at the fourth week of the follow-up. Pain score, all prescribed medications, and tube feeding needs were also recorded and compared. The median of total OMAS score was statistically significant lower in patients who received benzydamine HCl during concurrent chemo-radiotherapy (CCRT) than in those who received sodium bicarbonate, (p value <0.001). There was no difference in median pain score, (p value=0.52). Nineteen percent of patients in sodium bicarbonate arm needed oral antifungal agents whereas none in the benzydamine HCl arm required such medications, (p value=0.06). Tube feeding needs and the compliance of CCRT were not different between the two study arms. For patients undergoing high-dose radiotherapy concurrently with platinum-based chemotherapy, using benzydamine HCl mouthwash as a preventive approach was superior to basic oral care using sodium bicarbonate mouthwash in terms of reducing the severity of oral mucositis and encouraging trend for the less need of oral antifungal drugs.

Comparison of the NCI-CTCAE version 4.0 and version 3.0 in assessing chemoradiation-induced oral mucositis for locally advanced nasopharyngeal carcinoma

To compare the role of CTCAE version 4.0 (v4.0) and version 3.0 (v3.0) in assessing chemoradiation-induced oral mucositis (OM) for locally advanced nasopharyngeal carcinoma (LA-NPC). Patients with LA-NPC were recruited into the study. All eligible participants received docetaxel and cisplatin-based induction chemotherapy followed by intensity modulated radiation therapy concurrent with cisplatin. OM was assessed before and weekly during radiotherapy (RT), using CTCAE v3.0 (clinical exam) and v4.0 separately. OM-related quality of life (QOL) was also evaluated in these patients with the EORTC Quality of Life Questionnaire - Head and Neck module (QLQ-H&N35). From June 2010 to February 2011, 23 eligible patients were enrolled. A highly significant correlation (rho=0.838, p=0.000) and a non-significant difference (p=0.167) in OM grades were found between the two CTCAE versions. However, the trend lines showed that the mean grade determined by CTCAE v3.0 reached a plateau while the mean grade determined by v4.0 continued to increase after the fourth week during RT. Changing trends of several QOL subscale mean scores were similar to that of OM mean grade evaluated by CTCAE v4.0. Both grades of the two CTCAE versions were significantly and positively correlated with scores of several QOL subscales. Nonetheless, the correlation coefficients related to CTCAE v4.0 were higher than those related to v3.0 (rho: 0.727-0.865 versus 0.727-0.778). CTCAE v4.0 could serve as a good surrogate for v3.0 (clinical exam) in assessing chemoradiation-induced oral mucositis. Moreover, CTCAE v4.0 has a few subtle advantages over v3.0 under some circumstances such as delegating QOL. However, there is still no "gold standard" assessment scale for oral mucositis. Therefore, the appropriate tool should be carefully chosen according to the purpose of assessment.

Pharmacological Protection From Radiation ± Cisplatin-Induced Oral Mucositis

To evaluate if two pharmacological agents, Tempol and D-methionine (D-met), are able to prevent oral mucositis in mice after exposure to ionizing radiation ± cisplatin. Female C3H mice, ∼8 weeks old, were irradiated with five fractionated doses ± cisplatin to induce oral mucositis (lingual ulcers). Just before irradiation and chemotherapy, mice were treated, either alone or in combination, with different doses of Tempol (by intraperitoneal [ip] injection or topically, as an oral gel) and D-met (by gavage). Thereafter, mice were sacrificed and tongues were harvested and stained with a solution of Toluidine Blue. Ulcer size and tongue epithelial thickness were measured. Significant lingual ulcers resulted from 5 × 8 Gy radiation fractions, which were enhanced with cisplatin treatment. D-met provided stereospecific partial protection from lingual ulceration after radiation. Tempol, via both routes of administration, provided nearly complete protection from lingual ulceration. D-met plus a suboptimal ip dose of Tempol also provided complete protection. Two fairly simple pharmacological treatments were able to markedly reduce chemoradiation-induced oral mucositis in mice. This proof of concept study suggests that Tempol, alone or in combination with D-met, may be a useful and convenient way to prevent the severe oral mucositis that results from head-and-neck cancer therapy.

Personalized medicine for mucositis: Bayesian networks identify unique gene clusters which predict the response to gamma- d-glutamyl- l-tryptophan (SCV-07) for the attenuation of chemoradiation-induced oral mucositis

Gamma-D-glutamyl-L-tryptophan (SCV-07) demonstrated an overall efficacy signal in ameliorating oral mucositis (OM) in a clinical trial of head and neck cancer patients. However, not all SCV-07-treated subjects responded positively. Here we determined if specific gene clusters could discriminate between subjects who responded to SCV-07 and those who did not. Microarrays were done using peripheral blood RNA obtained at screening and on the last day of radiation from 28 subjects enrolled in the SCV-07 trial. An analytical technique was applied that relied on learned Bayesian networks to identify gene clusters which discriminated between individuals who received SCV-07 and those who received placebo, and which differentiated subjects for whom SCV-07 was an effective OM intervention from those for whom it was not. We identified 107 genes that discriminated SCV-07 responders from non-responders using four models and applied Akaike Information Criteria (AIC) and Bayes Factor (BF) analysis to evaluate predictive accuracy. AIC were superior to BF: the accuracy of predicting placebo vs. treatment was 78% using BF, but 91% using the AIC score. Our ability to differentiate responders from non-responders using the AIC score was dramatic and ranged from 93% to 100% depending on the dataset that was evaluated. Predictive Bayesian networks were identified and functional cluster analyses were performed. A specific 10 gene cluster was a critical contributor to the predictability of the dataset. Our results demonstrate proof of concept in which the application of a genomics-based analytical paradigm was capable of discriminating responders and non-responders for an OM intervention.

Management of oral mucositis in patients with head and neck cancer receiving chemoradiotherapy and/or molecular targeted therapy

To investigate the prevalence and treatment of oral mucositis caused by concurrent chemoradiotherapy and/or molecular targeted therapy in the patients with advanced squamous cell carcinoma of the head and neck. A retrospective study of the incidence and treatment of oral mucositis was performed in 179 patients (155 male and 24 female;124 patients at stage III and 55 patients at stage IV) receiving concurrent chemotherapy and (or) molecular targeted therapy between November 2007 and November 2010. Grade I, II, III and IV oral mucositis occurred respectively in 49, 50, 67 and 13 patients. All the patients received oral mucositis prophylaxis. After the occurrence of oral mucositis, conventional treatment of mucositis combined with quinolone antibiotics were applied. Of the patients, 99 patients with grade I or II and 4 patients with grade III oral mucositis were effectively managed by conventional treatment; 76 patients with grade III or IV oral mucositis were also significantly controled by conventional treatment plus antibiotics. After the treatments, all patients with oral mucositis were under control, with the decrease in the grade of oral mucositis, the reduction of oral pain and the improvement in ability to eat. None of them had radiation treatment breaks. Combined modality therapy can effectively control chemoradiation-induced oral mucositis in patients with head and neck squamous cell carcinoma, grade I and II oral mucositis were cured by conventional treatment and quinolone antibiotics play a key role in the treatments for grade III and IV oral mucositis.

Prophylactic Low-energy Laser Application to Prevent Chemoradiation-induced Oral Mucositis: A Prospective and Randomized Trial

Prophylactic Low-energy Laser Application to Prevent Chemoradiation-induced Oral Mucositis: A Prospective and Randomized Trial

A Randomised, Double-Blind, Parallel, Placebo-Controlled Study to??Evaluate the Efficacy of MF 5232 (Mucotrol???), a Concentrated Oral Gel??Wafer, in the Treatment of Oral Mucositis

Oral mucositis is a major complication of cytotoxic chemotherapy and radiotherapy associated with significant morbidity, pain, odynophagia, dysgeusia and subsequent dehydration and malnutrition, and effective prophylaxis and/or treatment of this condition is essential. The currently available palliative treatment shows improvement only in patients with mild to moderate mucositis. The primary aim of this study was to compare the clinical efficacy of MF 5232 (Mucotrol), a concentrated oral polyherbal gel wafer formulation, with placebo in the management of chemoradiation-induced mucositis in cancer patients. In this randomised, double-blind, pilot study a total of 30 patients of either sex with chemoradiation-induced oral mucositis were randomised to receive MF 5232 (n = 15) or a matching placebo (n = 15) after food three times a day for 7-10 days. Patients were evaluated using validated and standardised scoring systems at baseline and after 7-10 days of treatment. There were 11 evaluable patients in each treatment group. There was a significant reduction in mean mucositis scores with MF 5232 as follows: WHO (from 3.0 to 1.8), Radiation Therapy Oncology Group (gross score: from 2.8 to 1.8; functional score: from 2.9 to 1.0), and Objective Scoring System (ulceration score: from 7.4 to 4.4; erythema score: from 13.7 to 7.0). There were no significant changes in scores for placebo recipients. The treatments were well tolerated, with the exception of two patients in the treatment group who reported a burning sensation in the mouth after dissolving the wafer. This pilot study provided positive evidence for the efficacy of MF 5232 therapy in chemoradiation-induced mucositis. This was probably a result of its local analgesic, antioxidant and immunomodulatory activity and wound-healing properties. Further in-depth analysis in a larger number of patients is required to confirm these positive results.