Oral Mucositis Pain Research Articles

Effect of bupivacaine lozenges on oral mucositis pain: a randomized controlled multicenter phase II study.

A nonblinded parallel-group randomized controlled study investigated the efficacy and tolerability of repeated administration of a bupivacaine lozenge (25 mg) as pain management for oral mucositis pain in head and neck cancer patients as add-on to standard systemic pain management. The primary end point was the difference between the intervention group (Lozenge group) and the Control group in daily mean pain scores in the oral cavity or pharynx (whichever was higher). Fifty patients from 2 hospitals in Denmark were randomized 1:1 to 7 days of treatment with bupivacaine lozenges (taken up to every 2 hours) plus standard pain treatment minus topical lidocaine (Lozenge group) or standard pain treatment including topical lidocaine (Control group). The efficacy analysis included 38 patients, as 12 patients were excluded because of changes in study design and missing data. Mean pain in the oral cavity or pharynx (whichever was higher) was significantly lower 60 minutes after taking lozenges (35 mm [n = 22]) than for the Control group (51 mm [n = 16]) (difference between groups -16 mm, 95% confidence interval: -26 to -6, P = 0.0032). Pain in the oral cavity was also significantly lower in the Lozenge group (18 mm) vs the Control group (36 mm, P = 0.0002). Pharyngeal mucositis pain did not differ significantly (37 mm [Lozenge group] vs 48 mm [Control group], P = 0.0630). No serious adverse events were reported. These results show that the bupivacaine lozenge as an add-on to standard pain treatment had a clinically significant pain-relieving effect in patients with oral mucositis. NCT02252926.

Preliminary study in a new protocol for the treatment of oral mucositis in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT) and chemotherapy (CT)

Oral mucositis (OM) is a debilitating and serious side effect in patients undergoing hematopoietic stem cell transplantation (HSCT) and chemotherapy (CT). Laser therapy is becoming a promising treatment option in these patients, avoiding the necessity of enteral/parenteral nutrition. The aim of this study was to evaluate the efficacy of laser therapy in patients affected by oral mucositis induced by chemotherapy and HSCT. Sixteen onco-hematological pediatric patients receiving chemotherapy and hematopoietic stem cell transplantation, affected by oral mucositis, were enrolled in this study. They were divided in two randomized groups: the laser group and the placebo-control group. Patients in the laser group were treated with HPLT (970±15nm, 3.2W (50%), 35-6000Hz, 240s) for four consecutive days, once a day; and placebo group underwent sham treatment. The assessment of mucositis was recorded through WHO Oral Mucositis Grading Objective Scale, and pain was evaluated through Visual Analogue Scale (VAS). Patients were monitored and evaluated 3, 7, and 11days after the first day of laser therapy. Once OM was diagnosed, the patients had mucositis grading assessments before laser or sham application at day 3, 7, and 11 after first application. All patients of laser group demonstrated improvement in pain sensation from day 3 after first application of laser (p<0.05), ulcerations reduced their dimensions and erythema disappeared. The patients of placebo group had improvement from day 7. In laser group, all mucositis were fully resolved from day 7 (p<0.05). Oral mucositis negatively impacts on nutritional intake, oral hygiene, and quality of life. Laser therapy appears to be a safe and innovative approach in the management of oral mucositis. In this preliminary study, HPLT encourages to consider laser therapy as a part of onco-hematological protocol, providing to decrease pain and duration of OM induced by CT and HSCT. Further researches will be needed, especially randomized, controlled clinical trials with a large number of enrolled patients and a long term of follow-up to confirm the efficacy of laser therapy in prevention and control of OM in onco-hematological pediatric patients.

Methylene Blue for the Treatment of Intractable Pain Associated with Oral Mucositis.

Oral mucositis is a common and often debilitating complication among cancer patients receiving radiation therapy to the head and neck or chemotherapy agents, or undergoing hematopoietic stem cell transplantation. Pain and decreased oral function associated with oral mucositis may persist long after the conclusion of therapy. Although most patients respond to conservative management, a subset of patients develops intractable pain with severe consequences. For some, the use of total parenteral nutrition with insertion of percutaneous endoscopic gastrostomy feeding tubes is the only alternative. Current recommendations to treat mucositis and its related pain include basic oral care, bland oral rinses, topical anesthetics, and systemic analgesics. We believe that chemical neurolysis of the affected areas with methylene blue used as an oral rinse is a noninvasive, efficient, safe, and cost-effective alternative that can provide prolonged analgesia in patients with intractable pain of oral mucositis. The benefits of this therapy are reflected in its improvement of patients' quality of life by enabling oral feeding and controlling pain. We report a series of 5 consecutive patients with intractable oral mucositis-related pain despite conventional treatment with systemic opiates. All 5 patients responded well to the use of 0.05% methylene blue as mouth rinse, demonstrating sustained analgesia over 3 weeks. The treatment was tolerated well, and overall patient satisfaction was very high. We also observed that methylene blue rinse significantly reduced the total opioid requirement, as demonstrated by reductions in the patients' morphine equivalent daily dose scores after its use. Our case series suggests that 0.5% methylene blue oral rinse therapy is an effective and inexpensive modality that can be used safely to palliate intractable oral pain in patients with mucositis associated with cancer treatment. To our knowledge, this is the first report using this therapy to treat pain from oral mucositis.

Pain management for chemotherapy-induced oral mucositis.

The number of children and young people diagnosed with cancer is increasing every year. Pain is a significant side effect of disease, surgery and treatments including chemotherapy. After a course of intensive chemotherapy, some children develop oral mucositis, a debilitating condition causing bleeding, pain and inflammation. Moderate and severe mucositis pain is treated with continued good oral hygiene and parenteral analgesia. The aim of this article is to identify challenges in managing chemotherapy-induced oral mucositis pain in children, and to highlight the benefits of adding ketamine as an adjuvant analgesic. A small number of studies and case reports in children have examined ketamine for cancer pain and have demonstrated its successful use in the treatment of chronic pain conditions. However, there remtains a paucity of data about the efficacy of continuous low dose ketamine administration in children with cancer. Further studies are required to establish its benefits to support the addition of ketamine to the World Health Organization's analgesic ladder.

Role of Gabapentin in Managing Mucositis Pain in Patients Undergoing Radiation Therapy to the Head and Neck

Oral mucositis (OM) is a painful and debilitating side effect that affects 80%-100% of patients undergoing radiation therapy for head and neck cancer. This dose-limiting side effect may potentially lead to pain, dehydration, malnutrition, infection, and treatment breaks. Treatment breaks can lead to decreased disease control and suboptimal patient outcomes. No primary prevention exists for OM, and management is focused on pain control. Compelling evidence exists that OM pain has somatic and neuropathic components. This article reviews the existing literature on the use of gabapentin (Neurontin®) as a co-analgesic in treating the neuropathic pain in OM. A literature search was performed using CINAHL® and PubMed with the search terms gabapentin and oral mucositis. The selected articles were briefly screened for relevance, and three were included in this review. No systematic reviews exist on the role of gabapentin for neuropathic pain in radiation-induced OM. Two retrospective studies concluded that gabapentin reduced escalation of opioid doses and unplanned treatment breaks. One retrospective study demonstrated favorable swallowing outcomes. Pain and OM are nursing-sensitive outcomes that can be significantly affected by evidence-based nursing interventions.

A Phase III, Randomized Double-Blind Study of Doxepin Rinse versus Magic Mouthwash versus Placebo in the Treatment of Acute Oral Mucositis Pain in Patients Receiving Head and Neck Radiotherapy with or without Chemotherapy (Alliance A221304)

A Phase III, Randomized Double-Blind Study of Doxepin Rinse versus Magic Mouthwash versus Placebo in the Treatment of Acute Oral Mucositis Pain in Patients Receiving Head and Neck Radiotherapy with or without Chemotherapy (Alliance A221304)

A novel lozenge containing bupivacaine as topical alleviation of oral mucositis pain in patients with head and neck cancer: a pilot study.

Introduction: Oral mucositis induces severe oral pain in head and neck cancer patients. There is at this point no effective pain treatment without considerable side effects.Objective: The aim of this pilot study was to investigate pain reduction in oral cavity and pharynx in patients with head and neck cancer (HNC) with oral mucositis, the location of anesthetic effect, and duration of pain relief, after a single-dose administration of a 25 mg bupivacaine lozenge.Methods: Ten patients with HNC suffering from oral mucositis pain were included. The patients assessed pain in the oral cavity and pharynx on a visual analogue scale (from 0 to 100 mm) at baseline and up to 3 hours after the lozenge was dissolved. Possible adverse events were registered.Results: The baseline pain was 51 mm (range: 30–73 mm) in the oral cavity and 58 mm (range: 35–70 mm) in the pharynx. When the lozenge was dissolved, both oral (−27 mm; range: −3 to −52 mm; P = 0.0003) and pharynx pain (−20 mm; range: −3 to −45 mm; P = 0.008) were significantly reduced. After 180 minutes, the mean reduction in pain was significant in the oral cavity (−18 mm; range: −8 to −30 mm; P < 0.0001) but not in the pharynx (−8 mm; range: +4 to −23 mm; P = 0.12). No adverse events were observed.Conclusion: The results indicate that the bupivacaine lozenge has a clinically significant and long-lasting pain-relieving effect on pain because of oral mucositis in patients with HNC.

R11 - Mucositis pain: treatment pptions for the patient

Background: Oral mucositis (OM) is the most frequent complication deriving from oncology treatment, causing pain of the oral cavity and dysphagia that greatly compromise the patient's quality of life. Under-treated pain of OM, can lead to malnutrition, weight-loss, astenia and emotional stress. Therefore, swift, effective symptom-management of OM is of vital importance. Analgesic therapy is often inappropriate or ineffective, whereas opiates such as Morphine are available only to a limited number of patients. Moreover, the difficulty in executing multicentric studies on narcotic drugs makes for a very grim scenario indeed. Morphine is still considered the number one drug of choice for moderate to severe oncological pain, according to EAPC (European Association for Palliative Care). However, Morphine is not generally administered for the treatment of OM pain. The objective of this article is to assess the efficacy of analgesic therapy administered during cancer treatment with specific regard to OM. Materials (patients) and methods: Assessment of pain intensity of OM during oncology treatment in patients of the National Tumor Institute of Milan. Results: Of the 150 subjects with OM in relation to various regimes of oncology treatment, 138 referred oral cavity pain of differing intensity. Data analysis revealed that 58% (88 subjects) referred oral-pharyngeal pain (NRS 5 or more) that was uncontrolled, and 27% of the same group (41 patients) received no pain mediction. Of the 52 patients that referred severe pain (NRS 7-10), 42%, (22 subjects) used no pain medication while only 19%, (10 subjects) received strong, IV opiates. Conclusions: OM pain receives little consideration, hence inadequate treatment, negtively influencing the patient's quality of life. The WHO Assessment Scale most utilized for confirming OM is not specific for identifying pain intensity of the oral cavity. Despite the fact that Morphine is considered one of the drugs of choice for oncological pain, it is not generally administered as treatment for moderate/severe OM. Proper use of specific assessment tools, identification of the most appropriate treatment for pain relief for OM as well as reference to common guidelines would greatly assist in resolving the issue so that patients may continue oncology treatment, unhindered by complications deriving from OM.

Chronic oral mucositis after radiotherapy to the head and neck: a new insight.

Oral mucositis is a major complication of anticancer therapy yet the literature focuses on immediate (acute) mucosal changes and hardly describes the chronic form. We aim to report the clinical manifestations of chronic mucositis. A retrospective chart review of oral mucositis referrals was performed. Inclusion/exclusion criteria defined the patients that were considered to have chronic mucositis. Four female patients treated for tongue/lower lip squamous cell carcinoma were included. Extensive painful oral mucositis lesions developed in all patients during the course of radiotherapy, with ulcers remaining for 5-24months after completion of therapy. We describe two presentations, namely the persistent form (long-lasting ulcers continuing from acute ulcers) and the recurrent form (new discrete ulcers appearing on atrophic mucosa following the completion of radiotherapy). The long-term oral complications of radiotherapy to the head and neck may include chronic atrophic, erythematous, and/or ulcerated lesions. A diagnosis of chronic oral mucositis should be considered when the lesions are observed at least 3months after radiotherapy, and other possible etiologies have been excluded. The influence of age and comorbidities (primarily diabetes mellitus) on chronic mucositis, the significance to patient's quality of life, and the management of chronic mucositis are important subjects for future research.

Treatment of Radiation-Induced Oral Mucositis Using a Novel Accepted Taste of Prolonged Release Mucoadhesive Bi-medicated Double-Layer Buccal Films.

The aim of this study was to develop a novel double-layer bi-medicated prolonged release mucoadhesive buccal film (MBF) containing lidocaine hydrochloride (LC) and diclofenac potassium (DK). The ultimate goal of the prepared system is the treatment of radiation-induced oral mucositis pain with improved patient acceptance. MBFs were prepared using 3 × 22 randomized full factorial design for film optimization. Nanoemulsion system (NES) was used to mask DK bitter taste. The prepared films were characterized, viz thickness, mass uniformity, surface pH, folding endurance, swelling studies, ex vivo bioadhesive strength, in vitro drug release, and ex vivo permeation. The in vivo evaluation was carried out by testing the anti-inflammatory and analgesic activities on rats followed by a clinical study on patients to prove their acceptance. The optimized MBF composed of 10% w/w HPMC-4KM, 50mg LC, and 50mg DK-NES was selected due to prolonged in vitro drug release pattern and ex vivo permeability (95.24 ± 2.14 and 93.48 ± 3.24% in 6h, respectively). MBF exposed a strong anti-inflammatory effect from 61 to 87% inhibition with a strong analgesic effect when compared to DK® and LC®, respectively. The clinical study revealed that films were accepted by the patients, and the presence of LC on the outer side helped in pain feeling reduction while DK-NES in the inner side facilitated in rapidly relieving the inflammation effect.

Doxepin for Radiation Therapy-Induced Mucositis Pain in the Treatment of Oral Cancers.

Radiotherapy (RT), an integral part of the oncologic treatment for patients with head and neck cancer, can cause adverse side effects such as oral mucositis (OM). Pain from OM can impact a patient’s quality of life and interrupt RT treatment schedules, which decreases the probability for achieving cancer cure. Conventionally, RT-induced OM pain is treated with analgesics and/or mouthwash rinses. Doxepin, a traditional tricyclic antidepressant with analgesic and anesthetic properties when applied topically to the mucosa, has been shown to lower OM pain in multiple single-arm trials (Epstein et al.) and more recently, in a placebo-controlled crossover study (Leenstra and Miller et al.). Currently, a placebo-controlled study (Sio and Miller et al.) using doxepin for esophagitis pain caused by RT to the thorax is underway. Doxepin will also be further compared with magic mouthwash and a placebo solution in a three-arm trial (Miller and Sio et al.) with head and neck cancer patients with OM pain caused by RT. Doxepin may represent a new standard for treating RT-induced OM pain in the future.

Professional oral health care reduces oral mucositis pain in patients treated by superselective intra-arterial chemotherapy concurrent with radiotherapy for oral cancer.

Oral mucositis (OM) is a painful complication of radiation therapy (RT) for head and neck cancer. OM can compromise nutrition, require opioid analgesics and hospitalization for pain control, and lead to interruption of treatment. Severe oral mucositis appears inevitable in superselective intra-arterial chemotherapy concurrent with radiotherapy (SSIACRT), requiring management of OM for the patient. The objective of this study was to assess the utility of professional oral health care (POHC) for the management of OM in patients undergoing SSIACRT. Thirty-three patients were enrolled in this study. The first 17 patients underwent SSIACRT before we created an oral management team, and thus did not receive POHC. The remaining 16 patients received POHC. Fever duration, duration of oral feeding difficulty, opioid usage, duration of opioid administration, duration of hospitalization, and number of hospital days from the end of irradiation to discharge were compared between these two groups. Median total dose of morphine during SSIACRT, median number of hospital days from end of irradiation to discharge, and duration of hospitalization all differed significantly between groups (P < 0.05). Duration of opioid administration, fever duration, and duration of oral feeding difficulty did not differ significantly between groups. These findings indicate that POHC may reduce opioid use and shorten the hospital stay. Such results might be obtained through infection control by POHC. This report appears to be the first study to evaluate the efficiency of POHC in SSIACRT for oral cancer from the perspective of mucositis pain and opioid use.

Mineral derivatives in alleviating oral mucositis during cancer therapy: a systematic review.

Objectives. Oral mucositis (mouth ulcers) is a cancer therapy side effect. Costly treatment interventions are often neglected in favor of cost-effective agents. This review assessed the general efficacy of mineral derivatives (a cost-effective agent) in alleviating oral mucositis (OM) during cancer therapy compared to the standard care, or placebo—including a decision tree to aide healthcare workers.Data Sources. Electronic searches of MEDLINE via OVID, EMBASE, CENTRAL, CANCERLIT via PubMed, and CINAHL via EBSCO (year 2000 to 11 September 2014) were undertaken for randomised controlled trials. A meta-search strategy extracted content from aggregate online databases.Review Methods. Randomized controlled trials were assessed (participants, intervention, outcome, results, and risk of bias) for inclusion. The author abstracted binary and continuous data synthesised to Hedges’ g in a random effects model. The primary outcome measures were severity (incidence of peak oral mucositis, duration of oral mucositis, and time to onset); secondary outcome measures were the incidence of pain, and analgesic use. Serum mineral levels, total parenteral nutrition, and adverse events were discussed. The decision tree was mapped using sensitivity, specificity, pre-test and post-test Bayesian probability.Results. 1027 citations were identified and 16 studies were included (n = 1120; mean age 49 years). Cancer therapies consisted of chemotherapy, radiotherapy, chemo-radiotherapy, or hematopoietic stem cell transplantation. Outcome mineral derivatives were zinc (n = 549), calcium phosphate (n = 227), povidone-iodine (n = 228), or selenium (n = 116). Severity was measured across variable OM grading systems: In 13 studies, individuals in treatment groups (n = 958) experienced peak OM less than controls (g = −0.47, 95% CI −0.7 to −0.2, p = 0.0006); time to OM onset was significantly delayed in treatment than controls (g = −0.51, 95% CI−0.8 to −0.2, p = 0.0002; five studies); OM mean duration, pain incidences, or analgesics use was not significant. The decision analysis favored selenium.Conclusion. The general positive effect trend suggests individuals taking mineral derivatives during cancer therapies are less likely to experience peak OM than those without. However, significant bias and heterogeneity indicates the need for developing further methods in account of diverse protocols and include novel recordings (serum mineral levels and cell signals) in estimating a uniform true effect.

Low level laser therapy against radiation induced oral mucositis in elderly head and neck cancer patients-a randomized placebo controlled trial

ObjectivesRadiotherapy (RT) is treatment of choice for Elderly Head and Neck Cancer (HNC) patients. Oral mucositis (OM) during RT affects patient’s routine oral activities and overall health. Low Level Laser Therapy (LLLT) provided some promising results against cancer therapy induced OM in children and adults. No study specifically evaluated effects of LLLT against RT induced OM in elderly HNC patients until date, hence we did this study. Material and methodsThis double blinded study randomized 46 elderly HNC patients scheduled for RT [Dosage=66 Gray (2Gy/fraction), 5 fractions/week, total 33 fractions for 6.5weeks], into laser (22) and placebo (24) groups. Laser group patients received LLLT [Helium–Neon, λ=632.8nm, power density=0.024W/cm2, dosage=3.0J/point at six anatomical sites bilaterally i.e. 12 locations, total dose/session=36J, beam aperture diameter=0.6mm, beam spot size=1cm2, irradiated area diameter=1cm2, irradiation time/point=125s, 5 sessions/week, non-contact method-distance between probe and irradiated tissues <1cm, whereas placebo group did not receive laser. OM grades (RTOG/EORTC Scale), oral pain, weight loss, need for morphine analgesics and tube feeding, and RT break were recorded by a blinded assessor. Descriptive statistics and repeated measures ANOVA were used for analysis keeping p<0.05. ResultsSignificant reduction in the incidence and duration of severe OM (p=0.016) and severe pain (p=0.023) and weight loss (p=0.004) was observed in laser than placebo group. No difference was found for enteral feeding use (p=0.667) between two groups. ConclusionsLLLT decreased the severity of OM and oral pain in elderly HNC patients. Also, lesser weight loss, morphine analgesic use and radiation break happened in laser group.

Doxepin Rinse Versus Placebo in the Treatment of Acute Oral Mucositis Pain in Patients Receiving Head and Neck Radiotherapy With or Without Chemotherapy: A Phase III, Randomized, Double-Blind Trial (NCCTG-N09C6 [Alliance

Painful oral mucositis (OM) is a significant toxicity during radiotherapy for head and neck cancers. The aim of this randomized, double-blind, placebo-controlled trial was to test the efficacy of doxepin hydrochloride in the reduction of radiotherapy-induced OM pain. In all, 155 patients were randomly allocated to a doxepin oral rinse or a placebo for the treatment of radiotherapy-related OM pain. Patients received a single dose of doxepin or placebo on day 1 and then crossed over to receive the opposite agent on a subsequent day. Pain questionnaires were administered at baseline and at 5, 15, 30, 60, 120, and 240 minutes. Patients were then given the option to continue doxepin. The primary end point was pain reduction as measured by the area under the curve (AUC) of the pain scale using data from day 1. Primary end point analysis revealed that the AUC for mouth and throat pain reduction was greater for doxepin (-9.1) than for placebo (-4.7; P < .001). Crossover analysis of patients completing both phases confirmed that patients experienced greater mouth and throat pain reduction with doxepin (intrapatient changes of 4.1 for doxepin-placebo arm and -2.8 for placebo-doxepin arm; P < .001). Doxepin was associated with more stinging or burning, unpleasant taste, and greater drowsiness than the placebo rinse. More patients receiving doxepin expressed a desire to continue treatment than did patients with placebo after completion of each of the randomized phases of the study. A doxepin rinse diminishes OM pain. Further studies are warranted to determine its role in the management of OM.

Treatment of oral mucositis pain following radiation therapy for head-and-neck cancer using a bioadhesive barrier-forming lipid solution

PurposeCAM2028, a vehicle that forms a bioadhesive lipid barrier when applied to the oral mucosa, was developed as a carrier system for local delivery of benzydamine, an NSAID used for pain relief in oral mucositis. This trial compared the analgesic effect of CAM2028 plus benzydamine (CAM2028-benzydamine) with unmedicated CAM2028 (CAM2028-control) for the treatment of oral mucositis in patients with head-and-neck cancer.MethodsThirty-eight study participants were enrolled during their 3rd to 4th week of radiation therapy. Participants were required to have symptomatic oral mucositis (WHO Grade 2 or above) at screening and pain scores of at least 6 on an 11-point Likert scale at screening and on each day before treatment with study medication. After undergoing radiation, patients were administered a single dose of CAM2028-control or CAM2028-benzydamine 2 days apart, in a randomized crossover fashion. Pain was assessed over the following 8 h.ResultsWith both treatments, patients experienced a mean 40 % decrease in pain intensity at 6 h (the primary study endpoint). Both treatments resulted in significant pain relief within 5 min of application that was evident during the entire 8-h assessment period. There was no difference in pain relief between the two interventions at any time point. Both treatments were safe and well tolerated.ConclusionsCAM2028-benzydamine and CAM2028-control were both efficacious in reducing pain in patients with oral mucositis related to radiation therapy for head-and-neck cancer. Analgesic effects of both medications were immediate, clinically significant, and persistent for up to 8 h.

A Comparative Study to Assess the Effectiveness of Turmeric Mouth Wash versus Saline Mouth Wash on Treatment Induced Oral Mucositis (Tiom) in a Selected Hospital at Mangalore

Oral mucositis is the most common, debilitating complication of cancer treatments. Chemotherapy and/or radiation therapy will interfere with the normal turnover of epithelial, cells leading to mucosal injury. The care of these patients includes the regular use of an effective mouth wash periodically. The active ingredient in turmeric is curcumin which protects healthy cells from harmful effects of radiation and chemotherapy. Salt mouthwash can soothe the pain and keep food particles clear so as to avoid infection. The study made use of a two group pre-test post-test time series design to determine the effectiveness of Turmeric and Saline mouth wash on TIOM. A purposive random sampling was used and mouth wash was given three times daily for 5 days. The oral mucosa of the patients was assessed using an Oral Mucositis assessment checklist and pain using pain scale every morning before the intervention and evening after the intervention. There was a significant difference in the score of TIOM between pre-intervention on Day 1 morning and post intervention score on day 5 evening in turmeric and saline group but on comparison it was found that turmeric mouth wash was effective than saline mouth in all the days except in Day 3 where there was no significant difference found. Both the mouth wash were individually effective but on comparison turmeric mouth wash was better than saline mouth wash.

Oral microbiota: An overlooked etiology for chemotherapy-induced oral mucositis?

Oral mucositis, characterized by inflammatory response and cell loss in the epithelial cells lining of the oral cavity, is one of the most debilitating adverse effects of chemotherapy. In patients undergoing high-dose myeloablative therapies, the incidence rate of oral mucositis is almost 100%, and in cancer patients undergoing standard-dose chemotherapy the rate is 40e60%. Chemotherapeutic agents with pronounced stomatotoxic effects are listed in Table 1. Pain, odynophagia, dysguesia, and subsequent malnutrition of oral mucositis have become a common reason for decreasing the dosages of antineoplastic agents, necessitating deference or cessation of antineoplastic treatments, and preventing patients from optimal chemotherapy regimens, ultimately leading to higher mortality in cancer patients. In addition, a vast variety of microorganisms including bacteria, fungi, and viruses in the oral cavity may enter the bloodstream because of the loss of mucosal integrity, leading to systemic infections that interrupt antineoplastic treatments, or even jeopardize patients’ lives. Historically, chemotherapy-induced mucositis was thought to occur solely because of the basal cell damage of the epithelium when drugs permeate into these cells via

Low-level laser therapy can produce increased aggressiveness of dysplastic and oral cancer cell lines by modulation of Akt/mTOR signaling pathway.

Low-level laser therapy (LLLT) is a non-thermal phototherapy used in several medical applications, including wound healing, reduction of pain and amelioration of oral mucositis. Nevertheless, the effects of LLLT upon cancer or dysplastic cells have been so far poorly studied. Head and neck cancer patients receiving LLLT for oral mucositis, for example, might have remaining tumor cells that could be stimulated by LLLT. This study demonstrated that LLLT (GaAlAs--660 nm or 780 nm, 40 mW, 2.05, 3.07 or 6.15 J/cm²) can modify oral dysplastic cells (DOK) and oral cancer cells (SCC9 and SCC25) growth by modulating the Akt/mTOR/CyclinD1 signaling pathway; LLLT significantly modified the expression of proteins related to progression and invasion in all the cell lines, and could aggravate oral cancer cellular behavior, increasing the expression of pAkt, pS6 and Cyclin D1 proteins and producing an aggressive Hsp90 isoform. Apoptosis was detected for SCC25 and was related to pAkt levels.

N09C6 (Alliance) - A Phase 3, Randomized Double-Blind Study of Doxepin Rinse Versus Placebo in the Treatment of Acute Oral Mucositis Pain in Patients Receiving Head and Neck Radiation Therapy With or Without Chemotherapy

Oral mucositis (OM) remains a significant toxicity in patients receiving radiotherapy (RT) for malignancies of the head and neck (H&N). Previous pilot research has suggested that doxepin, a tricyclic antidepressant, reduces RT induced OM when used as a mouth rinse.