Treatment Of Chemotherapy-induced Mucositis Research Articles

Nonpharmacological approaches for improving gut resilience to chemotherapy.

Mucositis of the gastrointestinal tract is a debilitating side effect of chemotherapy that negatively influences treatment tolerance and patient life quality. This review will evaluate the recent literature on nonpharmacological strategies that have the potential to improve chemotherapy-induced mucositis (CIM). Alternatives to pharmacological approaches have shown great promise in preventing CIM. Natural products, including curcumin, ginseng, quercetin, and patchouli all show potential in mitigating CIM. In addition, dietary patterns, such as the elemental diet, high fiber diet, and diets high in amino acids have documented benefits in preventing CIM. Perhaps the greatest advancement coming to this arena in recent years is in the field of probiotics. Indeed, research on single species as well as probiotic mixtures show potential in reducing CIM insofar as probiotics are now being suggested for treatment of CIM by governing bodies. Although behavioral interventions including psychological interventions and exercise interventions have shown promise in reducing cancer therapy-related side effects, more work in this domain is warranted and particularly in the context of CIM. Alternatives to pharmacological approaches show great potential for use in prevention and treatment of CIM and should be further developed for use in the clinic.

ANTIMICROBIAL PHOTODYNAMIC THERAPY ON ORAL MUCOSITIS: A PILOT STUDY

Objective To evaluate the effect of antimicrobial photodynamic therapy (PDTa) on the treatment of chemotherapy-induced mucositis in pediatric patients. Study Design It was a pilot study of an open, controlled, and blind randomized clinical trial conducted with 29 patients, with ages ranging from 10 months to 18 years, who were divided into 2 groups. Group A was submitted to PDTa with 0.01% methylene blue and red laser with 3 J energy per point; group B was submitted to photobiomodulation with wavelength of 660 nm and 1 J energy per point. The chi-square, Fisher exact, Student's t, and Mann-Whitney tests and the mixed linear regression model were used for comparison between the groups, with the maximum error admitted of 5%. Results There was no difference between the groups regarding the number of sessions necessary for clinical cure of the oral lesions (P = .95) or reduction in pain (P = .26; P = .49). Within each group, however, there was significant reduction in pain (P = .03; P = .003). Conclusion PDTa could be used for control of oral mucositis in children/young patients. It was well tolerated and presented satisfactory results, the same as photobiomodulation in reducing pain associated with the mucositis.

Effect of epigallocatechin-3-gallate from green tea on 5-flurouracil-induced intestinal mucositis.

522 Background: Chemotherapy-induced mucositis is a common complication during anticancer treatment. Epigallocatechin-3-gallate (EGCG), derived from green tea, has been shown to have antioxidant effects and immunomodulatory activities. However, studies on EGCG for chemotherapy-induced mucositis have been scarce. In this study, we aimed to prove the protective effect of EGCG in murine chemotherapy-induced mucositis model Methods: Twenty-four 8-wk-old male C57BL/6 mice were randomized to 4 groups : control, EGCG, 5-Flurouracil (5-FU), EGCG plus 5-FU. Mucositis was induced by intraperitoneal injection of 5-FU (400mg/kg). EGCG (50mg/kg) was administered orally for 5 days from the day before administration of 5-FU. After 6 days of 5-FU injection, the mice were sacrificed and intestinal tissue was obtained. WBC count was performed with whole blood from Inferior vena cava of mice. The end points were villus height, villus/crypt ratio, histologic characteristics, and mRNA expression of tumor necrosis factor ( TNF)-α, and interleukin ( IL)-6. Results: In 5-FU group, neutropenia was confirmed by laboratory test (5-FU, 0.650 K/μL; Control, 5.317 K/μL), indicating sufficient 5-FU effect. Histologic findings showed that crypt dilatation, villus stunting, and villus atrophy were reduced in EGCG plus 5-FU group than in 5-FU group. Quantitatively, mean villus height (EGCG plus 5-FU, 352 μm; 5-FU, 319 μm) and villus/crypt ratio (EGCG plus 5-FU, 3.28; 5-FU, 2.31) in EGCG plus 5-FU group, compared with 5-FU treated group, were significantly higher. mRNA expression of TNF-α was significantly lower in EGCG plus 5-FU group compared with 5-FU group (P < 0.05) (Figure 2). Conclusions: EGCG derived from green tea reduced 5-FU induced intestinal mucositis, suggesting a possibility for novel treatment of chemotherapy-induced mucositis.

Global Health Journal Club: Is Honey Effective as a Treatment for Chemotherapy-induced Mucositis in Paediatric Oncology Patients?

Oral mucositis (OM) is an inflammatory response of mucosal epithelium to the cytotoxic effects of chemotherapy and radiotherapy causing severe oral pain and ulceration, which may complicate the management of cancer. The Mucositis Prevention Guideline Development Group has developed an international guideline for the prevention of mucositis in children receiving treatment for cancer or undergoing haematopoietic stem cell transplantation. Evidence-based preventative strategies include cryotherapy, low-level light therapy and keratinocyte growth factor. However, these strategies are often not available in resource-poor settings. There is some evidence that honey may be a suitable treatment for OM in adult patients. We performed a literature search of 11 databases to find papers exploring the use of honey to treat chemotherapy-associated mucositis in paediatric oncology patients. We found four papers, which provide Grade C evidence that honey is effective as a preventative and therapeutic measure for OM in paediatric oncology patients.

Photodynamic therapy for treatment of oral mucositis: Pilot study with pediatric patients undergoing chemotherapy.

Oral mucositis has become a major dose-limiting toxicity of antineoplastic treatment. The aim of this study was to evaluate the effect of photodynamic therapy (PDT) and low level laser therapy (LLLT) on the treatment of chemotherapy-induced mucositis in pediatric patients. An open, controlled, and blind, randomized clinical trial was conducted with 29 patients, from 10 months to 18 years old, who were divided into two groups. Group A was submitted to photodynamic therapy (0.01% Methylene Blue and red laser, λ660 nm) with 3J energy per point; and Group B submitted to low level laser therapy (λ660 nm) with 1J energy per point. The results were evaluated by using the WHO and ChIMES mucositis scales. The Chi-square, Exact Fisher, Student's-t and Mann-Whitney tests, and the mixed linear regression model were used for comparison between the groups, with the maximum error admitted of 5%. There was no difference between the groups as regards the number of sessions necessary for clinical cure of the oral lesions (p = 0.954) or reduction in pain reported by the patients (p = 0.258; p = 0.486). Within each group, however, there was significant reduction in pain (p = 0.032; p = 0.003). The number needed to treat (NNT) was 4.75. PDT or LLLT could be used for treatment of oral mucositis in children/young patients. Each were well tolerated and presented satisfactory results in reducing pain associated with the lesion.

Differential Effectiveness of Clinically-Relevant Analgesics in a Rat Model of Chemotherapy-Induced Mucositis.

Chemotherapy-induced intestinal mucositis is characterized by pain and a pro-inflammatory tissue response. Rat models are frequently used in mucositis disease investigations yet little is known about the presence of pain in these animals, the ability of analgesics to ameliorate the condition, or the effect that analgesic administration may have on study outcomes. This study investigated different classes of analgesics with the aim of determining their analgesic effects and impact on research outcomes of interest in a rat model of mucositis. Female DA rats were allocated to 8 groups to include saline and chemotherapy controls (n = 8). Analgesics included opioid derivatives (buprenorphine; 0.05mg/kg and tramadol 12.5mg/kg) and NSAID (carprofen; 15mg/kg) in combination with either saline or 5-Fluorouracil (5-FU; 150mg/kg). Research outcome measures included daily clinical parameters, pain score and gut histology. Myeloperoxidase assay was performed to determine gut inflammation. At the dosages employed, all agents had an analgesic effect based on behavioural pain scores. Jejunal myeloperoxidase activity was significantly reduced by buprenorphine and tramadol in comparison to 5-FU control animals (53%, p = 0.0004 and 58%, p = 0.0001). Carprofen had no ameliorating effect on myeloperoxidase levels. None of the agents reduced the histological damage caused by 5-FU administration although tramadol tended to increase villus length even when administered to healthy animals. These data provide evidence that carprofen offers potential as an analgesic in this animal model due to its pain-relieving efficacy and minimal effect on measured parameters. This study also supports further investigation into the mechanism and utility of opioid agents in the treatment of chemotherapy-induced mucositis.

PREVENTION AND TREATMENT OF MUCOSITIS AT AN ONCOLOGY OUTPATIENT CLINIC: A COLLECTIVE CONSTRUCTION

The aim was to develop a nursing care protocol for the prevention and treatment of chemotherapy-induced mucositis at an outpatient clinic of a High Complexity Center in Oncology. A qualitative convergent-care research was undertaken. The construction of the protocol was driven by the criteria of Evidence-Based Practice. Data were collected from January to June 2013 in two steps. Firstly, we collected data on medical charts of customers to obtain sociodemographic and therapeutic data and nursing interventions performed for prevention, detection and treatment of mucositis. After this first step, workshops were held with the nurses to validate the available material and human resources, besides the feasible care to compose the protocol. Care was related to oral hygiene, mouth rinse, cryotherapy, laser therapy and interventions related to the nutritional scope. The implementation of this care protocol has standardized the care strategies.

Activation of p38-MAPK by CXCL4/CXCR3 axis contributes to p53-dependent intestinal apoptosis initiated by 5-fluorouracil

Chemotherapy-induced mucositis (CIM) is a major does limiting side-effect of chemoagents such as 5-fluorouracil (5-FU). Molecules involved in this disease process are still not fully understood. We proposed that the homeostatically regulated genes during CIM may participate in the disease. A cluster of such genes were previously identified by expression gene-array from the mouse jejunum in 5-FU-induced mucositis model. Here, we report that CXCL4 is such a homeostatically regulated gene and serves as a new target for the antibody treatment of CIM. CXCL4 and its receptor CXCR3 were confirmed at both the gene and protein levels to be homeostatically regulated during 5-FU-induced mucositis. Using of CXCL4 neutralizing monoclonal antibody (CXCL4mab) decreased the incidence, severity, and duration of the chemotherapy-induced diarrhea, the major symptom of CIM, in a 5-FU mouse CIM model. Mechanistically, CXCL4mab reduced the apoptosis of the crypt epithelia by suppression of the 5-FU-induced expression of p53 and Bax through its receptor CXCR3. The downstream signaling pathway of CXCL4 in activation of the epithelial apoptosis was identified in an intestinal epithelial cell line (IEC-6). CXCL4 activated the phosphorylation of p38 MAPK, which mediated the stimulated expression of p53 and Bax, and resulted in the ultimate activation of Caspase-8, -9, and -3. Taken together, activation of CXCL4 expression by 5-FU in mice participates in 5-FU-induced intestinal mucositis through upregulation of p53 via activation of p38-MAPK, and CXCL4mab is potentially beneficial in preventing CIM in the intestinal tract.

Effect of SAMITAL ® in the Treatment of Chemotherapy-Induced Mucositis in Adult Oncohematological Patients

We sought to evaluate the efficacy and safety of SAMITAL(®) (Indena SpA, Milan, Italy), a highly standardized botanical formulation, in reducing mucositis in patients undergoing treatment for hematological malignancies. In this observational, uncontrolled study, a total of 25 consecutively enrolled patients (19 males, aged 18-74 years) with chemotherapy-induced mucositis were compassionately treated orally with SAMITAL (three to four times per day) for 4-22 days per cycle. Patients demonstrated clinically relevant reductions in WHO mucositis grade with a reduction in pain, mucosal erosions, bleeding, dysphagia/feeding impairment and improvements in quality of life. SAMITAL was well tolerated and no local or systemic pharmacological, allergic, toxic or synergistic/antagonistic side effects were reported. Of note, SAMITAL also showed efficacy when administered prophylactically. These results add weight to previous experiences with SAMITAL. However, randomized, placebo-controlled clinical trials will need to confirm the suitability of SAMITAL for use in the treatment of mucositis.

Glucagon-like peptide-1 as a treatment for chemotherapy-induced mucositis

BackgroundGlucagon-like peptide-2 (GLP-2) has been suggested for the treatment of mucositis, but the peptide has also been shown to accentuate colonic dysplasia in carcinogen-treated mice. Recently, an effect on intestinal...

BNP infusion during reperfusion increases cardiac triglyceride accumulation and decreases cardiac contractility after myocardial ischemia in pigs

Introduction: Chemotherapy induced mucositis (CIM) is a frequent complication to anticancer treatments. Glucagon-like peptide-2 (GLP-2) has been suggested for treatment of CIM, unfortunately the peptide is also shown to accentuate colonic dysplasia in carcinogen treated mice. Glucagon-like peptide 1(GLP-1) is secreted simultaneously with GLP-2 from the L-cell. GLP-1 is responsible for maintaining glucose homeostasis. Recently, an intestinal growth effect was discovered for GLP-1. Aim: The aim of this experiment was to elucidate if GLP-1 had a potential role in treating CIM. Methods: Mice were injected with 5-Fluorouracil (5-FU) or saline to induce mucositis and treated with a GLP-2 analogue, a GLP-1 analogue or vehicle. Mice were sacrificed 48 h after 5-FU injections. Endpoints were intestinal weight, villus height and histological scoring of mucositis severity. Rats were injected with 5-FU or saline and after 48 h blood was analysed for concentrations of GLP-1 and GLP-2. Results: Both peptides could significantly prevent the loss of mucosal mass and villus height and significantly decrease mucositis severity score in duodenum and jejunum. The effect was equivalent. GLP-1 and GLP-2 levels in blood were more than ten fold and seven fold increased respectively. Discussion: Both endogenous GLP-1 and GLP-2 were increased after intestinal injury, indicating an importance for the peptides for protection of the intestine. We found an equal effect of GLP-1 and GLP-2 in the treatment of CIM which opens up the possibility that mucositis as well as other acute intestinal disorders can benefit from treatment with GLP-1 analogues.

Glucagon-like Peptide-2 Does Not Modify the Growth or Survival of Murine or Human Intestinal Tumor Cells

Glucagon-like peptide-2 (GLP-2) secreted from enteroendocrine cells exerts proabsorptive, regenerative, and cytoprotective actions in the normal and injured gut epithelium. Hence, sustained GLP-2 receptor (GLP-2R) activation represents a strategy under investigation for the prevention and treatment of chemotherapy-induced mucositis. Nevertheless, the consequences of increased GLP-2R signaling for the growth and survival of intestinal tumor cells remain poorly understood. We studied the proliferative and cytoprotective actions of GLP-2 in human colon cancer cells stably transfected with the GLP-2R and in nude mice harboring GLP-2R(+) human colon cancer cells. The importance of the GLP-2R for tumor growth was also examined in Apc(Min/+) mice chronically treated with exogenous GLP-2 and in Apc(Min/+):Glp2r(-/-) mice. GLP-2 increased cyclic AMP accumulation and produced cell-specific activation of growth and survival pathways in DLD-1, SW480, and HT29 cells. However, GLP-2 did not stimulate cell growth or attenuate cycloheximide-, LY294002-, indomethacin-, or chemotherapy-induced cytotoxicity in vitro. Moreover, chronic GLP-2 administration had no effect on the growth of human colon cancer cell xenografts in nude mice in vivo. Daily GLP-2 treatment for 7 weeks increased growth of normal gut mucosa but did not increase the number or size of polyps in Apc(Min/+) mice, and genetic disruption of the Glp2r gene in Apc(Min/+) mice did not modify polyp size or number. Taken together, although GLP-2R activation engages signaling pathways promoting cell proliferation and cytoprotection in the normal gut epithelium, sustained direct or indirect modulation of GLP-2R signaling does not modify intestinal tumor cell growth or survival.

Vitamin E in the treatment of chemotherapy-induced mucositis

purpose: To determine the efficacy of vitamin E in the treatment of chemotherapy-induced mucositis in patients with malignancy. patients and methods: A randomized, double-blind, placebo-controlled study was performed to evaluate the efficacy of topical vitamin E in the treatment of oral mucositis in patients receiving chemotherapy for various types of malignancy. A total of 18 patients, 17 of whom had solid tumors and one with acute leukemia, were included in this study. Lesions were observed daily prior to and 5 days after topical application of either vitamin E or placebo oil. results: Six of nine patients receiving vitamin E had complete resolution of their oral lesions. In eight of nine patients who received placebo, complete resolution of their oral lesions was not observed. This difference is statistically significant ( p = 0.025 by Fisher's exact test). No toxicity was observed in this study. conclusion: These results suggest that vitamin E may be an effective therapy in patients with chemotherapy-induced mucositis.

Efficacy of oral sucralfate suspension in prevention and treatment of chemotherapy-induced mucositis

The efficacy of orally administered sucralfate suspension in preventing and treating chemotherapy-induced mucositis was evaluated in a double-blind trial. Forty-eight children and adolescents with newly diagnosed acute nonlymphocytic leukemia were randomized to receive suspensions of either sucralfate or placebo orally every 6 hours during the first 10 weeks of intensive remission-induction chemotherapy. Patients given sucralfate suspension were less likely than subjects receiving placebo to acquire colonization with potentially pathogenic microorganisms: 14 (58%) of 24 versus 22 (92%) of 24, respectively (p = 0.008). However, no effect on preexisting colonization was noted. Subjective reporting of discomfort, objective scoring of the severity of mucositis, and the maximal percent of body weight lost during therapy were similar; 58% of patients receiving sucralfate reported no oral pain compared with 25% receiving placebo (p = 0.06). Ten episodes of gastrointestinal bleeding, 25 documented infections, and 886 days with fever were also equally distributed between sucralfate and placebo groups. We conclude that sucralfate suspension is of limited, if any efficacy, in the prevention and treatment of chemotherapy-induced mucositis. Sucralfate administration can, however, reduce acquisition of alimentary colonization with potential pathogens, perhaps by interfering with adherence to mucosal membranes.