ORCID Profile
0000-0003-0876-0031
Current Organisation
University of Adelaide
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Publisher: Springer Science and Business Media LLC
Date: 10-09-2013
DOI: 10.1007/S00520-013-1942-0
Abstract: The purpose of this project was to evaluate research in basic oral care interventions to update evidence-based practice guidelines for preventing and treating oral mucositis (OM) in cancer patients undergoing radio- or chemotherapy. A systematic review of available literature was conducted by the Basic Oral Care Section of the Mucositis Study Group of MASCC/ISOO. Seven interventions--oral care protocols, dental care, normal saline, sodium bicarbonate, mixed medication mouthwash, chlorhexidine, and calcium phosphate--were evaluated using the Hadorn (J Clin Epidemiol 49:749-754, 1996) criteria to determine level of evidence, followed by a guideline determination of one of the following: recommendation, suggestion, or no guideline possible, using Somerfield's (Classic Pap Cur Comments 4:881-886, 2000) schema. Fifty-two published papers were examined by treatment population (radiotherapy, chemotherapy, and hematopoietic stem cell transplant) and by whether the intervention aimed to prevent or treat OM. The resulting practice suggestions included using oral care protocols for preventing OM across all treatment modalities and age groups and not using chlorhexidine mouthwash for preventing OM in adults with head and neck cancer undergoing radiotherapy. Considering inadequate and/or conflicting evidence, no guidelines for prevention or treatment of OM were possible for the interventions of dental care, normal saline, sodium bicarbonate, mixed medication mouthwash, chlorhexidine in patients receiving chemotherapy or hematopoietic stem cell transplant, or calcium phosphate. The evidence for basic oral care interventions supports the use of oral care protocols in patient populations receiving radiation and/or chemotherapy and does not support chlorhexidine for prevention of mucositis in head and neck cancer patients receiving radiotherapy. Additional well-designed research is needed for other interventions to improve the amount and quality of evidence guiding future clinical care.
Publisher: Springer Science and Business Media LLC
Date: 24-07-2014
DOI: 10.1007/S00280-014-2519-4
Abstract: Diarrhoea caused by treatment with receptor tyrosine kinase inhibitors (TKI) targeting Epidermal Growth Factor Receptors (EGFR) is an important clinical toxicity in oncology that remains poorly understood. This study aimed to identify histological and molecular changes within the intestine following lapatinib to elucidate mechanisms of diarrhoea related to treatment with this dual EGFR TKI. Male albino Wistar rats were orally gavaged lapatinib at 100, 240 or 500 mg/kg daily for 4 weeks and assessed for indicators of gastrointestinal injury at the end of each week. Lapatinib in combination with weekly paclitaxel (9 mg/kg i.p.) was also assessed for cumulative injury. At each time point, blood was collected for biochemical analysis. Sections or jejunum and colon were also collected and underwent immunohistochemistry and RT-PCR to detect markers of EGFR pathway signalling, and morphometric analysis to assess changes in mucosal architecture. Lapatinib (with or without paclitaxel co-treatment) caused dose-dependent changes in crypt length, mitotic rate and goblet cell morphology. Jejunal crypt expression of EGFR and ErbB2 were decreased, whilst no changes in Erk1/2 were observed. Markers of apoptosis (caspase-3) and proliferation (Ki-67) were only significantly altered in rats treated with both lapatinib and paclitaxel. In our novel rat model of lapatinib-induced diarrhoea we have shown that changes in small intestinal morphometry and expression of EGFR are associated with diarrhoea. Further research is required to test intervention agents for the prevention of diarrhoea.
Publisher: Wiley
Date: 20-04-2014
DOI: 10.1002/AIC.14469
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2013
Publisher: Informa Healthcare
Date: 09-2008
DOI: 10.1517/14728214.13.3.511
Abstract: Chemotherapy-induced mucositis is an increasingly recognized problem in cancer management, preventing full doses of treatment being given, compromising cure rates and reducing quality of life. Symptoms include mouth pain and ulceration, esophagitis, abdominal pain, bloating, and diarrhea. It is associated with increased infections and occasional mortality, and its palliation is very expensive. The pathobiology of mucositis is complex, and agents that target mechanisms to prevent mucositis or accelerate healing are in high demand. To review existing and potential treatments for chemotherapy-induced mucositis in the context of current knowledge of pathobiology. We searched for mucositis of any region of the gastrointestinal tract using Medline, the Pharmaprojects database and listed patents. There are many agents in varying stages of development for chemotherapy-induced mucositis. The field is complicated by the question of whether treatments should be developed as drugs or as medical foods, and whether the burden of proof of efficacy and safety should be different.
Publisher: Springer Science and Business Media LLC
Date: 22-09-2012
DOI: 10.1007/S00520-012-1605-6
Abstract: The aim of this study was to review the available literature and define clinical practice guidelines for the use of laser and other light therapies for the prevention and treatment of oral mucositis. A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology. The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, and no guideline possible. A new recommendation was made for low-level laser (wavelength at 650 nm, power of 40 mW, and each square centimeter treated with the required time to a tissue energy dose of 2 J/cm(2) (2 s oint)) for the prevention of oral mucositis in adult patients receiving hematopoietic stem cell transplantation conditioned with high-dose chemotherapy, with or without total body irradiation. A new suggestion was made for low-level laser (wavelength around 632.8 nm) for the prevention of oral mucositis in patients undergoing radiotherapy, without concomitant chemotherapy, for head and neck cancer. No guideline was possible in other populations and for other light sources due to insufficient evidence. The increasing evidence in favor of low-level laser therapy allowed for the development of two new guidelines supporting this modality in the populations listed above. Evidence for other populations was also generally encouraging over a range of wavelengths and intensities. However, additional well-designed research is needed to evaluate the efficacy of laser and other light therapies in various cancer treatment settings.
Publisher: Springer Science and Business Media LLC
Date: 24-05-2013
Publisher: Wiley
Date: 28-06-2016
DOI: 10.1111/AJCO.12226
Abstract: Complementary therapy use by patients with cancer is highly prevalent, although little is known about the optimal model of integration with conventional care. This study explored patient preferences regarding integration in an Australian context. Cancer patients participated in focus groups conducted by an experienced facilitator. Transcripts of discussions were subjected to thematic analysis. Fourteen female and four male patients took part in eight focus groups. Eleven had received conventional cancer treatment for early-stage disease, and seven for advanced stage. Participants had sound understanding of the distinction between complementary and alternative medicines. There were differing views on whether complementary therapy and conventional cancer services should be colocated. Some participants described colocation as discordant with their reasons for using complementary therapy. Participants valued guidance from oncology health professionals regarding complementary therapy that was tailored to their in idual needs. In addition to medical oncologists, nursing staff and affiliated complementary therapists were considered to be appropriate sources for guidance. Additional themes identified in the analysis were also informative: patients achieve autonomy and self-expression through complementary therapies the knowledge and attitudes of health professionals and limited consultation time are barriers to integration self-funding of complementary therapies is acceptable to participants. The study findings suggest that while patients have erse views regarding the optimal integration model, there is no strong preference for geographic colocation of complementary therapy with conventional cancer care. Patients valued personalized information and guidance regarding complementary therapy from health professionals involved in their cancer care.
Publisher: MDPI AG
Date: 30-09-2013
DOI: 10.3390/NU5103948
Publisher: Springer Science and Business Media LLC
Date: 08-07-2019
DOI: 10.1007/S00520-019-04893-Z
Abstract: Mucositis research and treatment are a rapidly evolving field providing constant new avenues of research and potential therapies. The MASCC/ISOO Mucositis Study Group regularly assesses available literature relating to pathogenesis, mechanisms, and novel therapeutic approaches and distils this to summary perspectives and recommendations. Reviewers assessed 164 articles published between January 2011 and June 2016 to identify progress made since the last review and highlight new targets for further investigation. Findings were organized into sections including established and emerging mediators of toxicity, potential insights from technological advances in mucositis research, and perspective. Research momentum is accelerating for mucositis pathogenesis, and with this has come utilization of new models and interventions that target specific mechanisms of injury. Technological advances have the potential to revolutionize the field of mucositis research, although focused effort is needed to move rationally targeted interventions to the clinical setting.
Publisher: Springer Science and Business Media LLC
Date: 21-09-2012
DOI: 10.1007/S00520-012-1562-0
Abstract: This systematic review analyzed the strength of the literature and defined clinical practice guidelines for the use of oral cryotherapy for the prevention and/or treatment of oral mucositis caused by cancer therapy. A systematic review on relevant oral cryotherapy studies indexed prior to 31 December 2010 was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO) using OVID/MEDLINE, with publications selected for review based on defined inclusion and exclusion criteria. Findings from the reviewed studies were integrated into guidelines based on the overall level of evidence for each intervention. Guidelines were classified into three types: recommendation, suggestion, or no guideline possible. Twenty-two clinical studies and two meta-analyses were analyzed. Results were compared with the MASCC/ISOO guidelines published in 2007. The recommendation for the use of oral cryotherapy to prevent oral mucositis in patients receiving bolus fluorouracil (5-FU) was maintained, in agreement with the 2007 guidelines. A suggestion for use of oral cryotherapy to prevent oral mucositis in patients receiving high-dose melphalan as conditioning regimen with or without total body irradiation for HCST was revised from the 2007 guidelines. No guideline was possible for any other intervention, due to insufficient evidence. The evidence continues to support the use of oral cryotherapy for prevention of oral mucositis in patients receiving bolus 5-FU chemotherapy or high-dose melphalan. This intervention is consistent with the MASCC/ISOO guidelines published in 2007. The literature is limited by the fact that utilization of a double-blind study design is not feasible. Future studies that compare efficacy of oral cryotherapy with other mucositis agents in patients receiving chemotherapy with relatively short plasma half-lives would be useful.
Publisher: Springer Science and Business Media LLC
Date: 31-07-2013
DOI: 10.1007/S00520-013-1884-6
Abstract: The aim of this systematic review was to analyze the available literature and define clinical practice guidelines for the use of the following agents for the prevention and treatment of oral mucositis (OM): allopurinol, midline mucosa-sparing radiation blocks, payayor, pentoxifylline, timing of radiation therapy (RT) (morning versus late afternoon), pilocarpine, bethanechol, chewing gum, propantheline, and tetrachlorodecaoxide. A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, no guideline possible. A total of 32 papers across 10 interventions were examined. New suggestions were developed against the use of systemic pilocarpine administered orally for prevention of OM during RT in head and neck cancer patients and in patients receiving high-dose chemotherapy, with or without total body irradiation, prior to hematopoietic stem cell transplantation. A suggestion was also made against the use of systemic pentoxifylline administered orally for the prevention of OM in patients undergoing bone marrow transplantation. No guideline was possible for any other agent reviewed due to inadequate and/or conflicting evidence. None of the agents reviewed was determined to be effective for the prevention or treatment of OM. Two agents, pilocarpine and pentoxifylline, were determined to be ineffective, in the populations listed above. Additional well-designed research is needed on other interventions.
Publisher: Wiley
Date: 12-2009
DOI: 10.1002/RRA.1226
Publisher: Springer Science and Business Media LLC
Date: 16-10-2015
DOI: 10.1007/S00520-014-2481-Z
Abstract: Severe chemotherapy-induced gastrointestinal toxicity (CIGT) is common and results in treatment delays, dose reductions, and potential premature treatment discontinuation. Currently, there is no diagnostic marker to predict CIGT. Proinflammatory cytokines, produced via toll-like receptor signaling, are key mediators of this toxicity. Hence, this pilot study investigated the association between immune genetic variability and severe CIGT risk. Genomic DNA from 34 patients (10 with severe CIGT) who had received 5-fluoruracil-based chemotherapy regimens was analyzed for variants of IL-1B, IL-2, IL-6, IL-6R, IL-10, TNF-a, TGF-b, TLR2, TLR4, MD2, MYD88, BDNF, CRP, ICE, and OPRM1. Multivariate logistic regression created a prediction model of severe CIGT risk. There were no significant differences between patients with and without severe CIGT with regards to age, sex, type of cancer, or chemotherapy treatment regimens. The prediction model of severe CIGT risk included TLR2 and TNF-a genetic variability and cancer type (colorectal and gastric). This prediction model was both specific and sensitive, with a receiver operator characteristic area under the curve of 87.3 %. This is the first report of immune genetic variability, together with cancer type, being predictive of severe CIGT risk. These outcomes are being validated in a larger patient population.
Publisher: Springer Science and Business Media LLC
Date: 06-07-2013
DOI: 10.1007/S00520-013-1871-Y
Abstract: The aim of this project was to develop clinical practice guidelines on the use of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the prevention and management of oral mucositis (OM) in cancer patients. A systematic review of the available literature was conducted. The body of evidence for the use of each agent, in each setting, was assigned a level of evidence. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, or no guideline possible. A recommendation was developed in favor of patient-controlled analgesia with morphine in hematopoietic stem cell transplant (HSCT) patients. Suggestions were developed in favor of transdermal fentanyl in standard dose chemotherapy and HSCT patients and morphine mouth rinse and doxepin rinse in head and neck radiation therapy (H&N RT) patients. Recommendations were developed against the use of topical antimicrobial agents for the prevention of mucositis. These included recommendations against the use of iseganan for mucositis prevention in HSCT and H&N RT and against the use of antimicrobial lozenges (polymyxin-tobramycin- hotericin B lozenges aste and bacitracin-clotrimazole-gentamicin lozenges) for mucositis prevention in H&N RT. Recommendations were developed against the use of the mucosal coating agent sucralfate for the prevention or treatment of chemotherapy-induced or radiation-induced OM. No guidelines were possible for any other agent due to insufficient and/or conflicting evidence. Additional well-designed research is needed on prevention and management approaches for OM.
Publisher: Springer Science and Business Media LLC
Date: 23-10-2019
DOI: 10.1007/S00520-018-4511-8
Abstract: Gastrointestinal mucositis (GIM) is one of the most debilitating side effects of the chemotherapy agent, irinotecan hydrochloride (CPT-11). The toll-like receptor (TLR) pathway is a key mediator implicated in the pathophysiology underlying GIM. The tricyclic antidepressant amitriptyline has been shown to inhibit TLR2 and TLR4 activity in in vitro models. The aim of this study was therefore to investigate the effect of amitriptyline on the development of GIM following CPT-11. Male albino Wistar rats were treated with either CPT-11 (125 mg/kg, i.p., n = 18), amitriptyline (20 mg/kg, n = 18), both agents (n = 18), or vehicle control (n = 18) and killed at 6, 48, or 96 h. Differences between groups in measurements of gastrointestinal toxicity (diarrhea and weight loss), mucosal injury (apoptosis and histopathology score), colonic expression of TLRs, and pro-inflammatory cytokines were determined. CPT-11-induced diarrhea and colonic apoptosis were inhibited by amitriptyline at 6 h. However, rats were not protected from weight loss or mucosal injury over the time course of CPT-11-induced GIM. Interleukin-1 beta transcript expression was significantly decreased with amitriptyline treatment at 6 h, although protein expression did not differ between groups. There was no change in TLR4 or TLR2 expression in any group. Prophylactic amitriptyline was able to inhibit early intestinal damage in this rat model of CPT-11-induced GIM, but exacerbated late-onset injury. These findings do not support use of amitriptyline as an approach for mitigation of GIM in this setting.
Publisher: Springer Science and Business Media LLC
Date: 03-10-2012
DOI: 10.1007/S00520-012-1613-6
Abstract: The aim of this study was to review the available literature from 1966 until December 31, 2010 and define clinical practice guidelines for the use of amifostine for the prevention and treatment of oral mucositis in cancer patients. A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology. The body of evidence for the use of amifostine, in each cancer treatment setting was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, or no guideline possible. Thirty papers were reviewed for evidence on amifostine as an intervention for oral mucositis. No guideline was possible for amifostine in any cancer treatment setting due to inadequate and conflicting evidence. Review of the amifostine studies for the prevention and treatment of oral mucositis has found insufficient evidence to support its use in any cancer treatment setting for this purpose. Additional well-designed research is needed to clarify the role of amifostine as an intervention for oral mucositis.
Publisher: IEEE
Date: 06-2019
Publisher: SAGE Publications
Date: 03-2012
Publisher: Wiley
Date: 17-12-2014
DOI: 10.1002/CNCR.29174
Publisher: Springer Science and Business Media LLC
Date: 23-05-2023
DOI: 10.1038/S41419-023-05850-9
Abstract: Cytotoxicity (i.e. cell death) is the core mechanism by which chemotherapy induces its anti-cancer effects. Unfortunately, this same mechanism underpins the collateral damage it causes to healthy tissues. The gastrointestinal tract is highly susceptible to chemotherapy’s cytotoxicity, resulting in ulcerative lesions (termed gastrointestinal mucositis, GI-M) that impair the functional capacity of the gut leading to diarrhea, anorexia, malnutrition and weight loss, which negatively impact physical sychological wellbeing and treatment adherence. Preventing these side effects has proven challenging given the overlapping mechanisms that dictate chemotherapy efficacy and toxicity. Here, we report on a novel dietary intervention that, due to its localized gastrointestinal effects, is able to protect the intestinal mucosal from unwanted toxicity without impairing the anti-tumor effects of chemotherapy. The test diet (containing extensively hydrolyzed whey protein and medium chain triglycerides (MCTs)), was investigated in both tumor-naïve and tumor-bearing models to evaluate its effect on GI-M and chemo-efficacy, respectively. In both models, methotrexate was used as the representative chemotherapeutic agent and the diet was provided ad libitum for 14 days prior to treatment. GI-M was measured using the validated biomarker plasma citrulline, and chemo-efficacy defined by tumor burden (cm 3 /g body weight). The test diet significantly attenuated GI-M ( P = 0.03), with associated reductions in diarrhea ( P 0.0001), weight loss ( P 0.05), daily activity ( P 0.02) and maintenance of body composition ( P 0.02). Moreover, the test diet showed significant impact on gut microbiota by increasing ersity and resilience, whilst also altering microbial composition and function (indicated by cecal short and brained chain fatty acids). The test diet did not impair the efficacy of methotrexate against mammary adenocarcinoma (tumor) cells. In line with the first model, the test diet minimized intestinal injury ( P = 0.001) and diarrhea ( P 0.0001). These data support translational initiatives to determine the clinical feasibility, utility and efficacy of this diet to improve chemotherapy treatment outcomes.
Publisher: Hindawi Limited
Date: 28-06-2022
DOI: 10.1155/2022/4165808
Abstract: Lapatinib, an orally administered small-molecule tyrosine kinase inhibitor (SM-TKI), is an effective treatment for ErbB2-positive breast cancer. However, its efficacy as one of the targeted cancer therapies has been h ered by several adverse effects, especially gastrointestinal toxicity, commonly manifested as diarrhoea. Although it can be generally tolerated, diarrhoea is reported as the most common and most impactful on a patient’s quality of life and associated with treatment interruption. Severe diarrhoea can result in malabsorption, leading to dehydration, fatigue, and even death. ErbB1 is an epidermal growth factor profoundly expressed in normal gut epithelium while lapatinib is a dual ErbB1/ErbB2 tyrosine kinase inhibitor. Thus, ErbB1 inhibition by lapatinib may affect gut homeostasis leading to diarrhoea. Nevertheless, the underlying mechanisms remain unclear. This review article provides evidence of the possible mechanisms of lapatinib-induced diarrhoea that may be related to/or modulated by ErbB1. Insight regarding the involvement of ErbB1 in the pathophysiological changes such as inflammation and intestinal permeability as the underlying cause of diarrhoea is covered in this article.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2013
Publisher: Springer Science and Business Media LLC
Date: 05-12-2014
Publisher: Springer Science and Business Media LLC
Date: 26-06-2020
Publisher: IEEE
Date: 10-2019
Publisher: Bentham Science Publishers Ltd.
Date: 06-2008
DOI: 10.2174/157489208784638802
Abstract: Current standard treatments for cancer are associated with major dose-limiting toxic effects on healthy tissue. The mucosal layers of the body are particularly sensitive to regimen-induced damage, with patients suffering many unpleasant and potentially life-threatening side-effects. In recent years, there has been an increase in the understanding of the pathobiology of regimen-related mucosal injury which has lead to a number of exciting inventions for its prevention and treatment being recently patented. Agents such as growth factors, cytokines, receptor agonists/antagonists and anti-inflammatory agents are among those in development in this emerging field. The complexity of mucosal injury poses a challenge for researchers, however rational targeting of intervention strategies to critical mechanisms will lead to further progress.
Publisher: Springer Science and Business Media LLC
Date: 06-05-2015
DOI: 10.1007/S11605-015-2829-9
Abstract: The poor prognosis and rising incidence of esophageal adenocarcinoma highlight the need for improved detection methods. The potential for circulating microRNAs (miRNAs) as biomarkers in other cancers has been shown, but circulating miRNAs have not been well characterized in esophageal adenocarcinoma. We investigated whether circulating exosomal miRNAs have potential to discriminate in iduals with esophageal adenocarcinoma from healthy controls and non-dysplastic Barrett's esophagus. Seven hundred fifty-eight miRNAs were profiled in serum circulating exosomes from a cohort of 19 healthy controls, 10 in iduals with Barrett's esophagus, and 18 in iduals with locally advanced esophageal adenocarcinoma. MiRNA expression was assessed using all possible permutations of miRNA ratios per in idual. Four hundred eight miRNA ratios were differentially expressed in in iduals with cancer compared to controls and Barrett's esophagus (Mann-Whitney U test, P < 0.05). The 179/408 ratios discriminated esophageal adenocarcinoma from healthy controls and Barrett's esophagus (linear regression, P 0.7, P < 0.05). A multi-biomarker panel (RNU6-1/miR-16-5p, miR-25-3p/miR-320a, let-7e-5p/miR-15b-5p, miR-30a-5p/miR-324-5p, miR-17-5p/miR-194-5p) demonstrated enhanced specificity and sensitivity (area under ROC = 0.99, 95% CI 0.96-1.0) over single miRNA ratios to distinguish esophageal adenocarcinoma from controls and Barrett's esophagus. This study highlights the potential for serum exosomal miRNAs as biomarkers for the detection of esophageal adenocarcinoma.
Publisher: Springer Science and Business Media LLC
Date: 24-01-2022
Publisher: Springer Science and Business Media LLC
Date: 09-09-2013
DOI: 10.1007/S00520-012-1592-7
Abstract: Members of the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) recently completed the process of updating the MASCC/ISOO Clinical Practice Guidelines for the prevention and treatment of mucositis. These guidelines, originally published in 2004, and last updated in 2007, provide clinicians with objective, evidence-based recommendations for the management of mucositis secondary to cancer therapy. This brief paper describes the methodology used to conduct the most recent systematic review in 2011, and develop new guidelines, providing the basis for the update. The overriding aims of the process were to assess evidence of effectiveness of interventions for the prevention and treatment of mucositis and to produce clinical practice guidelines for the management of mucositis using best available evidence.
Publisher: Springer Science and Business Media LLC
Date: 13-10-2012
DOI: 10.1007/S00520-012-1593-6
Abstract: The Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) recently conducted a systematic review to update the MASCC/ISOO clinical practice guidelines for oral and gastrointestinal mucositis. Here, we discuss the details of some considerations underlying the process used.
Publisher: Springer Science and Business Media LLC
Date: 18-09-2012
DOI: 10.1007/S00520-012-1594-5
Abstract: The aim of this project was to review the literature and define clinical practice guidelines for the use of cytokines and growth factor agents for the prevention or treatment of oral mucositis induced by cancer chemotherapy or radiotherapy. A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: Recommendation, Suggestion, No guideline possible. Sixty-four clinical studies across 11 interventions were evaluated. A recommendation was made for the use of recombinant human KGF-1 (palifermin) at a dose of 60 μg/kg per day for 3 days prior to conditioning treatment and for 3 days post-transplant for prevention of oral mucositis in patients receiving high-dose chemotherapy and total body irradiation followed by autologous stem cell transplantation for hematological malignancies. A suggestion was made against using granulocyte macrophage colony-stimulating factor mouthwash for the prevention of oral mucositis in the setting of high-dose chemotherapy followed by autologous or allogeneic stem cell transplantation. No guideline was possible for any other cytokine or growth factor agents due to inconclusive evidence. Of the cytokine and growth factor agents studied for oral mucositis, the evidence only supports use of palifermin in the specific population listed above. Additional well-designed research is needed on other cytokine and growth factor interventions and in other cancer treatment settings.
Publisher: Springer Science and Business Media LLC
Date: 14-06-2013
DOI: 10.1007/S00520-013-1869-5
Abstract: The aim of this study was to review the available literature and define clinical practice guidelines for the use of natural agents for the prevention and treatment of oral mucositis. A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology. The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, and no guideline possible. A total of 49 papers across 15 interventions were examined. A new suggestion was developed in favor of systemic zinc supplements administered orally in the prevention of oral mucositis in oral cancer patients receiving radiation therapy or chemoradiation (Level III evidence). A recommendation was made against the use of intravenous glutamine for the prevention of oral mucositis in patients receiving high-dose chemotherapy prior to hematopoietic stem cell transplant (Level II evidence). No guideline was possible for any other agent, due to inadequate and/or conflicting evidence. Of the various natural agents reviewed here, the available evidence supported a guideline only for two agents: a suggestion in favor of zinc and a recommendation against glutamine, in the treatment settings listed above. Well-designed studies of other natural agents are warranted.
Publisher: Informa UK Limited
Date: 16-08-2012
DOI: 10.4161/CBT.21783
Publisher: Springer Science and Business Media LLC
Date: 21-10-2016
DOI: 10.1007/S00280-016-3165-9
Abstract: A common side effect of irinotecan administration is gastrointestinal mucositis, often manifesting as severe diarrhoea. The damage to the structure and function of the gastrointestinal tract caused by this cytotoxic agent is debilitating and often leads to alterations in patients' regimens, hospitalisation or stoppage of treatment. The purpose of this review is to identify mechanisms of irinotecan-induced intestinal damage and a potential role for GLP-2 analogues for intervention. This is a review of current literature on irinotecan-induced mucositis and GLP-2 analogues mechanisms of action. Recent studies have found alterations that appear to be crucial in the development of severe intestinal mucositis, including early apoptosis, alterations in proliferation and cell survival pathways, as well as induction of inflammatory cascades. Several studies have indicated a possible role for glucagon-like peptide-2 analogues in treating this toxicity, due to its proven intestinotrophic, anti-apoptotic and anti-inflammatory effects in other models of gastrointestinal disease. This review provides evidence as to why and how this treatment may improve mucositis through the possible molecular crosstalk that may be occurring in models of severe intestinal mucositis.
Publisher: Springer Science and Business Media LLC
Date: 27-03-2015
DOI: 10.1007/S00520-015-2696-7
Abstract: Esophageal cancer has a high mortality rate, and its multimodality treatment is often associated with significant rates of severe toxicity. Effort is needed to uncover ways to maximize effectiveness of therapy through identification of predictive markers of response and toxicity. As such, the aim of this study was to identify genes predictive of chemoradiotherapy-induced gastrointestinal toxicity using an immune pathway-targeted approach. Adults with esophageal cancer treated with chemotherapy consisting of 5-fluorouracil and cisplatin and 45-50 Gy radiation were recruited to the study. Pre-therapy-collected whole blood was analyzed for relative expression of immune genes using real-time polymerase chain reaction (RT-PCR). Gene expression was compared between patients who experienced severe regimen-related gastrointestinal toxicity vs. those experiencing mild to moderate toxicity. Blood from 31 patients were analyzed by RT-PCR. Out of 84 immune genes investigated, TNF was significantly elevated (2.05-fold, p = 0.025) in the toxic group (n = 12) compared to the non-toxic group (n = 19). Nausea and vomiting was the most commonly documented severe toxicity. No associations between toxicity and response, age, sex, histology, or treatment were evident. This study supports evidence of TNF as a predictive biomarker in regimen-related gastrointestinal toxicity. Confirming these findings in a larger cohort is warranted.
Publisher: Springer Science and Business Media LLC
Date: 04-2006
DOI: 10.1007/S00520-006-0058-1
Abstract: Our understanding of the biological basis for mucosal barrier injury (mucositis) induced by cancer therapy with radiation or drugs continues to evolve. A patient's mucosal response to cancer therapy appears to be controlled by both global (i.e. gender, underlying systemic disease, race) and tissue specific (i.e. epithelial type, intrinsic endocrine system, local microbial environment, function) factors. Interactions of these elements, coupled with underlying genetic influences, most likely govern the risk, course and severity of regimen-related mucosal injury.
Publisher: Wiley
Date: 30-07-2020
DOI: 10.1002/JCP.29976
Publisher: SAGE Publications
Date: 11-06-2019
Abstract: Gastrointestinal toxicity arising from cancer treatment remains a key reason for treatment discontinuation, significantly compromising remission. There are drawbacks to the currently used in vitro and rodent models, and a lack of translatability from in vitro to in vivo work. A screening-amenable alternative in vivo model such as zebrafish would, therefore, find immediate application. This study utilized a transgenic reporter line of zebrafish, Tg(cyp2k18:egfp), that shows eGFP induction as an indicator of drug-induced pathology. Here, we investigate its utility as an alternative vertebrate model to bridge the gap between simple in vitro cellular studies and complex in vivo models for understanding gastrointestinal toxicity induced by chemotherapy and targeted therapy. Transgenic zebrafish larvae were administered afatinib or SN38, and assessed for viability and eGFP induction. Adult zebrafish were administered afatinib via oral gavage, and SN38 via intraperitoneal injection. Fish were killed after 24 h, and had gastrointestinal tracts removed and assessed for histopathological damage, goblet cell changes, and apoptosis. While treatment with either compound did not induce eGFP in the gastrointestinal tract of larvae, SN38 caused histopathological damage to adult intestines. The lack of eGFP induction may be due to poor solubility of the drugs. Chemotherapy agents with high solubility and permeability would be more amenable to these models. Further progress in this area would be greatly facilitated by the generation of robust and reproducible genetic models of zebrafish intestinal toxicity that mimic the known pathobiological pathways in rodents and humans, and can be readily induced in a short time-frame. Gastrointestinal toxicity secondary to cancer treatment remains a major reason for the termination of cancer drug candidates in the development pipeline as well as withdrawal or restrictions of marketed drugs. Current cancer treatment-induced gastrointestinal toxicity models available are limited to in vitro and rodent models that lack translatability and are prohibitively expensive and time consuming. An alternative model to study cancer treatment-induced gastrointestinal toxicity that allows rapid, miniaturized, multi-organ toxicity, screening-amenable testing is therefore warranted. The newly developed Tg( cyp2k18:egfp) zebrafish reporter line was found to induce eGFP in the gastrointestinal tract if toxicity was induced in this area. This paper explored utilizing this reporter line for cancer treatment-induced gastrointestinal toxicity, but found that it was not a useful reporter line in this setting. Further progress in this area would be greatly facilitated by the generation of robust and reproducible genetic models of zebrafish intestinal toxicity that mimic the known pathobiological pathways.
Publisher: Springer Science and Business Media LLC
Date: 08-07-2019
DOI: 10.1007/S00520-019-04892-0
Abstract: The aim of this study was to update the clinical practice guidelines for the use of agents for the prevention and/or treatment of gastrointestinal mucositis (GIM). A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: Recommendation, Suggestion, and No Guideline Possible. A total of 78 papers across 13 interventions were examined of which 25 were included in the final review. No new guidelines were possible for any agent due to inadequate and/or conflicting evidence. Existing guidelines for probiotics and hyperbaric oxygen were unchanged. Of the agents studied for the prevention and treatment of GIM, the evidence continues to support use of probiotics containing Lactobacillus spp. for prevention of chemoradiotherapy and radiotherapy-induced diarrhea in patients with pelvic malignancy, and hyperbaric oxygen therapy to treat radiation-induced proctitis. Additional well-designed research is encouraged to enable a decision regarding palifermin, glutamine, sodium butyrate, and dietary interventions, for the prevention or treatment of GIM.
Publisher: Wiley
Date: 27-08-2007
Publisher: Informa UK Limited
Date: 10-1999
No related grants have been discovered for Joanne Bowen.