MASCC/ISOO expert opinion on the management of oral problems in patients with advanced cancer.

PURPOSE: The Palliative Care Study Group in conjunction with the Oral Care Study Group of the Multinational Association for Supportive Care in Cancer (MASCC) formed a sub-group to develop evidence-based guidance on the management of common oral problems in patients with advanced cancer. METHODS: This guidance was developed in accordance with the MASCC Guidelines Policy. A search strategy for Medline was developed, and the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials were explored for relevant reviews and trials, respectively. Guidance was categorised by the level of evidence, and "category of guideline" (i.e., "recommendation", "suggestion" or "no guideline possible"). RESULTS: Twelve generic suggestions (level of evidence - 5), three problem-specific recommendations and 14 problem-specific suggestions were generated. The generic suggestions relate to oral hygiene measures, assessment of problems, principles of management, re-assessment of problems and the role of dental/oral medicine professionals. CONCLUSIONS: This guidance provides a framework for the management of common oral problems in patients with advanced cancer, although every patient requires individualised management.

Aerosol Pirfenidone Pharmacokinetics after Inhaled Delivery in Sheep: a Viable Approach to Treating Idiopathic Pulmonary Fibrosis.

PURPOSE: Inhaled delivery of pirfenidone to the lungs of patients with idiopathic pulmonary fibrosis holds promise to eliminate oral-observed side effects while enhancing efficacy. This study aimed to comprehensively describe the pulmonary pharmacokinetics of inhaled aerosol pirfenidone in healthy adult sheep. METHODS: Pirfenidone concentrations were evaluated in plasma, lung-derived lymph and epithelial lining fluid (ELF) with data subjected to non-compartmental pharmacokinetic analysis. RESULTS: Compartmental pharmacokinetic evaluation indicated that a 49 mg lung-deposited dose delivered an ELF Cmax of 62 ± 23 mg/L, and plasma Cmax of 3.1 ± 1.7 mg/L. Further analysis revealed that plasma pirfenidone reached Tmax faster and at higher concentrations than in lymph. These results suggested inhaled pirfenidone was cleared from the alveolar interstitium via blood faster than the drug could equilibrate between the lung interstitial fluid and lung lymphatics. However, the data also suggested that a 'reservoir' of pirfenidone feeds into lung lymph at later time points (after it has largely been cleared from plasma), prolonging lung lymphatic exposure. CONCLUSIONS: This study indicates inhaled pirfenidone efficiently deposits in ELF and is cleared from the lungs by initial absorption into plasma, followed by later equilibrium with lung interstitial and lymph fluid.

A cluster randomised feasibility trial of clinically assisted hydration in cancer patients in the last days of life.

BACKGROUND: The provision of clinically assisted hydration at the end-of-life is one of the most contentious issues in medicine. AIM: The aim of this feasibility study was to answer the question 'can a definitive (adequately powered) study be done?' DESIGN: The study was a cluster randomised trial, with sites randomised on a one-to-one basis to intervention 'A' (regular mouth care and usual other care) or intervention 'B' (clinically assisted hydration, mouth care and usual other care). Participants were assessed every 4 h, and data collected on clinical problems, therapeutic interventions and overall survival. SETTING/PARTICIPANTS: The study was conducted at 12 sites/'clusters' with specialist palliative care teams (4 cancer centres and 8 hospices), and participants were cancer patients in the last week of life who were unable to maintain sufficient oral fluid intake. RESULTS: The study achieved its pre-determined criteria for success. Two hundred patients were recruited to the study, and 199 participants completed the study, over a 1-year period. A total of 38.5% participants discontinued clinically assisted hydration due to adverse effects: none of these adverse events were rated as 'severe' or worse in intensity. The primary reasons for discontinuation were site problems ( n = 2), localised oedema ( n = 13), generalised oedema ( n = 5), respiratory secretions ( n = 6) and nausea and vomiting ( n = 1). CONCLUSION: The results of this feasibility study suggest that a definitive study can be done, but that minor changes are needed to the protocol to standardise the administration of clinically assisted hydration (which may reduce the incidence of certain adverse effects).

Disparities Between Clinician and Patient Perception of Breakthrough Pain Control.

CONTEXT: There are disparities in the level of symptom severity as perceived by patients and health professionals. There is limited information about patients' and clinicians' global assessment of breakthrough pain control, the need to change analgesics, and change in breakthrough pain over time. OBJECTIVES: To establish whether patients and clinicians independently agree on adequacy of breakthrough pain control, management strategy, and impression of change over time. METHODS: One hundred patients with breakthrough cancer pain were assessed and followed up one week later by a palliative medicine specialist. The patient and clinician independently answered the same questions about the adequacy of the patient's breakthrough pain control and breakthrough pain management. The results were compared with items on the Breakthrough Pain Assessment Tool (BAT). RESULTS: At initial consultation, 35% of patients rated their breakthrough cancer pain as inadequately controlled compared with 72% of clinicians. Breakthrough pain analgesics were changed in 68% of cases. At one-week follow-up consultation, 62% of patients considered their breakthrough cancer pain to be better, and in 57% of cases, the clinicians also categorized the pain this way. CONCLUSION: There are significant differences in global impressions of breakthrough pain between patients and pain clinicians that become less disparate as a therapeutic relationship evolves. Therapeutic decisions were based on clinical rather than patient perceptions.

Parasympathomimetic drugs for the treatment of salivary gland dysfunction due to radiotherapy.

BACKGROUND: This is an updated version of the original Cochrane review on parasympathomimetic drugs for the treatment of salivary gland dysfunction due to radiotherapy (published in Issue 3, 2007). Salivary gland dysfunction is a predictable side effect of radiotherapy to the head and neck region. Pilocarpine hydrochloride (a choline ester) is licensed in many countries for the treatment of radiation-induced salivary gland dysfunction. Other parasympathomimetics have also been used 'off licence' in the treatment of this condition. OBJECTIVES: To determine the efficacy and tolerability of parasympathomimetic drugs in the treatment of radiation-induced salivary gland dysfunction (specifically radiation-induced xerostomia). SEARCH METHODS: For this update, we ran searches of the Cochrane Oral Health Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 6), MEDLINE, EMBASE, and CINAHL in July 2015. We checked the reference lists of retrieved articles for additional studies, contacted experts in the field for unpublished and ongoing trials, and contacted relevant pharmaceutical companies for unpublished and ongoing trials. SELECTION CRITERIA: The selection criteria for the review were: 1) randomised controlled trials; 2) people suffering from radiation-induced salivary gland dysfunction; 3) people treated with parasympathomimetic drugs; and 4) assessable data available on primary outcome measure. DATA COLLECTION AND ANALYSIS: The two review authors independently collected data from the full-text version of relevant papers including: 1) citation details; 2) participants; 3) interventions; 4) assessments; 5) outcomes (that is efficacy, tolerability); and 6) quality issues.Due to a lack of appropriate data, we were unable to perform a meta-analysis. MAIN RESULTS: In the original review, three studies, including a total of 298 participants, fulfilled the inclusion criteria. All three studies involved the use of pilocarpine hydrochloride. We have included no additional studies in the update of the review; we have excluded eight additional studies.The data suggest that pilocarpine hydrochloride is more effective than placebo and at least as effective as artificial saliva. The response rate was 42% to 51%. The time to response was up to 12 weeks. The overall side effect rate was high, and side effects were the main reason for withdrawal (6% to 15% of participants taking 5 mg three times a day had to withdraw). The side effects were usually the result of generalised parasympathomimetic stimulation (for example sweating, headaches, urinary frequency, vasodilatation). Response rates were not dose dependent, but side effect rates were dose dependent. AUTHORS' CONCLUSIONS: There is limited evidence to support the use of pilocarpine hydrochloride in the treatment of radiation-induced xerostomia. Currently, there is little evidence to support the use of other parasympathomimetic drugs in the treatment of radiation-induced xerostomia. Available studies suggest that approximately half of patients will respond, but side effects can be problematic. The conclusions of the update are the same as the conclusions of the original review, since no new relevant studies have been published in the interim.

Accuracy of a Diagnostic Algorithm to Diagnose Breakthrough Cancer Pain as Compared With Clinical Assessment.

CONTEXT: Breakthrough cancer pain (BTCP) is a heterogeneous condition, and there are no internationally agreed standardized criteria to diagnose it. There are published algorithms to assist with diagnosis, but these differ in content. There are no comparative data to support use. OBJECTIVES: To compare the diagnostic ability of a simple algorithm against a comprehensive clinical assessment to diagnose BTCP and to assess if verbal rating descriptors can adequately discriminate controlled background pain. METHODS: Patients with cancer pain completed a three-step algorithm with a researcher to determine if they had controlled background pain and BTCP. This was followed by a detailed pain consultation with a clinical specialist who was blinded to the algorithm results and determined an independent pain diagnosis. The sensitivity, specificity, and positive and negative predictive values were calculated for the condition of BTCP. Further analysis determined which verbal pain severity descriptors corresponded with the condition of controlled background pain. RESULTS: The algorithm had a sensitivity of 0.54 and a specificity of 0.76 in the identification of BTCP. The positive predictive value was 0.7, and the negative predictive value was 0.62. The sensitivity of a background pain severity rating of mild or less to accurately categorize controlled background pain was 0.69 compared with 0.97 for severity of moderate or less; however, this was balanced by a higher specificity rating for mild or less, 0.78 compared with 0.2. CONCLUSION: The diagnostic breakthrough pain algorithm had a good positive predictive value but limited sensitivity using a cutoff score of "mild" to define controlled background pain. When the cutoff level was changed to moderate, the sensitivity increased, but specificity reduced. A comprehensive clinical assessment remains the preferred method to diagnose BTCP.

Development and validation of the breakthrough pain assessment tool (BAT) in cancer patients.

CONTEXT: The successful management of breakthrough pain depends on a combination of adequate assessment, appropriate (individualized) treatment, and adequate re-assessment. Currently, there is no fully validated clinical assessment tool for breakthrough pain in cancer patients. OBJECTIVES: The aim of this project was to develop and validate a breakthrough pain assessment tool (the BAT) for use in the clinical setting. METHODS: The content of the BAT was determined by reviewing the medical literature, conducting a Delphi process with experts in breakthrough pain and/or pain assessment and conducting semi-structured interviews with cancer patients with breakthrough pain. The tool was then subjected to a series of standard psychometric tests to assess its factor structure, validity (i.e., content validity, construct validity), reliability (i.e., internal consistency, test-retest reliability), and responsiveness to change. RESULTS: The BAT comprised two pages with 14 questions. Factor analysis confirmed the presence of two underlying factors. Psychometric testing confirmed that the tool is valid, reliable, and responsive to change. CONCLUSION: This study provides initial evidence for the validity and reliability of the breakthrough pain assessment tool which may be used to facilitate the management of patients with breakthrough cancer pain in the clinical setting.

Breakthrough cancer pain.

Breakthrough pain is a distinct pain state that is common in patients with cancer pain and which is associated with significant morbidity in this group of patients. The aim of this article is to highlight important journal articles relating to breakthrough pain that have been published within the last year, including a systematic review of the epidemiology of breakthrough pain, the largest-ever study of the clinical features of breakthrough pain, and a network meta-analysis of the treatment of breakthrough pain.

Opioids for the management of breakthrough pain in cancer patients.

BACKGROUND: This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (Issue 1, 2006). Breakthrough pain is a transient exacerbation of pain that occurs either spontaneously or in relation to a specific predictable or unpredictable trigger despite relative stable and adequately controlled background pain. Breakthrough pain usually related to background pain and is typically of rapid onset, severe in intensity and generally self limiting with a mean duration of 30 minutes. Breakthrough pain has traditionally been managed by the administration of supplemental oral analgesia (rescue medication) at a dose proportional to the total around-the-clock (ATC) opioid dose. OBJECTIVES: To determine the efficacy of opioid analgesics given by any route, used for the management of breakthrough pain in patients with cancer, and to identify and quantify, if data permitted, any adverse effects of this treatment. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and trial registries in January 2005 for the original review, and again on 6 February 2013 for this update. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of opioids used as rescue medication against active or placebo comparator in patients with cancer pain. Outcome measures sought were reduction in pain intensity measured by an appropriate scale, adverse effects, attrition, patient satisfaction and quality of life. We applied no language restrictions. DATA COLLECTION AND ANALYSIS: Two review authors independently selected and examined eligible studies. We retrieved full text if any uncertainty about eligibility remained. We screened non-English texts. We conducted quality assessment and data extraction using standardised data forms. We compared drug and placebo dose, titration, route and formulation and recorded details of all outcome measures (if available). MAIN RESULTS: The original review included four studies (393 participants), all concerned with the use of oral transmucosal fentanyl citrate (OTFC) in the management of breakthrough pain. Two studies examined the titration of OTFC, one study compared OTFC versus normal-release morphine and one study compared OTFC versus placebo.Fifteen studies (1699 participants) met the inclusion criteria for this update. All studies reported on the utility of seven different transmucosal fentanyl formulations, five of which were administered orally and two nasally. Eight studies compared the transmucosal fentanyl formulations versus placebo, four studies compared them with another opioid, one study was a comparison of different doses of the same formulation and two were randomised titration studies. Oral and nasal transmucosal fentanyl formulations were an effective treatment for breakthrough pain. When compared with placebo or oral morphine, participants gave lower pain intensity and higher pain relief scores for transmucosal fentanyl formulations at all time points. Global assessment scores also favoured transmucosal fentanyl preparations. One study compared intravenous with the transmucosal route and both were effective. AUTHORS' CONCLUSIONS: Oral and nasal transmucosal fentanyl is an effective treatment in the management of breakthrough pain. The RCT literature for the management of breakthrough pain is relatively small. Given the importance of this subject, more trials, including head-to-head comparisons of the available transmucosal fentanyl formulations are required.

WITHDRAWN: Opioids for the palliation of breathlessness in advanced disease and terminal illness.

BACKGROUND: Breathlessness is a common symptom in people with advanced disease. The most effective treatments are aimed at treating the underlying cause of the breathlessness but this may not be possible and symptomatic treatment is often necessary. Strategies for the symptomatic treatment of breathlessness have never been systematically evaluated. Opioids are commonly used to treat breathlessness: the mechanisms underlying their effectiveness are not completely clear and there have been few good-sized trials in this area. OBJECTIVES: To determine the effectiveness of opioid drugs given by any route in relieving the symptom of breathlessness in patients who are being treated palliatively. SEARCH METHODS: An electronic search was carried out of Medline, Embase, CINAHL, T he Cochrane L ibrary, Dissertation Abstracts, Cancercd and SIGLE. Review articles and reference lists of retrieved articles were hand searched. Date of most recent search: May 1999. SELECTION CRITERIA: Randomised double-blind, controlled trials comparing the use of any opioid drug against placebo for the relief of breathlessness were included. Patients with any illness suffering from breathlessness were included and the intervention was any opioid, given by any route, in any dose. DATA COLLECTION AND ANALYSIS: Studies identified by the search were imported into a reference manager database. The full texts of the relevant studies were retrieved and data were independently extracted by two review authors. Studies were quality scored according to the Oxford Quality scale. The primary outcome measure used was breathlessness and the secondary outcome measure was exercise tolerance. Studies were divided into non-nebulised and nebulised and were analysed both separately and together. A qualitative analysis was carried out of adverse effects of opioids. Where appropriate, meta-analysis was carried out. MAIN RESULTS: Eighteen studies were identified of which nine involved the non-nebulised route of administration and nine the nebulised route. A small but statistically significant positive effect of opioids was seen on breathlessness in the analysis of studies using non-nebulised opioids. There was no statistically significant positive effect seen for exercise tolerance in either group of studies or for breathlessness in the studies using nebulised opioids. AUTHORS' CONCLUSIONS: There is evidence to support the use of oral or parenteral opioids to palliate breathlessness although numbers of patients involved in the studies were small. No evidence was found to support the use of nebulised opioids. Further research with larger numbers of patients, using standardised protocols and with quality of life measures is needed.

An observational study to determine the prevalence of alcohol use disorders in advanced cancer patients.

CONTEXT: observational studies in North America suggest alcohol dependence is a common problem in advanced cancer patients and is associated with a high burden of physical and psychological symptoms. The prevalence of all types of alcohol use disorders, and the relationship between alcohol use disorders and symptoms, has not been studied. OBJECTIVES: this observational, cross-sectional study was designed to determine the prevalence of alcohol use disorders in patients with advanced cancer and establish if such patients have a higher symptom burden. METHODS: sequential patients referred to the palliative medicine team at a United Kingdom cancer centre completed the Alcohol Use Disorders Identification Test, Hospital Anxiety and Depression Scale (HADS) and Memorial Symptom Assessment Scale-Short Form (MSAS-SF). RESULTS: 120 patients participated in the study. Twenty-two (18%) patients screened positively for the presence of an alcohol use disorder. This study found no significant association between alcohol use disorders and the presence of anxiety (P = 0.38) or depression (P = 0.81) on the HADS or the global distress index subscale (P = 0.142), physical symptom distress index subscale (P = 0.734), or the psychological distress index subscale (P = 0.154) on the MSAS-SF. Current smoking status was the only independent predictor for the presence of an alcohol use disorder (P < 0.001). Seven (6%) patients screened positively for high-risk alcohol use disorders. Current smoking status (P < 0.001) and male gender (p < 0.001) were independent predictors of this problem. CONCLUSIONS: alcohol use disorders in this cohort of patients were not associated with a higher symptom burden, and the prevalence was lower than the general United Kingdom population.

The management of breakthrough cancer pain.

Breakthrough cancer pain is a heterogeneous condition, and management should involve a thorough assessment, an individualized treatment plan, and a thorough re-assessment. This article will highlight the recommendations for the management of breakthrough cancer pain from a task group of the Science Committee of the Association for Palliative Medicine of Great Britain and Ireland, and briefly review the new opioid preparations that have been developed for breakthrough pain.

Validity of the memorial symptom assessment scale-short form psychological subscales in advanced cancer patients.

CONTEXT: The Memorial Symptom Assessment Scale-Short Form (MSAS-SF) is designed to evaluate physical and psychological symptom burden in advanced cancer patients. There are no current data assessing the validity of the MSAS-SF psychological symptom scores when compared with anxiety and depression. OBJECTIVES: This observational cross-sectional study was designed to determine the relationship between the MSAS-SF subscales and the presence of anxiety and depression. METHODS: Advanced cancer patients attending a U.K. oncology center completed the MSAS-SF and the Hospital Anxiety and Depression Scale. RESULTS: One hundred twenty patients participated in the study. There was an association between the presence of anxiety and depression and the MSAS-SF global distress index. There was no association between the presence of anxiety and depression and the MSAS-SF physical symptom subscale. The MSAS-SF psychological symptom subscale was more closely correlated with anxiety than depression. CONCLUSION: These results support the validity of the MSAS-SF global distress index and psychological subscales in the assessment of patients with anxiety and depressive disorders.

Breakthrough pain: a qualitative study involving patients with advanced cancer.

CONTEXT: Breakthrough cancer pain is associated with a high burden of physical, psychological and social problems in quantitative studies. Individual experiences of living with breakthrough pain have not been studied. OBJECTIVES: This study aims to explore the individual experience of living with breakthrough cancer pain using a qualitative methodology. METHODS: In depth semi-structured interviews were conducted in ten patients with breakthrough cancer pain, and a qualitative content analysis was performed. RESULTS: The overarching themes that emerged were daily living, communication with health care professionals and management of breakthrough pain. CONCLUSIONS: Recognising the impact of breakthrough pain and the issues expressed by patients regarding communication and medication gives the clinician a framework for assessment and intervention.

Paraneoplastic Raynaud's phenomenon--good palliation after a multidisciplinary approach.

Paraneoplastic Raynaud's phenomenon is a rare complication of a number of different malignancies (carcinomas, sarcomas, lymphomas, and leukemias). We present a case of paraneoplastic Raynaud's phenomenon in a patient with non-small-cell lung cancer that was associated with significant morbidity, involved a multidisciplinary approach, and eventually responded to a specialized intervention (i.e., iloprost trometamol).