Cinzia Brunelli

Prognostic factors in advanced cancer patients: Evidence-based clinical recommendations - A study by the Steering Committee of the European Association for Palliative Care

PURPOSE To offer evidence-based clinical recommendations concerning prognosis in advanced cancer patients. METHODS A Working Group of the Research Network of the European Association for Palliative Care identified clinically significant topics, reviewed the studies, and assigned the level of evidence. A formal meta-analysis was not feasible because of the heterogeneity of published studies and the lack of minimal standards in reporting results. A systematic electronic literature search within the main available medical literature databases was performed for each of the following four areas identified: clinical prediction of survival (CPS), biologic factors, clinical signs and symptoms and psychosocial variables, and prognostic scores. Only studies on patients with advanced cancer and survival < or = 90 days were included. RESULTS A total of 38 studies were evaluated. Level A evidence-based recommendations of prognostic correlation could be formulated for CPS (albeit with a series of limitations of which clinicians must be aware) and prognostic scores. Recommendations on the use of other prognostic factors, such as performance status, symptoms associated with cancer anorexia-cachexia syndrome (weight loss, anorexia, dysphagia, and xerostomia), dyspnea, delirium, and some biologic factors (leukocytosis, lymphocytopenia, and C-reactive protein), reached level B. CONCLUSION Prognostication of life expectancy is a significant clinical commitment for clinicians involved in oncology and palliative care. More accurate prognostication is feasible and can be achieved by combining clinical experience and evidence from the literature. Using and communicating prognostic information should be part of a multidisciplinary palliative care approach.

Pain measurement in cancer patients: a comparison of six methods

&NA; A consecutive sample of 53 chronic cancer pain patients were administered 5 different pain intensity scales: a visual analogue scale (VAS), a numerical rating scale from 0 to 10 (NRS), a verbal rating scale (VRS), the Italian Pain Questionnaire (Italian version of the McGill Pain Questionnaire) (PRI), and the Integrated Pain Score (IPS) which is an instrument designed at the Pain Therapy and Palliative Care Division of the National Cancer Institute of Milan to integrate pain intensity and duration in a single measure. These scales were administered before and after a definite therapy change. At the time of the second evaluation the patients were also administered a pain relief scale (IRS). A factor analysis of the scoring properties of these instruments revealed a high degree of association between the variables. A single factor clearly emerged explaining most of the different scales variability. A logistic regression analysis showed that VAS, NRS. VRS were more strongly associated with IRS than PRI and IPS.

A randomized, controlled clinical trial to evaluate the effects of zinc sulfate on cancer patients with taste alterations caused by head and neck irradiation

In uncontrolled clinical trials, the administration of oral zinc sulfate has been reported both to prevent and correct taste abnormalities in cancer patients receiving external radiotherapy (ERT) to the head and neck region.

Opioid purchases and expenditure in nine western European countries: ‘Are we killing off morphine?’

Background: In clinical practice the major role of opioid drugs is the management of malignant and nonmalignant pain. The primary aim of this study is to evaluate the trend in sales of four opioid analgesic drugs (codeine, tramadol, morphine, fentanyl), from wholesalers to community pharmacies, as an indicator of opioid consumption in nine European countries in 2001, 2002 and 2003. Secondary aims are to compare: (a) the amount of each drug purchased by different countries in 2003; (b) the average price for each drug in the different countries in 2003; and (c) the total expenditure for each opioid from 2001 to 2003. Methods: Data from the Statistical Report on drugs purchased by pharmacies was supplied by IMS Health, an internationally accepted information provider for the pharmaceutical and health care industries. Finding: In the period 2001-2003, while the percentage increase of purchases of fentanyl and tramadol was considerable, that of morphine was the lowest in most of the nine countries. The largest consumer of codeine was the UK and of tramadol was Belgium. The consumption of morphine was the lowest reported in all the countries together and was three times lower than that of transdermal fentanyl. There was a high variability in the costs of the opioids among the different countries. In 2003, the total expenditure on fentanyl reached the total expenditure on tramadol, followed by codeine. Morphine presents the lowest expenditure in all nine countries and over all three years. Interpretation: These results open up many questions. What factors influence opioid purchasing and costs in these European countries? It would be interesting to have the answers from those people who know the actual situation in the individual countries.

Neurotoxicity of interferon-α in melanoma therapy: Results from a randomized controlled trial

The objective of this study was to evaluate the neurologic and quality of life impact of low dose adjuvant interferon (IFN)‐α immunotherapy in patients with malignant melanoma metastatic to regional lymph nodes after radical surgery.

Is oral morphine still the first choice opioid for moderate to severe cancer pain? A systematic review within the European Palliative Care Research Collaborative guidelines project

The aim of this systematic review was to evaluate the evidence that oral morphine can be recommended as the first choice opioid in the treatment of moderate to severe cancer pain in updating the European Association for Palliative Care opioid recommendations. A systematic literature review was performed to update the 2007 Cochrane review ‘Oral morphine for cancer pain’. The literature search was conducted on MedLine, EMBASE and Cochrane Central Register of Controlled Trials databases. The search strategy, limited in time (from 1 July 2006 to 31 October 2009), was aimed to be as extensive as possible using both text words and MeSH/EMTREE terms; a hand search of the reference lists of identified papers was also performed. Randomized clinical trials, containing data on efficacy and/or side effects of morphine, were identified. Among the papers retrieved from the cited databases and the Cochrane review, 17 eligible studies, for a total of 2053 patients, and a meta-analysis were selected. These studies do not add significant information to the previous Cochrane review confirming the limitation of efficacy and tolerability data on opioid-naïve and non-selected populations of cancer patients treated with morphine and suggesting that oral morphine, oxycodone and hydromorphone have similar efficacy and toxicity in this patient population.

Which variables are associated with pain intensity and treatment response in advanced cancer patients?--Implications for a future classification system for cancer pain.

Background: This study is part of a research program to reach consensus on an international cancer pain classification system. A confirmative and explorative approach was applied to investigate which of the variables identified in the literature, by experts and patients that are associated with pain.BACKGROUND This study is part of a research program to reach consensus on an international cancer pain classification system. A confirmative and explorative approach was applied to investigate which of the variables identified in the literature, by experts and patients that are associated with pain. METHODS Data from an international, multicentre, cross-sectional study of cancer patients treated with opioids were investigated. Dependent variables were: average pain, worst pain, and pain relief (11-point Numerical Rating Scales). Forty-six independent variables were chosen based upon previous studies. Bivariate analyses identified independent variables associated with at least one of the dependent ones; 21 were included in multivariate linear regression analyses. RESULTS Two thousand two hundred and seventy-eight patients were investigated; 52% males, mean age 62 years, mean Karnofsky Performance Status 59%, mean daily opioid oral equivalent dose 341 mg. Fifty-eight percent had breakthrough pain. Mean pain scores were: average pain 3.5, worst pain 5.3 and pain relief 74%. Variables most strongly associated with these three dependent variables were: breakthrough pain, psychological distress, sleep, and opioid dose. CONCLUSIONS Breakthrough pain and psychological distress were confirmed as key variables of a future classification system. Candidate variables were: sleep, opioid dose, pain mechanism, use of non-opioids, pain localisation, cancer diagnosis, location of metastases, and addiction.

The role of paracetamol and nonsteroidal anti-inflammatory drugs in addition to WHO Step III opioids in the control of pain in advanced cancer. A systematic review of the literature

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol are used widely in the management of mild to moderate cancer pain and are frequently combined with opioids in the treatment of moderate to severe pain. Aim: To perform a systematic literature review of the evidence of the efficacy and toxicity of NSAIDs or paracetamol added to WHO Step III opioid treatment for cancer pain. Design and data sources: A systematic literature review of MedLine, EMBASE and Cochrane Central register of controlled trials database was carried out using both text words and MeSH/EMTREE terms. Results: Seven eligible papers were retrieved from the new search and five from the Cochrane review. Five of seven studies showed an additive effect of NSAIDs when combined with opioids either by improving analgesia (three studies) or by reducing the opioid dose (two studies). Paracetamol was only marginally effective in one of five trials. The study designs were not adequate to assess differences in side effects between the opioids alone and opioids in combination with NSAIDs or paracetamol. Conclusions: The evidence from the available clinical trials is of limited amount and quality, but it weakly supports the proposal that the addition of an NSAIDs to WHO Step III opioids can improve analgesia or reduce opioid dose requirement. There is insufficient evidence to support the use of paracetamol in combination with Step III opioids. Data on the toxicity of NSAIDs in this indication are insufficient owing to the small number of patients and the short duration of treatment reported in the studies.

Predicting survival in terminal cancer patients: clinical observation or quality-of-life evaluation?

Introduction: This study compares the relative prognostic power of clinical variables and quality-of-life (QoL) measures in a population of terminal cancer patients. Methods: A prospective cohort study in 58 Italian Palliative Care Units. Of the 601 randomly selected terminal cancer patients, 574 were followed until death in order to compare clinical and QoL variables (using the Therapy Impact Questionnaire (TIQ) as predictors of survival, and assess whether their combined implementation makes prediction more accurate. Results: The clinical variables most strongly associated with survival were dyspnoea, cachexia, Katzs ADL, oliguria, dysphagia, dehydration, liver and acute kidney failure and delirium (hazard ratios (HR) ranging from 2.10 to 3.01). Only the first four kept their strength once introduced in the Cox model (HRs ranging from 1.95 to 2.22). In the TIQ primary scale the strongest predictors were physical wellbeing, fatigue, functional status and cognitive status (HRs ranging from 1.42 to 1.71), but only fatigue showed an independent prognostic relevance (90% of selection). In the TIQ global scales, the Physical Symptom Index showed a stronger association with survival (HR 1.71) than the Therapy Impact Index (HR 1.47). The former marginally improved the prognostic power of the model when added to clinical variables. Internal validation confirmed that the results were not spurious. Conclusions: In terminal cancer patients, clinical variables are better predictors of survival than QoL. The large residual variability not accounted for by the model (: ≈ 70%) suggests that survival is also influenced by factors unlikely to be identified in a survey.

Which domains should be included in a cancer pain classification system? Analyses of longitudinal data

Summary Pain intensity, incident pain, pain localisation, and cancer diagnosis are important domains to include in an international cancer pain classification system. Abstract The overall aim of the present study was to further develop an evidence‐based platform for the content of an international cancer pain classification system. Data from a multicentre, observational longitudinal study of cancer patients were analysed. Analyses were carried out in 2 samples: (A) Cross‐sectional data of patients on opioids at inclusion, and (B) patients just admitted to palliative care. Outcome measures in the models we investigated were pain on average, worst pain, and pain relief at inclusion, and at day 14, respectively. Uni‐ and multivariate regression models were applied to test the explicative power on pain outcomes of a series of known pain domains, including incident pain, psychological distress, neuropathic pain, pain localisation, sleep disturbances, total morphine equivalent daily dose (MEDD), and cancer diagnosis. In the 2 analyses, 1529 (A) and 352 (B) patients were included, respectively. Incident pain, pain localisation, MEDD, use of nonsteroidal antiinflammatory drugs, and sleep were associated with one or more of the pain outcomes in analysis A, while initial pain intensity, initial pain relief, incident pain, localisation of pain, cancer diagnosis, and age were predictors in the longitudinal analysis. Identified domains explained 16% to 24% of the variability of the pain outcome. Initial pain intensity emerged as the strongest predictor of pain outcome after 2 weeks, and incident pain was confirmed to be a relevant domain. The regression models explained only a minor part of the variability of pain outcomes.