Fatigue Bigorio Professor Paddy Stone

Transcription

1 Fatigue Bigorio 2013 Professor Paddy Stone

2 Overview What is fatigue? How can fatigue be assessed? How can fatigue be treated? Guidelines?

3 Fatigue is a subjective, unpleasant symptom which incorporates total body feelings ranging from tiredness to exhaustion creating an unrelenting overall condition which interferes with individuals ability to function to their normal capacity Ream and Richardson (1996) 3

4 Prevalence Cancer-related fatigue: 40% at diagnosis 60-90% of those on treatment 30-75% of cancer survivors 84% of palliative care patients Systolic heart failure: 50-96% COPD: 43 58% End-stage renal disease: 71% 4

5 Overview What is fatigue? How can fatigue be assessed? How can fatigue be treated? Guidelines?

6 Fatigue scales Single items Uni-dimensional Multi-dimensional CRFS

7 Single item instruments NCCN guidelines ( How would you rate your fatigue on a scale of 0-10 over the past 7 days? None to mild (0 3) Moderate (4 6) Severe (7 10)

8 A systematic review of the scales used for the measurement of cancer-related fatigue (CRF) Minton and Stone Annals of Oncology 20: 17 25, 2009

9 Unidimensional scales FACT-F* EORTC QLQc30* Brief Fatigue Inventory FSS POMS

10 I have to limit my social activity because I am tired FACT-F items I feel fatigued I feel weak all over I feel listless ( washed out ) I feel tired I have trouble starting things because I am tired.. I have trouble finishing things because I am tired. I have energy. I am able to do my usual activities I need to sleep during the day I am too tired to eat I need help doing my usual activities. I am frustrated by being too tired to do the things I want to do

11 EORTC QLQc30 Did you need to rest? Have you felt weak? Were you tired?

12 Multi-dimensional scales Chalder Fatigue Scale* Fatigue Symptom Inventory Lee Fatigue Scale Multi-dimensional assessment of Fatigue Multi-dimensional Fatigue Inventory Multi-dimensional Fatigue Symptom Inventory Revised Piper Fatigue Scale Schwartz cancer fatigue scale Wu cancer fatigue scale

13 Chalder Fatigue Scale Have you had problems with tiredness? Have you needed to rest more? Have you felt sleepy or drowsy? Have you had problems starting things? Have you been lacking in energy? Have you had less strength in your muscles? Have you felt weak? Have you had difficulty concentrating? Have you had problems thinking clearly? Have you made slips of the tongue when speaking? Have you had any difficulties with your memory?

14 Pawlikowska et al Pawlikowska T et al. BMJ 1994: 308; n = 15283

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16 Prevalence (%) of "Severe fatigue" among different populations Controls Breast Prostate NSCL Advanced Stone et al Annals of Oncology, (5): 561-7

17 Cella s diagnostic criteria for Cancer Related Fatigue Syndrome A1 A2 A11 B C D Significant fatigue 5 other associated symptoms Fatigue impact Due to cancer or cancer treatment Not due to co-morbid psychopathology

18 Screening for CRFS with ChFS BFS < 11 (negative test) BFS 11 (positive test) CRFS case Non-case Total Total Sensitivity = 55/60 = 91.7% Specificity = 74 / 140 = 52.9% PPV = 55/121 = 45.5% NPV = 74/79 = 93.6% Alexander S, Minton O and Stone P Journal of Clinical Oncology 2009; 27:1197

19 Overview What is fatigue? How can fatigue be assessed? How can fatigue be treated? Guidelines?

20 Interventions for fatigue and weight loss in adults with advanced progressive illness A review of 27 Cochrane systematic reviews, 302 studies with, participants Cancer MS MND COPD CF HIV Mixed conditions Payne et al The Cochrane Library 2012, Issue 8

21 Interventions for fatigue and weight loss in adults with advanced progressive illness Cancer MS MND COPD CF HIV Mixed conditions Payne et al The Cochrane Library 2012, Issue 8

22 Exercise for cancer-related fatigue 56 studies, 4068 participants SMD -0.27, [95% CI to -0.17] Benefits of exercise on fatigue were observed for interventions delivered during or post-adjuvant cancer therapy Benefits of exercise on fatigue for breast and prostate cancer but not for those with haematological malignancies Aerobic exercise significantly reduced fatigue but resistance training and alternative forms of exercise failed to reach significance Cramp and Byron-Daniel The Cochrane Library 2012, Issue 11

23 Psycho-social interventions 7/27 studies reported a significant effect of the intervention Effect sizes varied between 0.17 to 1.07 Interventions specific for fatigue 4/5 (80%) positive Interventions not specific for fatigue 3/22 (14%) positive Brief interventions: 3 individual sessions provided by oncology nurses Goedendorp MM et al. Psychosocial interventions for reducing fatigue during cancer treatment in adults. Cochrane database of systematic reviews 2009; Issue 1

24 Erythropoietin Minton O, Richardson A, Sharpe M, Hotopf M, Stone P. Drug therapy for the management of cancer-related fatigue. Cochrane Database of Systematic Reviews 2010, Issue 7. Art. No.: CD DOI: / CD pub3

25 Methylphenidate Trials Study or Subgroup Auret 2009 Bruera 2006 Bruera 2013 Butler 2007 Lower 2009 Mar Fan 2008 Moaraska 2010 Roth 2010 Psychostimulant Placebo Std. Mean Difference Std. Mean Difference Mean SD Total Mean SD Total Weight 6.0% 15.9% 19.4% 7.9% 20.4% 8.2% 19.1% 3.2% IV, Random, 95% CI 0.03 [-0.60, 0.66] [-0.57, 0.17] 0.09 [-0.24, 0.42] [-0.87, 0.23] [-0.69, -0.05] [-0.93, 0.14] [-0.57, 0.09] [-1.77, -0.02] IV, Random, 95% CI Total (95% CI) Heterogeneity: Tau² = 0.01; Chi² = 7.79, df = 7 (P = 0.35); I² = 10% Test for overall effect: Z = 2.71 (P = 0.007) 100.0% [-0.38, -0.06] Favours treatment Favours control Minton O et al. Psychostimulants for the management of cancer-related fatigue: a systematic review and meta-analysis. JPSM 2011; 41: Minton O, Richardson A, Sharpe M, Hotopf M, Stone P. Drug therapy for the management of cancer-related fatigue. Cochrane Database of Systematic Reviews 2010, Issue 7. Art. No.: CD DOI: / CD pub3

26 Modafinil: US trial N=877 mixed solid tumours on chemotherapy Mid cycle 4 fatigue score change Beneficial effect only seen in severe fatigue (based on a 0-10 scale) 8-10 only Jean-Pierre et al. Cancer 2010;116:

27 Jean-Pierre et al. Cancer 2010;116:

28 Modafinil: UK trial Multicentre Randomized, double-blinded Placebo-controlled N = 207 Wee et al. Abstract 8 th NCRI Cancer Conference

29 Treatment effect by subgroup Wee et al

30 Meta-analysis of modafinil studies Study or Subgroup Morrow 2012 Wee 2012 Experimental Control Std. Mean Difference Std. Mean Difference Mean SD Total Mean SD Total Weight 79.8% 20.2% IV, Random, 95% CI 0.07 [-0.08, 0.23] 0.01 [-0.30, 0.32] IV, Random, 95% CI Total (95% CI) Heterogeneity: Tau² = 0.00; Chi² = 0.12, df = 1 (P = 0.73); I² = 0% Test for overall effect: Z = 0.83 (P = 0.41) 100.0% 0.06 [-0.08, 0.20] Favours [experimental] Favours [control] Acknowledgments Minton and Wee

31 Paroxetine Minton O, Richardson A, Sharpe M, Hotopf M, Stone P. Drug therapy for the management of cancer-related fatigue. Cochrane Database of Systematic Reviews 2010, Issue 7. Art. No.: CD DOI: / CD pub3

32 Progestational steroids Minton O, Richardson A, Sharpe M, Hotopf M, Stone P. Drug therapy for the management of cancer-related fatigue. Cochrane Database of Systematic Reviews 2010, Issue 7. Art. No.: CD DOI: / CD pub3

33 L-Carnitine for cancer fatigue Placebo-controlled N = 376 Primary outcome; fatigue at four weeks No benefit over placebo Cruciani et al 2012 J Clin Oncol 30:

34 Ginseng for cancer-related fatigue Placebo-controlled N = 364 Primary outcome; fatigue at 4 and 8 weeks Barton et al JNCI 2013

35 All patients

36 Patients on treatment vs patients after treatment

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39 Cancer 5 reviews, 116 studies, participants Drug treatments Methylphenidate; some evidence of benefit (Minton 2008) EPO; evidence of benefit (Minton 2008) EPA; no evidence of benefit (Dewey 2007) Paroxetine; no evidence of benefit (Minton 2008) Progestational steroids ; no evidence of benefit (Minton 2008) Modafanil benefit only in severe fatigue if at all L-Carnitine no benefit Ginseng benefit most in patients on treatment Exercise; evidence of benefit (Cramp 2008) Psychosocial interventions; 7/27 reported evidence of benefit (Goedendorp 2009)

40 Interventions for fatigue and weight loss in adults with advanced progressive illness Cancer MS MND COPD CF HIV Mixed conditions Payne et al The Cochrane Library 2012, Issue 8

41 Amantadine in MS Pharmacological treatments for fatigue associated with palliative care Peuckmann-Post et al The Cochrane Library 2010, Issue 12

42 Pemoline in MS Pharmacological treatments for fatigue associated with palliative care Peuckmann-Post et al The Cochrane Library 2010, Issue 12

43 Modafanil in MS Pharmacological treatments for fatigue associated with palliative care Peuckmann-Post et al The Cochrane Library 2010, Issue 12

44 MS 5 reviews, 23 studies, 1502 participants Drug treatment Amantadine - small inconsistent benefits Pemoline, modafanil, carnitine no benefit Non-drug treatment OT interventions some evidence of benefit for energy conservation Diet and exercise no evidence of benefit Payne et al The Cochrane Library 2012, Issue 8

45 Interventions for fatigue and weight loss in adults with advanced progressive illness Cancer MS MND COPD CF HIV Mixed conditions Payne et al The Cochrane Library 2012, Issue 8

46 MND 1 review, 2 studies, 52 participants Exercise insufficient evidence to make a recommendation (Dal Bello-Hass 2008)

47 Interventions for fatigue and weight loss in adults with advanced progressive illness Cancer MS MND COPD CF HIV Mixed conditions Payne et al The Cochrane Library 2012, Issue 8

48 COPD 3 reviews, 59 studies, 4048 participants Pulmonary rehabilitation; evidence of benefit (Lacasse 2006) Self management education programmes; 1/3 studies showed benefit (Effing 2007) Nutritional support; insufficient evidence (Ferreira 2008)

49 Interventions for fatigue and weight loss in adults with advanced progressive illness Cancer MS MND COPD CF HIV Mixed conditions Payne et al The Cochrane Library 2012, Issue 8

50 CF 1 review, 9 studies, 833 participants Physical training; insufficient evidence (Bradley 2008)

51 Interventions for fatigue and weight loss in adults with advanced progressive illness Cancer MS MND COPD CF HIV Mixed conditions Payne et al The Cochrane Library 2012, Issue 8

52 HIV 2 reviews, 21 studies, 748 participants Progressive resistive exercise; insufficient evidence (O Brien 2004) Aerobic exercise; 1/14 studies showed evidence of benefit (O Brien 2010)

53 Interventions for fatigue and weight loss in adults with advanced progressive illness Cancer MS MND COPD CF HIV Mixed conditions Payne et al The Cochrane Library 2012, Issue 8

54 Mixed conditions 1 review, 5 studies, 453 participants Hydration; insufficient evidence (Good 2008)

55 Overview What is fatigue? How can fatigue be assessed? How can fatigue be treated? Guidelines?

56 NCCN guidelines Consensus statement First published 2000, revised annually Evidence-based when possible Category 1 consensus There is uniform NCCN consensus, based on high-level evidence, that the recommendation is appropriate Category 2a consensus There is uniform NCCN consensus, based on lower-level evidence including clinical experience, that the recommendation is appropriate

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60 Summary Fatigue is common and debilitating Assess patients Treat reversible causes Consider Psycho-educational approaches Aerobic exercise Methylphenidate / Ginseng