Presentation on theme: "Cheng-Shyong Chang, MD Division of Hematology-Oncology,"— Presentation transcript:
1Pharmacological and Non-pharmacological Approach to Cancer Related Fatigue Cheng-Shyong Chang, MDDivision of Hematology-Oncology,Department of Internal MedicineChanghua Christian Hospital, Changhua, Taiwan
2Agenda Epidemiology CRF symptom and Pathophysiology Pharmacological and Non-pharmacological ApproachConclusion
4Estimated Number of Cancer Survivors in the United States From 1971 to 2006 From SEER
5Long-term trends of standardized incidence and mortality rates for all cancers in Taiwan
6Goals for Cancer Treatment Cure治癒Control控制Palliation緩解Goals for treatment of cancer depend upon patient’s status and the stage of cancer. If cancer is identified early and the patient is otherwise well, the goal is to cure cancer. If the cancer has grown to an advanced stage, the treatment goal is to prevent or slow growth/metastasis. If the cancer is in such an advanced that cure or remission is unlikely, the treatment goal is palliation.Key goals for all stages are to relieve symptoms and to maintain or improve quality of life.QOLQOLCancer treatment goals depend on the patient’s status, but quality of life is important in all stages of cancer.6
7Epidemiology -143% of cancer patients had little awareness that there were interventions to assess and treat their fatigueThat rate of fatigue as high as 90% have been reported for those undergoing treatment for various types of cancerPsychosomatics 2008; 49:283–291
8Prevalence and Intensity of Side Effects J Pain Symptom Manage 2005:30:433–442
9Frequency of Side Effects – C/T The Oncologist 2000;5:353–360
10Likelihood of Reporting Chronic Fatigue by Cancer Type
12Epidemiology - 2More clearly correlated with complaints of fatigue during breast cancer treatment are symptoms of both depression and anxietyFurther exacerbating factors for cancer related fatigue (CRF) include pain, sleep disruption, and anemiaPsychosomatics 2008; 49:283–291
14Fatigue after Treatment Evidence of fatigue rates in the range of17%–38%May be sustained several years after treatmentLonger-term fatigue may lead to adverse impacts on patients’ quality of life and a delayed return to work
16CRF Symptom Table 5 Symptom experience of cancer-related fatigue DomainSymptomPhysicalMuscle fatigueLack of strengthLowered energyCognitivePoor concentrationLimited attention spanLack of interest in activityInertiaEmotionalDiminished enjoyment of usual leaisure activitiesDecreased sense of fulfillment at workData from Butt Z, 2008; Del Fabbro E, 2006; National Comprehensive Caner Network 2008.Prim Care Clin Office Pract 36 (2009) 781–810
17The Psychological and Emotional Impact of CRF Table 1. The impact of cancer-related fatigue on emotional health in patients (n=301) undergoing treatment for cancerAspect reported in at least 50% of patientsPatients (%)Having to push yourself to do thingsDecreased motivation or interest in usual activitiesSadness, frustration, or irritability because of fatigueDiminished interest in normal activitiesMental exhaustion77625351From Curt GA, Breitbart W, Cella D et al. Impact of cancer-related fatigue on the lives of patients: New findings from the Fatigue Coalition. The Oncologist 2000;5:The Oncologist 2000;5:353–360.
18Differential Diagnosis: Fatigue or Depression? TABLE Symptoms of Global Medical Illness OverlappingWith Those of DepressionCytokine-InducedSickness BehaviorSymptoms Common toMajor DepressionAnhedoniaSocial isolationFatigueAnorexiaWeight lossSleep disturbanceDisturbed cognitionDecreased libidoPsychomotor retardationHyperalgesiaDepressed moodGuilt/worthlessnessSuicidal ideationPsychosomatics 2008; 49:283–291
19Contributing Factors for CRF Activity levelMalnutritionSleep disordersEmotional distressDepressionAnxietyNoncancer comorbiditiesEndocrine dysfunction (hypothyroidism)InfectionCardiac dysfunctionPulmonary dysfunctionRenal dysfunctionHepatic dysfunctionNeurologic dysfunctionFigure 1. Treatable contributing factors for cancer-related fatigue. Based on National Comprehensive Cancer Network guidelines .The Oncologist 2007;12(suppl 1):43–51
20Neuroendocrine: Are cytokines the culprit? Imbalances in inflammatory and inhibitory mechanisms induced by cancer treatmentPro-inflammatory responses: interleukin (IL)-1, IL-6, and Tumor Necrosis Factor- (TNF-); orPromoting anti-inflammatory actions: IL-4, IL-10, and IL-13Psychosomatics 2008; 49:283–291
21cancer related fatigue Proposed Pathophysiological Mechanisms in the Development of Cancer Related Fatiguecancer cells+↑ chronicpro-inflammatoryactivitytumor hypoxia++altered HPA-axisactivitycancer-relatedanemiaaltered 5-HTmetabolism+++cancer related fatigueEUROPEAN JOURNAL OF CANCER 4 4 ( ) –1 8 1
22Algorithm for Assessment and Management of CRF(NCCN) Fatigue level 4-10Comprehensive assessmentReview of body systemsReview of medicationsAssessment of comorbiditiesNutritional or metabolic assessment, or bothAssessment of activity levelScreening(Initial and periodic)0-10 scaleFatigue level 0-3Education and periodic reassessmentFatigue level 4-10Primary assessment:ascertain medical historyand do physical examinationDisease status and treatmentIn-depth fatigue assessmentAssessment of primary factors—ie. anaemia, emotional distress, sleep disturbance, pain, hypothyroidismManagement of fatigueRefer as indicatedReassess regularlyCorrection of possible causesSymptomatic therapyTreatment of the primary factorsManagement of comorbidities, malnutrition, deconditioningNon-pharmacologicalPharmacologicalTreat identifiedproblemsReassess degreeof fatigueReassess fatigue
23Mangements Education and counseling of patient and family Nonpharmacologic managementPharmacologic interventions
27Breast Cancer Rehab: MRM Phases I Exercises post-opShoulder shrugsShoulder rollsFront bar liftsSide bar liftsBack bar liftsActive shoulder flexionWall walking10
28Breast Cancer Rehab: MRM Phase II (3-6 weeks)Rotator cuff elevationSide triceps extensionsShoulder extensionsShoulder abductionSidelying horizontal arm liftsSidelying shoulder ERBilateral shoulder flexion
29Breast Cancer Rehab: MRM Phase III (6-10 weeks post-surgery)Continued bar lifts, ER, arm liftsInternal rotation towel stretchingForward ball stretchShoulder rotation with ballBridgingShoulder pullovers
30Evaluation of a Counseling Service in Psychosocial Cancer Care: A Pioneer Program and Study in TaiwanNai-ChihLiuDepartment of Psychology, National Chengchi University, TaipeiChia-NingLuDepartment of Psychology, National Chengchi University, TaipeiShu-HsienWangCentral Hill Medical GroupCheng-ShyongChangDivision of Hemato-Oncology, Department of Internal Medicine, Changhua Christian HospitalWei-TingWangDepartment of Psychology, National Chengchi University, TaipeiChun-YuHuangDepartment of Psychology, Chung Yuan Christian UniversityWen-YawHsuDepartment of Psychology, National Chengchi University, Taipei
31ResultsPhysical Health Component Score (PCS) and Mental Health Component Score (MCS).
36Epoetin alfa phase IV studies in tumor-associated anemia: Incremental increase in quality of life and hemoglobin (Hb) levelSpivak, Gascón, Ludwig, The Oncologist 2009;14(suppl 1):43–56
37Mean change in FACT-An total fatigue subscale score stratified by baseline total fatigue subscale scoreJpn J Clin Oncol 2009;39(3)163–168
38Analyses of recombinant erythropoietin therapy in cancer patients Spivak, Gascón, LudwigThe Oncologist 2009;14(suppl 1):43–56
39Three major concernsTumor progression resulting from stimulation of tumor cell EPO receptors,Higher risk for TE events,Shorter survival duration because of recombinant EPO itself.
40The cost-effectiveness of treatment with erythropoietin compared to red blood cell transfusions for patients with chemotherapy induced anaemia: A Markov modelS. Borg et al. Acta Oncologica, 2008; 47:
41Psychostimulants versus placebo, outcome Cochrane Database Syst Rev Jul 7;(7):CD006704
42Methylphenidate on CRF PsychostimulantsMethylphenidate on CRFMethylphenidate, a stimulant drug that improves concentration, is effective for the management of cancer related fatigue but the small samples used in the available studies mean more research is needed to confirm its role.Cochrane Database Syst Rev Jul 7;(7):CD006704
43Efficacy and Safety of Modafinil in CRF Treatment Table 1. Summary of Clinical TrialsReferencePts. (N)/MalignancyCancer TreatmentModafinilRegimenFatigue Rating (mean)BaselinePosttreatmentp ValueMorrow (2005)151/breast cancer23.5 mo post unknown treatment200 mg/day for 1 mo6.9 (0-10 scale)3.7<0.1Morrow (2006)1382/breast cancer22.8 mo post radiotherapy5.1 (BFI)3.2<0.001Morrow (2006)1430/cerebral tumorspost neurosurgical resection, radiotherapy, chemotherapy200 or 400 mg-day for 3 wk; washout 1 wk; 8-wk open extension5.2 (FSS)50.2 (MFIS)4.0 (VAFS)3.528.96.70.0003<0.00010.0005Morrow (2008)12888/unknownconcurrent chemotherapy200 mg/day or placebonumeric data/scale not publishednumeric data not published0.03BFI = Brief Fatigue Inventory; FSS = Fatigue Severity Scale; MFIS = Modified Fatigue Impact Scale; VAFS = Visual Analogue Fatigue Scale.Ann Pharmacother 2009;43:721-5.
44Bupropion/Paroxetine on CRF AntidepressantsBupropion/Paroxetine on CRFBupropionBupropion SR can reduce fatigue in cancer patients.Further placebo-controlled studies are necessary.ParoxetineThis indicated no difference between paroxetine and placebo for the treatment of CRF.The Oncologist 2007;12(suppl 1):43–51Cochrane Database Syst Rev Jul 7;(7):CD006704J Clin Oncol, 2003
45Steroids on CRF Pain improvement by methylprednisolone. OthersSteroids on CRFThis indicated no difference between progestational steroids and placebo for the treatment of CRF.Pain improvement by methylprednisolone.Cochrane Database Syst Rev Jul 7;(7):CD006704The Oncologist, 2007
46OthersL-carnitine on CRFOral levocarnitine 4 g daily, for 7 daysLevocarnitine supplementation may be effective in alleviating chemotherapy-induced fatigueThis compound deserves further investigations in a randomised, placebo-controlled studyBr J Cancer, 2002
47OthersGuarana (Paullinia cupana) improves Fatigue in Breast Cancer Patients undergoing C/TGuarana 50 mg by mouth twice daily for 21 daysGuarana is an effective, inexpensive, and nontoxic alternative for the short-term treatment of fatigue in BC patients receiving systemic chemotherapy fatigue.Alternative and Complementary Medicine. June 2011, 17(6):
48PG2 Injection An IV injectable extracted from Astragalus membranaceus (黃耆)- Polysaccharide of Astragalus membranaceus- One of the most popular TCM, and is said to benefit the deficiency of qi (vital energy) of the spleen that symptomatically presents with fatigue, diarrhea, and lack of appetiteIndication:Relieving moderate to severe cancer-related fatigue among advanced patientsThe first NDA approved botanical new drug in Taiwan
49PG2 for advanced NSCLC patients undergoing platinum-based chemotherapy ConclusionAstragalus-based Chinese herbal medicine may increase effectiveness (by improving survival, tumor response, and performance status) and reduce toxicity of standard platinum-based chemotherapy for advanced non–small-cell lung cancer.
50PG 2 phase I/II clinical trial Efficacy:Cytokine Concentrations Percentage Change from Pre-ChemotherapyN=20First Cycle (PG2 Treatment Arm)Second Cycle (No-treatment Arm)Day 8afterChemotherapyDay 14G-CSFIL-6±±±138.9 ±±±±± 631.6Relative lower IL-6 and G-CSF percent change from chemotherapy to day 8 and day 14 after chemotherapy in the PG2 treatment arm than those in the control arm was detected.The cytokine results further support that PG2 can reduce the chemotherapy –induced myelosuppression.
51PG2 Pivotal study for CRF (I) The 2nd Treatment CycleThe 1st Treatment Cycle1st week2nd week3rd week4th week3 dosesDouble-Blind, Randomized, Placebo-ControlledOpen-LabeledPG2 Treatment(n=30)PG2 plus SPC Arm1st week2nd week3rd week4th week3 dosesPlacebo plus SPC ArmPG2 TreatmentPlacebo Treatment(n=30)PopulationAdvanced progressive cancer patientsUnder standard palliative care (SPC) at hospice settingHave no further curative options available
52PG2 Pivotal study for CRF (II) The Fatigue Improvment Rate Between Cydes in PPPopulation (Baseline: Visit 1 of Cyde 1)**: P=0.020 (The comparison between two cycles in the Control Group by McNemar’s test)*有三成的有效度與Primary endpoint一致Placebo effect四成左右PG2 treatment significantly improved fatigue among cancer patients when compared with placebo treatment.The improvement of the fatigue status for the Treatment Group sustained for 8 weeks.
53PG2 Pivotal study for CRF (III) The Results of Patient’s Fatigue Improvement Evaluation at the end of Cycle 1 in PP Efficacy Subset PopulationP=0.034*29%兩組差異在三成有顯著的Placebo effect: 4成左右(reference)Method Chi-square Test (Compared between the two groups)Higher fatigue improvement response rates in the Treatment Group as 29% more than that of the Control Group at the end of the First Treatment Cycle.
54ConclusionHigh prevalence of among cancer patients receiving cancer treatmentFatigue has a significant psychosocial and economic impactCurrent therapeutic options include the assessment and treatment of any underlying causesSeveral non-pharmacological and pharmacologic approaches have the potential to provide relief for patients suffering from CRF
55ConclusionThe non-pharmacological treatment shows to be promising with measures such as cognitive- behavioral therapies (ECAM), physical exercises and maybe sleep therapies.The pharmacological treatment has shown promising results that include the use of psycho-stimulants such as methylphenidate and dexmethylphenidate, modanafil (in patients with severe fatigue), PG 2 in advanced cancer patients and ESA in patients with CT-related anemia and hemoglobin < 10 mg/dL.