Presentation on theme: "Cheng-Shyong Chang, MD Division of Hematology-Oncology, Department of Internal Medicine Changhua Christian Hospital, Changhua, Taiwan Pharmacological and."— Presentation transcript:
Cheng-Shyong Chang, MD Division of Hematology-Oncology, Department of Internal Medicine Changhua Christian Hospital, Changhua, Taiwan Pharmacological and Non- pharmacological Approach to Cancer Related Fatigue
Agenda Epidemiology CRF symptom and Pathophysiology Pharmacological and Non-pharmacological Approach Conclusion
Estimated Number of Cancer Survivors in the United States From 1971 to 2006 From SEER
Long-term trends of standardized incidence and mortality rates for all cancers in Taiwan
Goals for Cancer Treatment Cancer treatment goals depend on the patient’s status, but quality of life is important in all stages of cancer. Cure 治癒 Control 控制 Palliation 緩解 QOL
Epidemiology -1 43% of cancer patients had little awareness that there were interventions to assess and treat their fatigue That rate of fatigue as high as 90% have been reported for those undergoing treatment for various types of cancer Psychosomatics 2008; 49:283–291
Prevalence and Intensity of Side Effects J Pain Symptom Manage 2005:30:433–442
Frequency of Side Effects – C/T The Oncologist 2000;5:353–360
Likelihood of Reporting Chronic Fatigue by Cancer Type Cancer 2005;104:2022–2031.
Epidemiology - 2 More clearly correlated with complaints of fatigue during breast cancer treatment are symptoms of both depression and anxiety Further exacerbating factors for cancer related fatigue (CRF) include pain, sleep disruption, and anemia Psychosomatics 2008; 49:283–291
Fatigue after Treatment Evidence of fatigue rates in the range of 17%–38% May be sustained several years after treatment Longer-term fatigue may lead to adverse impacts on patients’ quality of life and a delayed return to work
Prim Care Clin Office Pract 36 (2009) 781–810 Data from Butt Z, 2008; Del Fabbro E, 2006; National Comprehensive Caner Network 2008.
The Psychological and Emotional Impact of CRF The Oncologist 2000;5:353–360.
Differential Diagnosis: Fatigue or Depression? Psychosomatics 2008; 49:283–291
Contributing Factors for CRF The Oncologist 2007;12(suppl 1):43–51 Sleep disorders Activity level Malnutrition Emotional distress Depression Anxiety Noncancer comorbidities Endocrine dysfunction (hypothyroidism) Infection Cardiac dysfunction Pulmonary dysfunction Renal dysfunction Hepatic dysfunction Neurologic dysfunction Figure 1. Treatable contributing factors for cancer-related fatigue. Based on National Comprehensive Cancer Network guidelines .
Neuroendocrine: Are cytokines the culprit? Imbalances in inflammatory and inhibitory mechanisms induced by cancer treatment Pro-inflammatory responses: interleukin (IL)-1, IL-6, and Tumor Necrosis Factor- (TNF-); or Promoting anti-inflammatory actions: IL-4, IL-10, and IL-13 Psychosomatics 2008; 49:283–291
↑ chronic pro-inflammatory activity Proposed Pathophysiological Mechanisms in the Development of Cancer Related Fatigue EUROPEAN JOURNAL OF CANCER 4 4 ( ) –1 8 1 cancer cells tumor hypoxia altered 5-HT metabolism cancer-related anemia cancer related fatigue altered HPA-axis activity +
Algorithm for Assessment and Management of CRF(NCCN) Screening (Initial and periodic) 0-10 scale Fatigue level 0-3 Education and periodic reassessment Fatigue level 4-10 Primary assessment: ascertain medical history and do physical examination Disease status and treatment In-depth fatigue assessment Assessment of primary factors—ie. anaemia, emotional distress, sleep disturbance, pain, hypothyroidism Treat identified problems Reassess degree of fatigue Fatigue level 4-10 Comprehensive assessment Review of body systems Review of medications Assessment of comorbidities Nutritional or metabolic assessment, or both Assessment of activity level Management of fatigue Refer as indicated Reassess regularly Treatment of the primary factors Management of comorbidities, malnutrition, deconditioning Correction of possible causesSymptomatic therapy Non-pharmacologicalPharmacological Reassess fatigue
Mangements Education and counseling of patient and family Nonpharmacologic management Pharmacologic interventions
CRF Treatment Interventions J Gen Intern Med 24(Suppl 2):412–6
CRF Management Non-pharmacological interventions Karin Ahlberg, The Lancet 2003 Activity enhancementPsychosocial interventions Attention-restoring therapy Sleep therapyNutrition consultation Family interaction
Exercise and Psychosocial Intervention
Breast Cancer Rehab: MRM Phases I Exercises post- op – Shoulder shrugs – Shoulder rolls – Front bar lifts – Side bar lifts – Back bar lifts – Active shoulder flexion – Wall walking 10
Breast Cancer Rehab: MRM Phase II (3-6 weeks) – Rotator cuff elevation – Side triceps extensions – Shoulder extensions – Shoulder abduction – Sidelying horizontal arm lifts – Sidelying shoulder ER – Bilateral shoulder flexion
Breast Cancer Rehab: MRM Phase III (6-10 weeks post-surgery) – Continued bar lifts, ER, arm lifts – Internal rotation towel stretching – Forward ball stretch – Shoulder rotation with ball – Bridging – Shoulder pullovers
Evaluation of a Counseling Service in Psychosocial Cancer Care: A Pioneer Program and Study in Taiwan Division of Hemato- Oncology, Department of Internal Medicine, Changhua Christian Hospital Department of Psychology, Chung Yuan Christian University Nai-Chih Liu Cheng- Shyong Chang Chun-Yu Huang Chia-Ning Lu Shu-Hsien Wang Wei-Ting Wang Wen-Yaw Hsu Central Hill Medical Group Department of Psychology, National Chengchi University, Taipei
Results Physical Health Component Score (PCS) and Mental Health Component Score (MCS).
Results PCS MCS
CRF Management (Cont’d)
Fatigue is worse in anemic cancer patients Spivak, Gascón, LudwigThe Oncologist 2009;14(suppl 1):43–56
Epoetin alfa phase IV studies in tumor- associated anemia: Incremental increase in quality of life and hemoglobin (Hb) level Spivak, Gascón, Ludwig, The Oncologist 2009;14(suppl 1):43–56
Mean change in FACT-An total fatigue subscale score stratified by baseline total fatigue subscale score Jpn J Clin Oncol 2009;39(3)163–168
Analyses of recombinant erythropoietin therapy in cancer patients Spivak, Gascón, LudwigThe Oncologist 2009;14(suppl 1):43–56
Three major concerns Tumor progression resulting from stimulation of tumor cell EPO receptors, Higher risk for TE events, Shorter survival duration because of recombinant EPO itself.
The cost-effectiveness of treatment with erythropoietin compared to red blood cell transfusions for patients with chemotherapy induced anaemia: A Markov model S. Borg et al. Acta Oncologica, 2008; 47:
Methylphenidate on CRF Methylphenidate, 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):CD Psychostimulants
Efficacy and Safety of Modafinil in CRF Treatment Ann Pharmacother 2009;43:721-5.
Bupropion/Paroxetine on CRF 44 Antidepressants J Clin Oncol, 2003 The Oncologist 2007;12(suppl 1):43–51 Cochrane Database Syst Rev Jul 7;(7):CD006704
Steroids on CRF This indicated no difference between progestational steroids and placebo for the treatment of CRF. Pain improvement by methylprednisolone. 45 Others Cochrane Database Syst Rev Jul 7;(7):CD The Oncologist, 2007
L-carnitine on CRF 46 Others Oral levocarnitine 4 g daily, for 7 days Levocarnitine supplementation may be effective in alleviating chemotherapy-induced fatigue This compound deserves further investigations in a randomised, placebo-controlled study Br J Cancer, 2002
Guarana (Paullinia cupana) improves Fatigue in Breast Cancer Patients undergoing C/T 47 Others Guarana 50 mg by mouth twice daily for 21 days Guarana 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):
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 appetite Indication: Relieving moderate to severe cancer-related fatigue among advanced patients The first NDA approved botanical new drug in Taiwan PG2 Injection
Astragalus-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. Conclusion PG2 for advanced NSCLC patients undergoing platinum-based chemotherapy
Efficacy: PG 2 phase I/II clinical trial Relative 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. PG2 can reduce the chemotherapy –The cytokine results further support that PG2 can reduce the chemotherapy – induced myelosuppression. induced myelosuppression. Cytokine Concentrations Percentage Change from Pre-Chemotherapy
1 st week 2 nd week 3 rd week 4 th week 3 doses 1 st week 2 nd week 3 rd week 4 th week 3 doses Placebo plus SPC Arm PG2 TreatmentPlacebo Treatment (n=30) PG2 plus SPC Arm The 2 nd Treatment Cycle The 1 st Treatment Cycle 1 st week 2 nd week3 rd week 4 th week 3 doses Double-Blind, Randomized, Placebo-Controlled 1 st week 2 nd week3 rd week 4 th week 3 doses Open-Labeled PG2 Treatment (n=30) PG2 Pivotal study for CRF (I) Population Advanced progressive cancer patients Under standard palliative care (SPC) at hospice setting Have no further curative options available
PG2 Pivotal study for CRF (II) *: P=0.020 (The comparison between two cycles in the Control Group by McNemar’s test) The Fatigue Improvment Rate Between Cydes in PP Population (Baseline: Visit 1 of Cyde 1) * *
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. PG2 Pivotal study for CRF (III) Method Chi-square Test (Compared between the two groups) The Results of Patient’s Fatigue Improvement Evaluation at the end of Cycle 1 in PP Efficacy Subset Population 29% P=0.034*
Conclusion High prevalence of among cancer patients receiving cancer treatment Fatigue has a significant psychosocial and economic impact Current therapeutic options include the assessment and treatment of any underlying causes Several non-pharmacological and pharmacologic approaches have the potential to provide relief for patients suffering from CRF
Conclusion The 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.