Cancer Related Fatigue Author(s): Gary M Reisfield MD and George R Wilson MD Background While several recent studies have found fatigue to be the single most prevalent, severe, and disabling symptom in cancer patients – exceeding even pain – it remains both underrecognized and poorly treated by physicians (1). This Fast Fact reviews diagnostic and treatment approaches in the palliative care setting. Characteristics of Fatigue Cancer-related fatigue (CRF) is a persistent sense of tiredness/diminished energy related to cancer and/or its treatment, which is not relieved by rest, and which causes diminution in functional capacity and quality of life. Additional proposed ICD-10 features include: diminished concentration; diminished motivation; insomnia or hypersomnia; nonrestorative sleep; short-term memory deficits, and marked emotional reactivity to fatigue that are not primarily consequences of depression (2). Causes CRF is often multifactorial, with biochemical, physiological, psychological, and behavioral dimensions that remain poorly defined. Assessment is aimed at identifying correctable causes and determining the impact of CRF on both patients and caregivers. Common causes of CRF include: Direct effect from cancer and/or treatments Sedating medications Deconditioning Psychiatric co-morbidities (e.g. depression, anxiety) Hypoxemia, or severe anemia (Hb ≤8 g/dL) and possibly moderate anemia (Hb ≤11g/dL) Systemic infection and/or or significant organ dysfunction (e.g. heart, liver, kidney, lung) Electrolyte abnormalities (e.g. ↓Na+, ↓K+, ↓Mg++ , ↑Ca++) Nutritional imbalance/impairment Sleep disturbance Uncontrolled pain Specific Treatments Treatment should be directed toward correcting identifiable causes, e.g. elimination of sedating drugs, correction of anemia or electrolyte imbalance. NonSpecific Treatments Nonspecific treatments may be helpful in reducing fatigue, optimizing function, and promoting adaptation. Education: Educate patient/family about CRF in order to normalize the symptom and promote adaptation/adjustment through setting realistic goals; modifying and prioritizing activities; and planning activities around diurnal variations in energy levels. Exercise: Several randomized controlled trials showed benefit of exercise in managing fatigue in patients undergoing active antineoplastic treatment (3). Aerobic exercise (low to moderate intensity; progressive) is ideal, but benefits may be realized with resistance training. A reasonable goal is 20-30 minutes of (cumulative) exercise per day, 4-5 days per week.Drug Therapy: There is little good data for non-specific drug therapy in CRF. The following drugs have been used with variable success: Psychostimulants: While there is a growing literature on the use of psychostimulants for CRF, there is a lack of good controlled trails. Methylphenidate: small studies have shown some efficacy in CRF, but a recent RCT of methylphenidate, 5 mg po q2h prn (maximum dose: 20 mg/d) showed no difference from placebo at one week (4). Start with 2.5-5 mg and titrate as necessary to 15-30 mg po at 08:00 and noon. Modafanil: pilot studies indicate efficacy in the treatment of fatigue associated with depression, MS, ALS, and HIV. Potentially fewer side effects than other psychostimulants. Start with 50 mg po qam and titrate as necessary to 200-400 mg po qam. Corticosteroids: These may provide a modest duration of benefit (2-4 weeks) offset by the potential for significant toxicity. Reported regimens have included prednisone 7.5-10 mg po qd; dexamethasone 1-2 mg po qd; methylprednisolone 32 mg po qd. Megestrol acetate: Two double-blind, crossover studies showed reduction in CRF with doses of 160 mg po tid (5,6).
References
nMorrow GR, Shelke AR, Roscoe JA. Management of cancer-related fatigue. Cancer Investigation. 2005; 23:229-239. Fatigue PDQ. National Cancer Institute. Available at: www.cancer.gov/cancertopics/pdq/supportivecare/fatigue.
n Mock V. Evidence-based treatment of cancer-related fatigue. J Natl Cancer Inst Monogr. 2004; 32:112-118.
nBruera E, Valero V, Driver L, et al. Patient-controlled methylphenidate for cancer fatigue: a double-blind, randomized, placebo-controlled trial. J Clin Oncol. 2006; 24:2073-2078.
nBruera E, Macmillan K, Hanson J, et al. A controlled trial of megestrol acetate on appetite, caloric intake, nutritional status, and other symptoms in patients with advanced cancer. Cancer. 1990; 66:1279-1282.
nBruera E, Ernst S, Hagen N, et al. Effectiveness of megestrol acetate in patients with advanced cancer: a randomized, double-blind, crossover study. Cancer Prev Control 1998; 2:74-78.
nFast Facts and Concepts are edited by Drew A Rosielle MD, Palliative Care Center, Medical College of Wisconsin. For more information write to: drosiell@mcw.edu. More information, as well as the complete set of Fast Facts, are available at EPERC: www.eperc.mcw.edu.
nVersion History: This Fast Fact was originally edited by David E Weissman MD and published in January 2007. Current version re-copy-edited in April 2009.
nCopyright/Referencing Information: Users are free to download and distribute Fast Facts for educational purposes only. Reisfield GM, Wilson GR. Cancer-Related Fatigue. Fast Facts and Concepts. January 2007; 173. Available at: http://www.eperc.mcw.edu/fastfact/ff_173.htm.
nDisclaimer: Fast Facts and Concepts provide educational information. This information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Facts cite the use of a product in a dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used.
ACGME Competencies: Medical Knowledge, Patient Care Keyword(s): Non-Pain Symptoms and Syndromes
懷特新藥申請健保核價 明年Q1可望過關 自由時報-2012年12月20日 上午05:00 〔自由時報記者陳永吉／台北報導〕行政院正研議給予國內自行研發完成的新藥健保核價，估計相關辦法會在年底完成，懷特（4108）研發的「懷特血寶」主要是針對癌末病人的「癌因性疲憊症」進行治療，上個月底已經正式遞件申請健保核價，昨天懷特董事長李成家說，應該明年第一季就能核准，因此明年公司營運將比今年好。李成家表示，懷特血寶現為處分藥，是由美吾華銷售團隊在北中南各大醫院進行推廣，由於沒有健保核價，每針需自費1萬2650元，如果能取得健保核價，希望能減少病人負擔。懷特總經理黃中洋則指出，現在全台灣約有5萬名癌末病患，許多癌末病患因為化療、放療都極為痛苦，過去癌因性疲憊症因為不是疾病的一種，所以醫生無法開立處方，但根據ICD（國際疾病傷害及死因分類標準）明年最新的第十個版本，已將癌因性疲憊症列為疾病的一種，未來相關病患就有處方藥可以使用。黃中洋表示，懷特血寶4月拿到藥證後，銷售一季優於一季，且當時各大醫院主要採購藥品時間已過，只能用臨時採購來購買，所以數量不多，但明年血寶將有機會列為各醫院採購的藥品選項，如果又能獲得健保核價，相信銷售能更上一層樓。由於懷特還有多項新藥持續研發中，仍在燒錢階段，因此李成家對明年懷特能否轉虧為盈，沒有太大把握，但李成家表示，近期完成增資後，取得12億元資金，除了繼續研發新藥外，也會添購新廠房，會以既有且符合PIC/S規範的整廠為優先考慮，合併也是選項之一，將可增加懷特未來的營運動能。
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