骨転移の痛みに対する緩和ケア

⾻転移の痛みに対する緩和ケア Palliative Care for Malignant Bone Pain Yusuke Takagi. Oct 2021

Management of Malignant Bone Pain Comprehensive Assessment (Intensity, cause of pain) Treatments according to the cause ・Surgery ・Chemotherapy ・Radiation* etc * 放射性同位元素の内⽤療法も含む ・Analgesics (Non-opioid, opioids, etc) ・Bone-Modifying Agents ・Neurolytic blockade 原因に対する治療は重要だが、 治療効果が出るまでの期間の鎮痛も忘れない 1

Contents • Pharmacotherapies for Malignant Bone Pain Ø Non-Opioid Analgesics Ø Opioids Ø Adjuvant Analgesics Ø Bone-Modifying Agents • Non-Pharmacologic Interventions for Cancer Pain Ø Optimization of Daily Activities, Nursing Ø Psychotherapy (Cognitive-Behavioral Therapy, Mindfulness) ⼼理療法（認知⾏動療法、マインドフルネス） 2

Types of Pain Caused by Bone Metastasis Fracture Bone destruction Increased intramedullary pressure Somatic Pain ⾻髄内圧の上昇 Non-Opioids Opioids Nerve root compression Spinal cord compression Neuropathic Pain Adjuvant Analgesics Nerve Block 3

Non-Opioid Analgesics 1. Joishy SK et al. JPSM 1998;16:334 2. 後明ら. 医学と薬学 2007;57:343 3. Slatkin N et al. J Support Oncol 2006;4(2suppl1):15 4. Ventafridda V et al. J Int Med Res 1990;18(1):21 • Inflammatory cytokines are associated with pain in bone metastases • For somatic pain caused by bone metastases, the dose of morphine was reduced by concomitant use of NSAIDs1 • Acetaminophen is also effective for pain in bone metastases2,3 • NSAIDs tend to achieve a higher rate of analgesia than acetaminophen, but the difference is unclear4 4

Non-Opioids for Musculo-Skeletal Pain Emerg Med J. 2014 Mar;31(3):177-81. • VAS change at 30 minutes in ER patients with low back pain (blinded randomized controlled trial, N=137) 63±25 mm Acetaminophen 67±21 mm Morphine 56±23 mm NSAIDs • Efficacy of different types of analgesics does not vary significantly for non-cancerous acute musculoskeletal pain 5

Opioid Analgesics 1. Mystakidou K et al. J Opioid Manag 2005;1:204 2. Mercadante S et al. JPSM 2004;28:505 • A randomized controlled trial showed the efficacy of fentanyl patch for the pain of bone metastases1 (Control arm: codeine 120 mg/day + acetaminophen) • On the other hand, regular-dose opioids for pain at rest cannot sufficiently control motion-related breakthrough pain2 • As with non-opioid analgesics, there is no clear consensus as to which opioid is more effective 6

Adjuvant Analgesics 1. Fallon M et al. J Clin Oncol. 2016;34:550 2. Mishra S et al. Am J Hosp Palliat Care. 2012;29:177 3. Schukro RP et al. Anesthesiology 2016;124:150 4. Mercadante S et al. Tumori 2002;88:239 5. Chow E et al. Support Care Cancer 2007;15:643 • Pregabalin does not improve pain when it is used only for bone metastasis pain1 • Effective when neuropathic pain is diagnosed （Pregabalin2, Duloxetine3, and Amitriptyline4） • Steroids are effective for transient exacerbation of pain (flare) at the start of radiotherapy5 7

Pregabalin for bone metastasis pain Fallon M et al. J Clin Oncol. 2016;34:550 No significant difference from placebo when added to radiotherapy (N=233) 8

Screening for Neuropathic Pain ⼩川ら. ペインクリニック 2010;31:1187より引⽤改変 • Pain as if pricked by a needle • Pain like an electric shock • Burning and tingling pain • Severe numbing pain 針で刺されるような 電気が⾛るような 焼けるような、ひりひりする しびれが強い • Pain induced by rubbing clothing or exposure to cold air ⾐服の擦れ、冷⾵による痛みの誘発 • Decreased sensation or hypersensitivity in the painful area 痛む部位の感覚が低下、または過敏 • Red or purple discoloration of the skin at the site of the pain ⽪膚の変⾊ Neuropathic pain considered if more than one of above applies 9

Diagnosis of Neuropathic Pain Pain distribution neuroanatomically plausible & Relevant history Treede RD et al. Neurology 2008;70:1630 NO Unlikely to be neuropathic pain 痛みの範囲が神経学的に妥当 YES 感覚障害 A. Negative or positive sensory signs, confined to innervation territory B. Diagnostic test confirming lesion or disease explaining neuropathic pain 画像・⾎液・⽣検 Both applied Definite Neuropathic Pain One applied Probable Neuropathic Pain 10

Bone-Modifying Agents 1. Wong R et al. Cochrane Database Syst Rev 2002:CD002068 2. Peddi P et al. Cancer Treat Rev 2013;39:97 • The main cause of pain is bone absorption by osteoclasts, 破⾻細胞による⾻吸収 and inhibiting osteoclastic action provides pain relief Ø Zoledronic acid: Inhibits bone absorption by osteoclasts and induces apoptosis Ø Denosumab: Inhibits RANKL, which is necessary for osteoclast differentiation and maturation • Both show analgesic effects after 4-12 weeks of treatment1,2 • Also shown to prevent skeletal-related events (SREs), such as pathological fractures, spinal cord compression, and hypercalcemia 11

Non-Pharmacological Care of Pain 1. Silva EH et al. J Cancer Surviv 2019;13:97 2. Miaskowski C et al. JCO 2004;22:1713. 3. Raphaelis S et al. BMC Cancer 2020;20:559 • Pain associated with physical movement is often difficult to control with drugs, so modifications of movement is important Ø Environmental modification (installation of handrails, use of beds, etc.) 環境整備 Ø Use of orthotics 装具の使⽤ • Supporting and practicing symptom monitoring and self-management reduces pain1,2, and improves self-efficacy3 ※ Self-efficacy: the feeling of having control over one's symptoms ⾃⼰効⼒感 12

Self-Care Intervention for Bone Metastasis Pain Miaskowski C et al. JCO 2004;22:1713. • Symptom monitoring by patients (N=174) • Education and coaching by research nurses (once a week x 6 sessions) Interaction p=.026 ü Knowledge of pain and coping strategies ü Check pain scores and analgesic use ü Learn how to consult a doctor when pain relief is not sufficient 鎮痛が不⼗分な時に医師に相談する⽅法 Interaction p=.033 → Pain reduced in the self-care arm 13

Psychotherapy 1. Gorin SS et al. JCO 2012;30:539. 2. Kwekkeboom KL et al. J Pain Symptom Manage 2010;39:126. 3. Veehof MM et al, Cogn Behav Ther 2016;45:5. Methods shown to be effective in reducing pain in meta-analyses • Cognitive-Behavioral Therapy1,2 Ø Often consists of weekly sessions with a therapist and homework Ø Cognitive restructuring: Identify and correct misguided beliefs and catastrophic thinking 認知再構成 Ø Behavioral Activation: Identify and systematically perform pleasant activities ⾏動活性化 Ø Relaxation: Relaxing unnecessary physical tension Ø Pacing: Practicing a pace of life that is comfortable for oneself • Acceptance & Commitment, Mindfulness3 Ø Aims to live a life where pain is present, but not trapped by it 14