Management of Cancer Pain

Transcription

1 Management of Cancer Pain Mihir M. Kamdar, MD Associate Director, Palliative Care Director, MGH Cancer Pain Clinic Depts of Anesthesia Pain/Palliative Care Massachusetts General Hospital

2 None Disclosures

3 Overview of Today s talk The Importance of the Cancer Pain Diagnosis Use Co-analgesics and Adjuvant Medications Use Opioids for Moderate to Severe pain Proper opioid selection Use of short-acting and long-acting opioids Titration, side effect management, & opioid conversion Quick Commentary: Interventional Procedures for Refractory Cancer Pain Palliative Care & Multidisciplinary Approach to Cancer Pain

4 Background and Context of Cancer Pain

5 Why is this important? Pain is a more terrible lord of mankind than even death himself - Albert Schweitzer, 1931 Cancer Pain State of the Union: 30-40% of pts with Early Disease 70-90% of pts Advanced Disease

6 How We Define Pain: An unpleasant sensory and emotional experience associated with actual or potential tissue damage Merskey, H., Bogduk, N, ed. Classification of Chronic Pain, Second Edition. IASP Task Force on Taxonomy. 1994, IASP Press: Seattle

7 How Cancer Patient s Define Pain: It s a reminder that the cancer is always there. It s a reminder that I m dying. It erodes my ability to interact with family. That s hard when I have limited time, and important things to talk about. It makes me afraid that I m going to die in agony

8 Cancer Pain Doesn t Just Impact the Individual Major Impact on Family/Caregivers Significant Healthcare Utilization: Urgent Clinic Visits ED Visits Inpatient Admissions/Readmissions for Cancer Pain Effectively Managing Cancer Pain Is Vastly Important 2

9 From Where Does Cancer Pain Arise? ~75% from Direct Tumor Effects ~25% from Cancer Therapies 1 Chemotherapy (Chemotherapy-Induced Neuropathy) Surgery (Post-Thoractomy/Mastectomy Pain) Radiation (Mucositis/Proctitis) Non-Malignant Pain 1. Bonica, J The Management of Pain. Vol. 1. Lea & Febiger. Philadelphia.

10 The Importance of Making a Cancer Pain Diagnosis

11 Diagnosing Pain **Do not just treat the symptom! Must have a diagnosis!! Diagnosis is in the History Characterize pain in full Diagnostic History Prior pain therapies Thorough Physical Exam If source unclear --> Get more data, labs/imaging etc Rule Out Onc Emergencies: Cord compression, Evolving SBO, PE etc Diagnosis --> More Effective and Targeted Therapy

12 Treating Cancer Pain

13 The WHO Cancer Pain Ladder Miguel, R. Interventional treatment of cancer pain: the fourth step in the World Health Organization analgesic ladder? Cancer Control Mar-Apr; 7 (2):

14 Non-Opioids for Cancer Pain

15 Non-Opioids Analgesics Adjuvant* Analgesics & Co-Analgesics *Drugs with other indications that may be used as analgesics - Acetaminophen - NSAIDs* - Topical Agents - Anti-Spasmodics - Corticosteroids* - Bisphosphonates/RANK-L Inhibitors* - Neuropathic Agents*

16 Opioids for Cancer Pain

17 Principles of Opioid Prescribing Derived from opium, from juice of poppy Papaver Somniferum Bind to mu, delta, and kappa opioid receptors Main effects are in dorsal horn of spinal cord Mainstay of moderate to severe cancer pain Drug selection Dosing to optimize effects Treating side effects

18 Short-Acting Immediate Release Opioids Short-Acting Opioids: Morphine (MSIR) Oxycodone Hydromorphone Fentanyl (IV or Transmucosal/Buccal/Sublingual) Oxymorphone Immediate Release Combination products (eg Opioid+Acetaminophen) Weak Mu Agonists (Tramadol & Tapentadol)

19 Long Acting Extended Release Opioids Extended Release Morphine: Morphine CR, Kadian*, Avinza* Oxycodone: Oxycodone CR Hydromorphone: Hydromorphone ER Oxymorphone: Oxymorphone ER Fentanyl: Transdermal Patch Inherently Long Acting: Methadone

20 Opioid Dosing Guidelines Use Short-acting agents for: Opioid naïve patient Dose finding total daily opioid dose Premedication prior to Incident Pain Add basal agent (long-acting opioid) in dose equal to % of 24 hour dose of PRN opioid consumed Continue PRN opioid in dose equal to 10-15% of the 24 hour dose of long-acting opioid

21 Opioid Dosing Guidelines If >3-4 doses of PRN opioid if used in 24hrs adjust long-acting opioid: Increase again by % of 24 hour dose of PRN opioid used Generally no more freq than q48-72hrs Continued evaluation & titration is critical to successful therapy Increase dose until pain relief is adequate OR intolerable and unmanageable side effects occur

22 Opioids & Special Populations Patients with Renal Insufficiency Avoid Morphine, Codeine Caution w/ Oxycodone, Hydromorphone Methadone/Fentanyl Ok Patients with bowel obstruction/unable to swallow Hydrophilic opioid elixirs (Oxycodone, Morphine, Hydromorphone) still need to get to SI Consider IV, Fentanyl, Methadone Long acting agents in patients with Gtubes Kadian/Avinza, Fentanyl Patch, Methadone

23 Case Part 1 57F w/ metastatic lung CA to chest wall - Opioid naive --> Morphine IR mg q4hrs prn - Two days later : Used total 90mg/24hrs - You decide to start a long acting agent: Morphine ER - Convert % into long-acting = 67% of 90mg is 60mg Morphone ER 30mg po q12hrs (~2/3 total daily morphine) - Continue breakthrough agent at 10-15% total daily opioid dose = Morphine IR mg q4hrs

24 Case Part 2 Same lung Ca patient Presents to clinic few weeks later Now up to Morphine ER 60mg po q12hrs Pain better, but family notes mild sedation/confusion

25 Managing Opioid Side Effects 25

26 Managing Poor Opioid Responsiveness If dose escalation adverse effects: 1. Pharmacologic strategy to lower opioid requirement Optimize non-opioid or adjuvant analgesics Intrathecal route of administration 2. Treat the side-effects 3. Opioid rotation

27 Treating Opioid Side Effects Constipation: Bowel regimen at time of starting opioid, uptitrate as needed and treat aggressively. Nausea: Tolerance may develop after few days, consider dopamine antagonist Allergy: True IgE reaction rare, more commonly non-specific histamine release Myoclonus: Dose reduction/rotation, benzo or baclofen Sedation: Tolerance may develop, consider CNS stimulant (eg Methylphenidate, Modafinil) Delirium: Dose reduction/rotation, r/o other causes, neuroleptics

28 Managing Poor Opioid Responsiveness If dose escalation adverse effects 1. Pharmacologic strategy to lower opioid requirement Optimize non-opioid or adjuvant analgesics Intrathecal route of administration 2. Treat the side-effects 3. Opioid Rotation

29 Equianalgesic Conversions Drug IV(mg) PO (mg) Morphine Oxycodone N/A 20 Hydromorphone Oxymorphone 1 10 Fentanyl 0.1 N/A Methadone* (separate conversion guidelines)

30 Incomplete Cross Tolerance Reduce equianalgesic dose by 25% 50% to account for incomplete cross-tolerance Patients will have partial but not full tolerance to a new opioid Reduce less if pain severe Reduce less if same drug by different route Reduce more if medically frail or big conversion

31 Case Part 2 Same lung Ca patient; now on Morphine ER 60mg po q12hrs but with significant sedation/confusion Decide to Rotate to Oxycodone Controlled Release Total daily Morphine ER = 120mg

32 Equianalgesic Conversions Drug IV(mg) PO (mg) Morphine Oxycodone N/A 20 Hydromorphone Oxymorphone 1 10 Fentanyl 0.1 N/A Methadone* (separate conversion guidelines)

33 Case Part 2 Total daily Morphine ER: 120mg/24hrs Morphine: Oxycodone = 3:2 120mg Morphine = 80mg Oxycodone Decrease 25-50% for incomplete x-tolerance Oxycodone 60mg/24hrs 20mg of Oxycodone CR q8hrs

34 Methadone: A Unique Opioid NMDA, NE, and 5HT effects Unique pharmacokinetics (early alpha and late beta) When used for pain: BID-TID dosing Variable and unpredictable half-life ( hrs) Steady-state in 3-5 days to up to several weeks Close monitoring needed until steady-state reached Unique equianalgesic conversion ratios QTc prolongation issues Ask for Help When Considering Methadone for Pain!

35 Common Cancer Pain Syndromes: Neuropathic & Bone Pain

36 Neuropathic Pain & Cancer Common Neuropathic Cancer Pain Syndromes: Most common post-treatment pain syndrome Chemotherapy Induced Peripheral Neuropathy (CIPN) Post-thoracotomy/ Tumor Involvement of Chest Wall Brachial/Lumbosacral plexopathies Post-Herpetic Neuralgia Neuropathic Agents Anti-depressants: TCAs, Duloxetine Anti-epileptics: Gabapentin, Pregabalin

37 Bone Pain is a Very Common: Adjuvants Can Be Particularly Helpful Corticosteroids NSAIDs Bisphosphonates - Pamidronate, Zoledronic Acid Rank-Ligand Inhibitors Radionucleides (Radium, Samarium, Strontium) Radiation Therapy Procedures: Cryoablation, Vert Augmentation for Comp Fx 37

38 Case #3: 56M with Metastatic Prostate Cancer, admitted with back pain Paged that he is reporting 10/10 mid-back pain Nurse has given him 2mg IV morphine w/o effect 1 hr ago What do you do now? Give him another 2mg IV morphine? Give him 4mg IV morphine? Switch to IV hydromorphone?

39 Managing an Acute Cancer Pain Crisis

40 Managing Pain Crises Action Depends on Patient s Response: After ~15-30 minutes: If no pain relief and no side effect: Increase dose % If partial pain relief and no side effect: Repeat Initial Dose If good pain relief: Use this dose as Breakthrough Dose and Consider PCA If no pain relief and side effects: Rotate to Different Opioid Stay at the Bedside (or Close-By), Reassess every 30min Remember IV Ketoralac if no contraindication Call for help when out of comfort range Always look for an underlying diagnosis or source of pain Moryl et al. Managing an acute pain crisis in a patient with advanced cancer: "this is as much of a crisis as a code". JAMA 2008.

41 A Quick Word on Opioids and Addiction in Cancer Pain

42 Opioid Therapy & Chemical Dependency in Cancer Patients Risk of addiction in cancer pain thought to be Low Evidence suggests that addiction or related problematic opioid use ranges from % in cancer patients 1-4 But the risk is definitely not Zero Same risk factors for abuse as in chronic non-cancer pain 5 Prior personal hx, family hx, sig anxiety/depression, PTSD etc Consider usual opioid risk mitigation measures if mod-high risk They re dying, why not just give them what they want? 1.Macaluso, C., D. Weinberg & K.M. Foley Opioid abuse and misuse in a cancer pain population. J. Pain Symptom Manage. 3: S Passik, S.D., K.L. Kirsh, M.V. McDonald, S. Ahn, et al A pilot survey of aberrant drug-taking attitudes and behaviors in samples of cancer and AIDS patients. J. Pain Symptom Manage. 19: Passik, S.D., J. Schreiber & K.L. Kirsh A chart review of the ordering of urine toxicology screen in a cancer center: do they influence on pain management. J. Pain Symptom Manage. 19: Schug, S.A., D. Zech, S. Grond, et al A long term survey of morphine in cancer pain patients. J Pain Symptom Manage. 7: Del Fabbro Assessment and Management of Chemical Coping in Patients With Cancer. JCO 2014:32;

43 What if the Pills Don t Work? Consider Interventional Therapies for Cancer Pain

44 The Cancer Pain State of the Union Continued: 50% of pts on third tier of WHO based on prospective study >2000 pts 14-24% of pts with pain despite WHO ladder Miguel, R. Interventional treatment of cancer pain: the fourth step in the World Health Organization analgesic ladder? Cancer Control Mar-Apr; 7 (2):

45 Interventional Tx : The 4th WHO Step?

46 What is Total Pain? The Importance of Palliative Care and the Multidisciplinary Approach

47 Understanding Total Pain Physical Pain Is Just One Element of Suffering Suffering: Physical* Emotional Social Spiritual Need to Attend to All Elements to be Effective No One Person Can Meet All These Needs = Multidisciplinary Approach is Imperative for Cancer Pain 47

48 The Take Home Points

49 Take Home Points: Cancer Pain Understand the pain syndrome: Must have make diagnosis! Optimize co-analgesics and adjuvant medications Use opioids for moderate to severe pain Proper opioid selection Use of short-acting and long-acting opioids Titration, side effect mgmt, & opioid rotation Remember: Interventional Therapies for Cancer Pain The Interdisciplinary Approach to Total Pain

50 Thank You!