Management of Pain in Cancer Patient

1. Management of Pain in Cancer Patient Dr. Khaled Abulkhair, PhD Medical Oncology SCE, Royal College, UK Ass. Professor of Clinical Oncology Mansoura University, Egypt

2. Purpose • Review basic principles of pain management and analgesic therapy in cancer patients. • Case study illustrating common pain problems and suggested management. • Self evaluation

3. Pain in Cancer Patients What is pain? •  An unpleasant feeling occurring as a result of injury or disease, usually localized in some part of the body. • Bodily suffering characterized by such feelings. • Mental or emotional suffering; distress. Incidence: • 30-40% of patients at time of diagnosis or during disease -modifying treatment. • 70- 90% in those with advanced disease.

4. Pain is unpleasant sensation! Yet protective

5. Unlike other types of pain! Severe, sharp and short In healthy people Severe, Sharp, chronic in unhealthy patient

6. Pain in Cancer Patients Aetiology • Direct tumour involvement: 62-78% • As a result of diagnostic or therapeutic interventions 19-25% • Post- radiation ( enteritis; nerve injury; osteonecrosis) • Post-chemotherapy ( e.g. mucositis; peripheral neuropathy) • Post- operative pain- acute and chronic • Cancer induced syndromes <10% • Constipation, pressure sores, shingles • Pain unrelated to malignancy or treatment 3-10%

7. Direct Invasion by Cancer

8. Large Lytic Metastases

9. Bed Sores

10. Types of Pain • Acute: e.g. procedural pain; pathological fracture; bowel/ureteric obstruction • Chronic • Acute on Chronic (Breakthrough pain) • Malignant; Non-Malignant

11. Types of Pain • Nociceptive: Direct response to tissue injury Includes musculoskeletal (somatic) and visceral pain • Neuropathic: Pain associated with damage to the nervous system • Mixed pain syndromes

12. Impact on Function Sleep Impaired cognitive function Quality of life Outcomes Depression Decreased socialization Increased health care utilization Increased costs Untreated Pain….. Patients and caregivers need to understand that pain is important. “Pain has a tremendous impact on quality of life. There is an urgency. If pain is not controlled, their lives are out of control.

13. “Pain is a more terrible lord of mankind than even death itself ” Albert Schweitzer

14. Outcome of cancer Pain Management There’s more to cancer care than simply helping patients survive. There's more to cancer treatment than simple survival. - > 80% will achieve good control - 15% will have fair control - < 5% will have poor or no control

15. Principles of Cancer Pain Management • Start early…… • The most important step in treating pain is the assessment. • Oral route is preferred when available. Although the ratio of oral to parenteral morphine is commonly noted to be 6:1, clinical observation of chronic cases indicates that this ratio is closer to 3:1. • Choose the analgesic drug and dose to match the degree of pain suffered by the patient. • Before adding or changing to another drug, maximize the dose and schedule of the current analgesic drug.

16. For persistent severe pain, use a product with a long duration of action. Pain medications should always be administered on a scheduled basis or around the clock. It is always easier to prevent pain from recurring than to treat it once it has recurred. • As-needed dosing should be used for breakthrough pain. • if more than two as-needed doses are required for breakthrough pain in a 24-hour period, consider modifying the regimen. • Provide medications to prevent adverse events such as constipation and itching. • Use appropriate adjuvant analgesics and nondrug measures to maximize pain control.

17. Abdou • 83 year old widower: Lives alone • Ca Prostate with Bony metastases; Hx OA/ IHD/ Depression • Brought in by daughter: Won’t leave the house • Increased pain in his shoulder and lower back for 2 weeks • Constipated

18. Pain Assessment Tools • Listen carefully: What are the words used? May deny pain but will admit to having “discomfort”, “aching” or “soreness” • Do you hurt anywhere? • Are you uncomfortable? • How does it affect you? • Because pain is subjective, it is best evaluated by the patient (i.e., not a caregiver and not the health professional). • Believe the patient “pain is what the patient says hurts….thebest judge of a patient’s pain is the patient”Bonica.

19. OPQRSTUV ONSET: When did it start? P ATTERN: How often; When; How long? QUALITY: Describe it: sharp, dull...Colic RELIEVING/AGGRAVATING FACTORS SEVERITY: Scale of 1- 10 TREATMENTS: What helps; For how long UNDERSTANDING: What do you think is causing it?. How does it affect you? VALUES: Goals Of Care; expectations

20. ToolsPlease rate your pain by circling the one number that best describes your pain _____________________________________________________________ 0 1 2 3 4 5 6 7 8 9 10 What is your Pain at it’s Best / Worst/ Present/ AverageNo Pain Pain as bad as you can imagine In the past 24 hours, how much RELIEF have pain treatments or medications provided? Please circle the one percentage that most shows how much. _____________________________________________________________ 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

21. Pain History: Abdou • O(nset): Several months/  2 weeks • P(attern): R shoulder/lower back pain. Constant. Increased with movement (what would be named?). • Q(uality): Steady aching pain • R(elief): Medication helps for about 2-3hrs • S(everity): 6/10. 10/10 with movement • T(reatments): T#3 helps for about 2-3 hours. Takes about 12-15 T#3 a day • U(nderstanding): Not going on any Morphine. I’m not dead yet.

22. Examination • No evidence of fractures but clearly limited ROM in the shoulder due to pain • No vertebral tenderness and no neurological signs • Bowel and bladder function normal…yet constipated • X-rays show bony mets. in shoulder and lumber spine

23. Abdou– approach to treatment Develop a problem list to resolve • Somatic / bone pain • Acetaminophen dosing too high (~4 Gm) • Constipation contributing to pain intensity • Compliance issues

24. Do not under-estimate the patient’s condition based on his denial.

26. How would you better manage Abdou’s pain? DRUGS

27. Pain Management is not only drugs Educate patient and family: - Myth: “Save it for ..when it gets worse” • FACT: Treating early prevents pain • FACT: No ceiling effect of strong opioids - Myth: “I’ll become addicted” • FACT: Addiction is rare. Boston study- 0.03% • FACT: Tolerance is rare in Palliative Patients/PO route. - Myth: Treatment worse than pain • FACT: Side effects can be managed/treated

28. Education Constant pain requires regular dosing • Avoid peaks of pain as with prn dosing • Smoother blood levels can provide more consistent pain control • More convenient • Less analgesia over time • Maintain uninterrupted sleep

29. WHO 3-step Ladder Morphine Hydromorphone Methadone Fentanyl Oxycodone ± Adjuvants Codeine Oxycodone ± Adjuvants Acetaminophen NSAIDs ± Adjuvants

30. Drugs for Pain Management • Acetaminophen • NSAIDS • Opioids • Adjuvants/ Co analgesics • Bisphosphonates/Calcitonin • Antidepressants • Anti-convulsants • Disease specific therapies: Radiation/Chemotherapy/Surgery • Steroids

31. Analgesics • Step 1: Mild pain: • Acetaminophen: Max 2.4 gm/day Can be very effective for mild-moderate pain if given regularly…caution with Hepatic patients. • NSAIDs: Issues re GI and renal toxicity Concerns in the elderly... Non-specific: Use with GI protection COX 2 agents safer re GI morbidity and antiplatelet effects

32. NSAIDS • Both peripheral and central effects • Inhibit cyclo-oxygenase (COX) enzyme ->  Decreased prostaglandin production • Specific COX 2 inhibitors: Celecoxib, rofecoxib. Less GI effects • Less effect on platelet function • “Non-Selective” COX 2 inhibitors: Diclofenac • Nonacetylated salicylates: Diflunisal

33. NSAIDs • Ibuprofen Q4-6h, Max 2400 mg/day • Diclofenac Potassium, Cataflam, Q 8-12h, Max 150 mg/day…first day 200 mg. • Diclofenac Sodium, Voltaren, Q 8-12h, 150 mg/day. • Indomethacin Q8-12h, Max 200 / day • Naproxyn Q 12h, max1650 mg/day • Meloxicam Q24h, Max 15mg/day • Tenoxicam, Epicotel, Q24h, max 20 mg • Celecoxib Q12h, Max 400mg/day

34. Step 2 + 3 Opioid Use • Opioids help relieve moderate to severe pain ( and dyspnea in terminal patients). • Opioid receptors have been targeted for the treatment of pain and related disorders for thousands of years. • Episodic pain- Prescribe as needed • Constant pain= Regular dosing PLUS a “breakthrough” PRN dose • Right drug at the Right dose Monitor number of PRN’s used or persistent pain; Adjust as needed.

35. Opioids….blocks pain feelings • Opioid receptors have been targeted for the treatment of pain and related disorders for thousands of years. • Mu (μ), kappa (κ), and delta (δ) opioid receptors represent the originally classified receptor subtypes, with opioid receptor like-1 (ORL1) being the least characterized. • Opioids exert their analgesic effects by binding to and activating receptors that comprise part of an endogenous opioid system. • Although opioid compounds are active in the periphery as well, they produce analgesia primarily by inhibiting nociceptive transmission in the central nervous system

37. Step 2: Moderate pain Tramadol…PO, IV … • variable responses… • Max…400 mg/day • Constipation and mode changes • Myths

38. Codeine…..Co Weak Opioid • About 10% of population lack enzyme to convert to Morphine • Ceiling effect: > 600 mg/day • Very constipating • Combination product or alone • Helpful for persistent pathological cough. • 1:10 ( Morphine : Codeine) • Sustained release preparation : Codeine Contin 50,100,150, 200 mg

39. Oxycodone: Moderate ->Strong Opioid • Active at the mu and kappa receptors • Safe with decreased renal function • Potency Oxycodone 1.5 - 2 :1 Morphine • Less constipating than Codeine • Lasts ~ 4-5 hours • No ceiling effect • Alone or with ASA/Acetaminophen • OxyContin 10, 20, 40, 80 mg • Start slow stop slow

40. Strong Opioids • Morphine still is the gold standard • Concerns re: metabolites in renal failure; elderly….Liver impairment • Hydromorphone: • More soluble. • Few metabolites • 5x more potent than Morphine.

41. Opioid Pharmacology • Cmax = 60 mins (after PO dose) 45 mins (after SC dose) 30 mins (after IM dose) 6 mins (after IV dose) • t1/2 = 3-4 hours • Duration = 20-24 hrs(immediate-release) 48-72 hrs(sustained-release)

42. Strong Opioids • Fentanyl: Not at mu receptor. More lipophilic • 100x more potent than Morphine. • Less constipation and nausea. • Less histamine release • Useful in true opioid allergy

43. Fentanyl • Transdermal Patch: different strengths in mcg/hour: • 25 ~ 100 mg Morphine/day (45 -134) • 50 ~ 200 mg (135-224), 75 (225-314), • 100 ~ 400 mg (315-404 mg M/day) • Takes ~17 hours to reach steady state • Patch lasts 72 hours in 90% of patients • Sublingual, intranasal, subcutaneous, IV routes

44. Methadone • Semisynthetic used in maintenance treatment for opioid-dependent individuals as well as in patients taking opioids long term for moderate to severe pain • Has activity not only at the opioid receptors, but also at the NMDA (N-methyl-d-aspartate) receptor • Complex pharmacokinetics with extended half-life, which creates difficulties in dosing and transitioning from one opioid to another • Associated with QT prolongation and/or torsades de pointes • Effective long-acting agent; used for neuropathic pain • Start low and titrate slowly.

45. Opioid Equi-analgesic Doseshttp://agencymeddirectors.wa.gov/mobile.html • 10 mg PO morphine =5 mg SQ/IV morphine (half the oral dose) = 100 mg PO codeine (1/10) = 2 mg PO Hydromorphone (1mg SQ) (5x more potent) = 5 - 7.5 mg PO Oxycodone ( 1.5x) = 0.5- 1 mg PO/pr methadone ( not Q4H) ( ~~10 x more potent)

46. Steps for converting between opioids • Calculate total mg dose taken in past 24-hours. • Determine equi-analgesic dose. • If pain is controlled on current opioid, reduce the new opioid daily dose by 25-50% to account for cross-tolerance, dosing ratio variation, and inter-patient variability. • If pain is uncontrolled on the current opioid, increase opioid daily dose by up to 100-125%. • Titrate liberally and rapidly to analgesic effect during first 24 hours. • Monitor for adverse events and effectiveness. • Reassess the analgesic effect every 2-3 days.

47. Abdou Proposed Management Strategy?

48. Abdou • 12-15 T#3 = 350/30 mg not controlled • 3900- 4875 mg Acetaminophen plus • 360- 450 mg Codeine ~ 36- 45 mg PO Morphine TDD (total daily dose) ~ 7- 9 mg PO Hydromorphone ~ 25- 30 mg PO Oxycodone ~Patch? • Concerns re Acetaminophen dose/ Approaching ceiling Codeine

49. Abdou • Rotation to strong opioid: • Which one? • Dose: ? Equi-analgesic - ? Increase dose - BT (Break Through)

50. Opioid Adverse Effects • Constipation: “ The hand that writes the opioid prescription should start the laxative” • Stimulant (+/- softener) (+/- osmotic) • Nausea: • Approximately 50% will have some nausea in first week; 30% after that • In those prone to nausea consider anti-emetic (metoclopramide)