Topics in Palliative Care Medical Oncology Residents December 8, 2008

1. Topics in Palliative CareMedical Oncology ResidentsDecember 8, 2008 Jeff Myers MD, CCFP, MSEd Program Head – Supportive Care, Palliative Care and Psychosocial Oncology Odette Cancer Centre Asst Professor, Faculty of Medicine, University of Toronto

2. Curative / remissive therapy Presentation Death Hospice Palliative care

3. Palliative Care Consult Team at Sunnybrook • Inpatient consult service • Outpatient Palliative Care Clinic (OCC) • Bone Mets Clinic • CHF clinic • Kidney Care Clinic • ALS Clinic • *PCU • MDs – Wynnychuk, Chakraborty, Sirianni, Selby, Kim, Tamber

4. Ed • 63 yo male – HR prostate CA, several areas of bony mets (including L2, 3, 4 but not ischium, ilium, sacrum or right hip area) • C/o increasing right buttock pain, 8/10, deep, dull, achy in character, radiates down back of right leg, 10/10 (“more of a shooting feeling”)

5. Ed Current analgesic regimen: • Fentanyl 50 mcg/hr patch – change q72h • Tyl #3 – 1-2 po q6h prn (uses on average 5/day when pain “severe”, unsure of benefit) • Colace 100mg BID • wife reluctant to support increasing patch as her nephew is a heroin addict

6. Objectives • Improve management of nociceptive pain • Address neuropathic pain • Address fears about opioids

7. Objectives • Improve management of nociceptive pain • Address neuropathic pain • Address fears about opioids

8. Fentanyl Patch • Oral BT form not available • Onset of action, time to reach steady state and absorption highly variable • Does not allow for rapid titration • In setting of malignant pain, fentanyl only appropriate when: • pain is well controlled and unlikely to vary considerably • oral route not available**

9. Ed – Opioid Options Opioid Rotation – Correct for Cross Tolerance? • If yes, decrease by 30% • If no, leave dose the same Calculation of Breakthrough Dose: • 10% of total 24 hour dose OR • 50% of q4h dose How frequent?

10. Opioid Conversion Table * Disagreement as to appropriate equivalency Fentanyl patch 25micrograms q72hours = 50mg po morphine q24hours Methadone = complex conversion, requires license

11. 1 Percocet (5mg PO oxycodone) = 10mg PO morphine = 2 mg PO hydromorphone

12. Cost Comparison

13. Ed Fentanyl 50mcg/hr = Morphine 100mg q24h = Hydromorphone 20mg q24h

14. Ed Fentanyl 50mcg/hr = Morphine 100mg q24h = Hydromorphone 20mg q24h Hydromorph Contin 9mg BID

15. Ed Fentanyl 50mcg/hr = Morphine 100mg q24h = Hydromorphone 20mg q24h Hydromorph Contin 9mg BID Hydromorphone 2mg q1h prn

16. What was wrong with original breakthrough? Tylenol #3 – 1-2 po q6h prn 5/day

17. Opioid Conversion Table * Disagreement as to appropriate equivalency Fentanyl patch 25micrograms q72hours = 50mg po morphine q24hours Methadone = complex conversion, requires license

18. What was wrong with original breakthrough? Tylenol #3 – 1-2 po q6h prn 5/day Tyl #3 = Codeine 30mg = Morphine 3mg = Hydromorphone 0.6 mg (1/4 of reqd)

19. What was wrong with original plan for constipation? • Recent evidence suggesting no efficacy with stool softeners (docusate) • Must have laxative – maximize Senna and, if necessary, add Lactulose

20. Objectives • Improve management of nociceptive pain • Address neuropathic pain • Address fears about opioids

21. Neuropathic Pain • Disordered function of the nervous system anywhere from the periphery to the cerebral cortex; VERY common component of “malignant pain”, poorly managed • Pain may be described as sharp, burning, “pins and needles”, shooting • Treat with opioids, TCAs, anticonvulsants • Specifically – gabapentin, nortriptyline, desipramine

22. Ed • If neuropathic component of pain syndrome not fully relieved with opiate then add adjuvant • If ODB, begin with nortriptyline (25mg – 100mg) fewer anticholinergic SE than amitriptyline • Apply through Section 16 for gabapentin • PCFA = only Palliative Care MDs

23. Ed • Titrate gabapentin dose: 300mg HS for two days, 300mg BID for two days, 300mg TID, continue to titrate dose (up to 3600mg/day well tolerated; renally cleared; correct for creat clearance) • Lyrica (pregabalin) – only indications are diabetic neuropathy and post-herpetic neuralgia (dosage up to 300mg/day in 2 or 3 divided doses)

24. Pregabalin • “Lyrica” • Developed specifically to maintain biologic activity of gabapentin while improving pharmacokinetic properties • Approved in 2004 for: • Adjunct AED • Diabetic peripheral neuropathy, postherpetic neuralgia • GAD • Neuropathic pain

25. Pregabalin-pharmacodynamics • Lipophilic analogue of gabapentin • Designed to improve diffusion across BBB • lipophylic antagonist at voltage gated Ca channels (6× more potent than gabapentin)

26. Pregabalin - Dosing • Initiate 150 mg/day (divided BID or TID) • Titrate to 300 mg/day (divided TID) over 1 week • Maximum 600 mg/day • Reduce if CrCl<60 mL/min • Taper over 1 week to discontinue • Abrupt discontinuation associated with withdrawal (nausea, H/A, diarrhea)

27. Proposed Benefits of Pregabalin • Onset of action as early as 1 week • Rapid dose titration • Similar efficacy observed with BID and TID dosing • At dose > 75mg BID, more cost effective than gaba • No head to head efficacy data

28. Ed Phone follow up in 3 days, deep buttock pain somewhat improved (using 8 BTs per day), radiating pain unchanged

29. Ed Phone follow up in 3 days, deep buttock pain somewhat improved (using 8 BTs per day), radiating pain unchanged Titrate Hydromorph Contin based on BT use and add neuropathic adjuvant

30. CIPN • Taxanes – 50-70% pts experience mild to moderate numbness, tingling, burning/stabbing in hands and feet • Vinca Alkaloids – 25%; high doses associated with absent Achilles reflex, weak distal muscles, foot drop • Platinum (Oxaliplatin) – Sx can occur after prolonged therapy and may develop 3-8 weeks after last dose

31. CIPN - Tx • Cancer, 2007: One placebo controlled RCT – gabapentin (max dose 2700mg) for six weeks – no benefit • JCO, 2004: Case series, gabapentin used as secondary prophylaxis with 90% reduction in taxane-induced arthralgias/myalgias (300mg TID; 2 days prior to start to 5 days following completion of chemo)

32. Opioid Resistant Pain • Neuropathic Pain • Bony metastases • Incident Pain • Visceral Pain

33. Other options for management of complex pain • Steroids • Methadone • Bisphosphonates • Radiotherapy • Interventions

34. Interventional Pain Management Techniques • Nerve blocks • Vertebroplasty/cementoplasty • Intraspinal analgesia • epidural • intrathecal

35. Objectives • Improve management of nociceptive pain • Address neuropathic pain • Address fears about opioids

36. Which of the following is the strongest opioid? A) fentanyl B) hydromorphone C) morphine D) oxycodone E) none of the above

37. Opioid “Strength” • Patients/caregivers ask “Is this too strong?” • How do we respond?

38. Opioid “Strength” • Patients/caregivers ask “Is this too strong?” • How do we respond? • Potency (opiate receptor affinity; accounts for “difference” in # of mg) • Equianalgesic dosing • Titrate to effectiveness • “All opioids are in the same category in terms of strength. Its about figuring out which one and what dose works the best for you and your pain.”

39. Ed’s Wife: Fears About Opioids Often education and dispelling myths is all that is required to address adherence

40. Opioid Myths • MYTH 1 – opioids cause addiction • Physical dependence is an expected result of long-term opioid treatment but SHOULD NOT BE CONFUSED WITH ADDICTION • Physical dependence = withdrawal syndrome • Addiction is a chronic neurobiologic disease with genetic, psychosocial and environmental factors • Helpful to patients to differentiate reason for use ie relieving physical pain versus escaping psychological “pain”

41. Opioid Myths • MYTH 2 – opioids cause euphoria • In terminally ill patients +/- those with pain, opioids do NOT cause euphoria • Mood may improve because their pain is relieved

42. Opioid Myths • MYTH 3 – opioids = rapid tolerance • Tolerance = state of adaptation, diminished effect of drug over time • Clinically significant tolerance is unusual however in patients with progressive disease, increased levels of opioids are needed to control increased levels of pain

43. Opioid Myths • MYTH 4 opioids = respiratory depression • Respiratory depression is extremely rare • Downregulation of mu2 receptor within 48 hours of routine dosing • Opioids are a crucial part of the treatment plan for patients with end stage COPD, end stage CHF, advanced lung cancer • Naloxone (Narcan) is rarely indicated • Differentiate between opioid side effects and normal dying process

44. Nausea

45. Jack • 58 yo male; advanced colorectal; colectomy followed by FOLFOX • Further abdominal progression; current on FOLFIRI • In ER with 6 days prog increasing abdo distension and generalized abdo pain; 2 days n/v; no BM x 2 days • prn Percocet worsened nausea

46. Jack • Proximal partial SBO diagnosed, NG inserted, IV fluids started, Gravol 25-50mg IV q4h prn for nausea and morphine 5mg sc q4h prn for pain • 24 hour f/u - pt still c/o severe nausea, abdo pain somewhat improved (morphine BT x 4 given), pt has used Gravol routinely

47. Nausea/Vomiting • Vomiting centre in reticular formation of medulla • Activated by stimuli from: • Chemoreceptor Trigger Zone (CTZ) • Upper GI tract & pharynx • Vestibular apparatus • Higher cortical centres

48. Cortex CTZ GI VOMITING CENTRE Vestibular

50. D D D D 5HT 5HT 5HT 2 2 2 2 M M VOMITING CENTRE H1 H1 CB1 Effector Organs H1 CB1 M 5HT H1 2 Muscarinic Cannabinoid Dopamine Serotonin Histamine