Thinking Outside the Box for the Treatment of Cancer Pain

Transcription

1 Thinking Outside the Box for the Treatment of Cancer Pain Suzette Walker, MSN, FNP-C, AOCNP DNPc Co-Director Symptom Management & Supportive Care Program University of Michigan Comprehensive Cancer Center Emily Mackler, Pharm.D., BCOP Clinical Pharmacist in Hematology Oncology University of Michigan Comprehensive Cancer Center

2 1. Review the etiology, incidence and consequences of cancer related pain 2. Summarize strategies for providing cancer pain management 3. Discuss cancer pain cases and innovative approaches to treatment

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4 Physical Functional Pain Social Emotional Spiritual

5 30 40% of patients report moderate or severe pain occurring at the time of diagnosis % of cancer pain occurs in patients with advanced or terminal cancer 80% of patients have more than one pain 33% of patients have four or more pains Oncology Channel. McPherson ML. Oncology Boot Camp: Pain Mngmt 2010

6 Somatic pain Visceral pain Bony metastasis Mucositis Plexopathies Nerve or spinal cord compression Neuropathic pain

7 Nociceptive Pain Neuropathic Pain Somatic Visceral Peripheral or Central Dull, aching, welllocalized Skin, bone, joint, soft tissues. Bone mets, factures Diffuse, deep, aching, gnawing. Poorly localized. Bladder distension/cramping, intestinal distension, constipation, angina Burning, shooting, pricking, paresthesias, dysesthesias. Phantom limb pain, spinal cord injury pain, stroke, diabetic neuropathy, postherpetic neuralgia Johnson BW, et al. In: Cancer Pain Management. 1997;31-8. McPherson ML. Oncology Boot Camp: Pain Mngmt 2010

8 Peripheral neuropathy Drug induced (including chemotherapy) Herpes zoster Tumor nerve infiltration Post-op neuropathies Phantom pain Motor neuropathy

9 Bone Fractures Bone metastasis Medications

10 Patients and families fear pain Interferes with activities Interferes with sleep Leads to depression and other mood disturbances Disrupts interactions with family and friends Affects motivation and overall feelings of wellbeing

11 PQRST Believe patient has pain Palliative factors - What makes the pain better/worse? Quality - Describe the pain Radiation - Where is the pain? Severity - How does this pain compare with other pain you have experienced? Temporal factors - Does the intensity of pain change over the course of the day? K Foley. Principles and Practice of Oncology

12 What would you like to do that you can t do now because of your pain? Improve Performance Improve Quality of life Interact with family and friend Sleep better Improve comfort

13 Energy conservation Physical Therapy Massage Heat or ice Imagery Relaxation training Spiritual consult Social work consult

14 Nociceptive Pain Antineoplastic treatment Conventional analgesics Opioids, nonopioids, co-analgesics Metastatic bone pain NSAIDS, bisphosphonates Neuropathic Pain Opioids Co-analgesics (anticonvulsants, antidepressants) American Pain Society. Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain, 6 th ed., McPherson ML. Oncology Boot Camp: Pain Mngmt 2010

15 Anesth Analg. 1993;77:

16 Methadone is least expensive Also NMDA receptor antagonist enhanced neuropathic effects? Reports of deaths, ODs, & cardiac arrhythmias EKG monitoring required Carefully select dosing Morphine SR: MS Contin, Oramorph SR, Kadian Oxycodone SR: Oxycontin Fentanyl patches: Duragesic Short-acting opioid, but released continuously Hydromorphone: Exalgo (REMS) Once daily administration Oxymorphone: Opana ER Oxycodone is metabolized in the liver to oxymorphone Tapentadol ER: Nucynta ER (REMS) Mu-opioid receptor agonist & norepinephrine reuptake inhibior (NRI) Max daily dose = 500 mg/day No standard dosing conversions exist Caution with SSRIs and SNRIs

17 Morphine tablets, solution, and rectal Oxycodone tablets and solution Hydromorphone tablets Oxymorphone tablets Fentanyl Oral transmucosal lozenge, on a stick (Actiq) - REMS Buccal tablet (Fentora) REMS Buccal soluble film (Onsolis) REMS Sublingual tablet (Abstral) REMS Nasal spray (Lazanda) REMS Tapentadol (Nucynta) tablets - REMS

18 Oral long-acting opioid is basal therapy Rapid/quick-onset, short-acting analgesic used for breakthrough pain Dosing: 10% - 15% of the total daily dose Example: MS Contin 90 mg PO q12h Total daily dose = 180 mg/day of oral morphine Morphine IR 20 mg PO q2h prn

19 Renal impairment Active metabolites: propoxyphene, meperidine, morphine Less active metabolites: oxycodone, hydromorphone Inactive metabolites: fentanyl, methadone Liver impairment all are metabolized Traditionally, adjustments are made in 25% increments Opioids and REMS Financial insurance, etc.

20 Mu opioid partial agonist/kappa antagonist Buprenorphine transdermal system (Butrans) Mu opioid partial agonist and opioid antagonist Buprenorphine and naloxone sublingual tablets and film (Suboxone) Lidocaine (IV) Ketamine (IV and PO) Topical agents

21 Buprenorphine transdermal system (Butrans) Q7day patch (5, 10, 20 mcg/hr) Maximum dose = 20 mcg/hr due to QT prolongation Potentially less side effects Potential to precipitate withdrawal in patients on opioids

22 Buprenorphine and naloxone sublingual tablets and film (Suboxone) Do not recommend for treatment of cancer pain For patients with cancer pain requiring opioids, careful observation should occur while titrating off (and beginning opioid therapy)

23 Sharma S, et al. J Pain Symptom Manage 2009 Phase II pilot of IV lidocaine for opioid-refractory pain in cancer patients Dose: 2 mg/kg IV bolus followed by additional 2 mg/kg IV over one hour Mean onset = 40 minutes Mean duration of pain control = 9 days (compared to 4 days with placebo) Significantly lower pain score compared to placebo (1.44 vs 5.2) & less rescue meds used ADRs: sedation, light-headedness, tinnitus & headache.

24 Case reports exist with the use of continuous IV therapy Safety: seizures, cardiac toxicity (role for levels?) Monitoring should occur and pain service (or experienced team) should be involved

25 Dosing (no standard): Test dose of mg/kg IV over 10 minutes, Continuous IV: mg/kg/hr IV continuous infusion with potential dose increase to 1.5 mg/kg/hr, titration every 6 hours as needed Bolus IV: may be administered q 6 to 8 hrs Oral: 0.5 mg/kg q 8 12 hr Bioavailability approx 20% with peak 30 min & t½ 5 hrs

26 Decrease in scheduled opioid regimen (with breakthrough available) Varying data regarding benefit ADRs: hallucinations, agitation, tremors, vivid dreams Supportive therapies Benzodiazepines (pscyhomimetic effects) Scopolamine (increased secretions) Monitoring should occur & pain service (or experienced team) should be involved

27 Anti-inflammatory Diclofenac (Voltaren) 1% gel apply 2 4 x daily to affected area Ketoprofen gel 5% - 20% apply 3 x daily to affected area Indomethacin 50 mg/ml/piroxicam 10 mg/ml gel apply BID Neuropathic Lidocaine 2.5%/Priolocaine 2.5% (Emla) cream apply TID Ketamine 5% - 10% gel apply TID Amitriptyline 2%/Ketoprofen10%/Lidocaine 2% gel apply TID Gabapentin 3%/Lidocaine 2%/Ketoprofen 10% apply TID

28 56 year old male with primary liver tumor PMH-hepatitis C, alcohol abuse Pain score a 12 on a 10 point scale Fentanyl 200mcg/hr Dilaudid 2mg four times a day, and oxycodone 5mg four times a day Can not sleep Not hungry Constipation Docusate Sodium (Colace) PRN Financial constraints

29 Pain control M.S. Contin- 260mg PO BID MSIR 30mg-60mg PRN Constipation Lactulose Senna Sleep Mirtazapine (Remeron)

30 Pain significantly improved, PS greatly improved Pain control and improved sleeping pattern Currently on M.S.Contin 400 mg PO TID MSIR 30-90mg PRN Constipation improved Gained 10 pounds

31 Enhance efficacy of opioids Pain that cannot be blocked by opioids alone Neuropathies Inflammatory pain Bone pain Bony metastasis

32 NSAIDs Bisphosphonates - Pamidronate & Zoledronate RANK ligand inhibior Denosumab (XGEVA) Corticosteroids Calcitonin Local radiation therapy Cancer chemotherapy directed to primary tumor Joint replacements, resection, or nailing

33 Antidepressants Tricyclic Antidepressants (TCAs) Nortriptyline Desipramine Amitrityline Selective serotonin and norepinephrine reuptake inhibitors (SNRIs) Duloxetine Venlafaxine Bupropion Anticonvulsants Gabapentin Pregabalin Carbamazepine Topical Agents Lidocaine 5% patch Lidocaine cream (EMLA) Compounded creams Baclofen, amitriptyline, ketamine Gabapentin containing Capsaicin Opioids Tramadol

34 MOA inhibit reuptake of norepinephrine and serotonin Nortriptyline, desipramine Amitriptyline MOST anticholinergic effects (sedation, blurred vision, weight gain, urinary retention) Start low (10 25 mg QHS) Caution if concurrent use with tramadol, tapentadol (methadone?) Caution in cardiovascular disease (consider EKG)

35 MOA: inhibit reuptake of biogenic amines, primarily norepinephrine Duloxetine Starting dose 30 mg daily, increase to 60 mg daily after 1 week (max = 60 mg BID) Venlafaxine Starting dose 37.5 mg QD or BID, increase by 75 mg weekly (max = 225 mg) Withdrawal symptoms pronounced

36 49 year old with breast cancer and bone mets. Pain in right hip resolved with RT. (6/11) Monthly bisphosphonate Has all over pain Does not like the feeling of opioid therapy NSAIDs upset her stomach Duloxetine 20mg started (7/11) Complete control of pain Patient believes it stopped the hot flashes

37 MOA: bind to the α2-δ subunit of voltage-gated calcium channels, decreasing release of glutamate, norepinephrine, and substance P Dosing Starting dose in elderly 100 mg qhs Younger patients, 300 mg qhs Titrate q1-7 days, titrate based on pain relief Maximum 3600 mg/day Renal failure dose DECREASE Adequate trial 1-2 months Elderly dizziness, somnolence

38 MOA: same as gabapentin Dosing Start at 150 mg/day, increase to 300 mg/day within 1 week Maximum = mg/day Renal failure dose DECREASE We see a lot of edema

39 57 year old with metastatic prostate cancer Tx d on an investigational agent that caused severe neurotoxicity requiring admission (7/10) Referred to the Symptom Management clinic after no response to Lyrica Severe life style limitations. Not sleeping. Crippling pain Gabepentin started Oxycontin and oxycodone started

40 Over time Gabapentin increased to 1200mg po TID Nortriptyline 50mg po QHS Sleep pattern improved Oxycontin 60mg po BID using Oxycodone for breakthrough Pain improves Can walk Can play guitar again

41 Began having dysphasia and weight loss, progressed to eating just liquids Esophagectomy due to complete stasis of the esophagus Gaines 25 pounds Returns to work Continues to be in good pain control and neuropathies well controlled

42 Constipation Bowel regimen always needed Nausea Haloperidol (Haldol) Pruritus Delirium Think haloperidol (Haldol) Respiratory depression Rare Sedation Think methylphenidate (Ritalin)

43 65 yr old with metastatic melanoma Failed chemotherapy, beginning RT to abd for large pelvic tumor causing significant lymphedema and DVT Severe abd and leg pain Currently on MS Contin 30mg am and early afternoon with 45 mg at HS Hallucinates, confused, nightmares, paranoid activities, can not have meaningful conversation with family

44 Haldol 0.5mg po Pain service referral to evaluate if intervention an option so opioids can be reduced or stopped Home safety addressed

45 Hallucinations, paranoia, confusion resolved within two doses Patient remains with some sedation but pain score improved Haldol scheduled BID Now that she is alert she is able to express complaints of neuropathy Neurontin started, increased over time with excellent improvement

46 NSAIDS GI upset Kidney dysfunction Acetaminophen (Tylenol) Liver American Liver Foundation recommends that people not exceed 3 grams of acetaminiphen/day for any prolonged period of time SNRIs Tricyclic Anticholinergic Steroids

47 37 year old with stage IV follicular lymphoma. On maintenance therapy Referred for pain management and uncontrolled nausea Fentanyl 25mcg/hr Compazine 10mg po PRN

48 Tired everything known to us for nausea. Granisetron 1mg po BID Fentanyl 125mcg/hr, will not take anything for breakthrough Multiple referral to social work for depression Did not tolerate any of the medications Sleep/nightmares Remeron 7.5mg po QHS

49 Continues to complain of ongoing pain Reports in clinic that he fears he will hurt his wife and children Urgent psych consult obtained Patient does not follow with psych as requested Will see social work

50 Physical Functional Pain Social Emotional Spiritual

51 Pain management should involve a multidisciplinary team Multiple aspects to consider Medications and medication side effects and interplay Concomitant diseases Involvement of multiple teams Social aspects Spiritual aspects Financial restraints And more and more and more.

52 Always believe that pain is real Reassure that they are never alone, be available Describe that this is a team approach Be honest about the reality of emotional responses to pain and the medications used to treat Express that there is always more that can be done

53 Suzette Walker Emily Mackler