Pain in Cancer Patient Prof. Dr. Khaled Abouelkhair, Ph. D Medical Oncology SCE, Royal College, UK Ass. Professor of Clinical Oncology Mansoura University, Egypt
Purpose • Review basic principles of pain management and analgesic therapy • Case study illustrating common pain problems and suggested management. 2
Pain in Cancer Patients Incidence • 30 -40% of patients at time of diagnosis or during disease modifying treatment • 70 - 90% in those with advanced disease 3
Pain in Cancer Patients Etiology • Direct tumour involvement: 62 -78% • As a result of diagnostic or therapeutic interventions 19 -25% – Post- radiation ( enteritis; nerve injury; osteonecrosis); Post-chemotherapy ( eg 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% 4
Types of Pain • Acute: – E. g procedural pain; pathological fracture; bowel/ureteric obstruction • Chronic • Acute on Chronic (Breakthrough pain) • Malignant; Non-Malignant 5
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 6
Goals of Pain Management • In cancer: > 80% will achieve good control 15% will have fair control < 5% will have poor or no control 7
Untreated Pain Impact on • Function • Sleep • Impaired cognitive function • Quality of life Outcomes • Depression • Decreased socialization • Increased health care utilization • Increased costs 8
“Pain is a more terrible lord of mankind than even death itself ” Albert Schweitzer 9
George • 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 10
Pain Assessment • 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? • Believe the patient “pain is what the patient says hurts…. the best judge of a patient’s pain is the patient” Bonica. 11
Pain Assessment Tools OLD CARTS O: Onset – acute vs gradual L: Location (+ radiation) D: Duration (recent/chronic) C: Characteristics (quality of pain) A: Aggravating factors R: Relieving factors T: Treatments – previously tried - response - dose/duration - why discontinued? S: Severity: Pain Scales: 0 - 10; VAS 12
Please 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/ Average No 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% 13
OPQRSTUV O NSET: When did it start? P ATTERN: How often; When; How long? Q UALITY: Describe it: sharp, dull. . . R ELIEVING/AGGRAVATING FACTORS S EVERITY: Scale of 1 - 10 T REATMENTS: What helps; For how long U NDERSTANDING: What do you think is causing it? . How does it affect you? V ALUES: Goals Of Care; expectations 14
Pain History: George • O(nset): Several months/ 2 weeks • P(attern): R shoulder/lower back pain. Constant. Increased with movement. • Q(uality): Steady aching pain • R(elief): Medication helps for about 2 -3 hrs • 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. 15 I’m not dead yet.
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 • Xrays show bony mets in shoulder and lumber spine 16
Pain Assessment • Once assessment complete: • Type of pain • Severity of Pain • Probable cause of pain • Options for pain relief 17
George – approach to treatment Develop a problem list to resolve • somatic /bone pain • acetaminophen dosing too high (~4 gms) • constipation contributing to pain intensity • compliance issues 18
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How would you better manage George’s pain? 20
Pain Management Educate patient and family: – Myth: “Save it for when it gets worse” • FACT: Treating early prevents pain • FACT: No ceiling effect of strong opioids • FACT: Tolerance is rare in Palliative Patients/PO route – Myth: “I’ll become addicted” • FACT: Addiction is rare. Boston study- 0. 03% l. Myth: Treatment worse than pain l. FACT: Side effects can be managed/treated 21
Education Constant pain requires regular dosing • avoid peaks of pain as with prn/bolus dosing • uninterrupted sleep • smoother blood levels can provide more consistent pain control • more convenient • less analgesia over time 22
Pharmacology of Pain Management • Acetaminophen • NSAIDS • Opioids 23
Adjuvants/ Co analgesics • Bisphonates/Calcitonin • Antidepressants • Anti-convulsants • Disease specific therapies: Radiation/Chemotherapy/Surgery • Steroids 24
Principles of Opioid Use • Opioids help relieve moderate to severe pain ( and dyspnea) • Episodic pain - Prescribe as needed rather than around-the-clock • 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 25
Analgesics • Step 1: Mild pain: – Acetaminophen: Max 4 gm/day • Can be very effective for mild-moderate pain if given regularly – 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 27
Opioid Analgesics: Step 2 + 3 Step 2: • Tramadol…PO, IV …variable responses…Constipation and mode changes • Codeine § About 10% of population lack enzyme to convert to Morphine § Ceiling effect: > 600 mg/day § Very constipating § Combination product or alone § 1: 10 ( Morphine: Codeine) § Sustained release preparation : 28 Codeine Contin 50, 100, 150, 200 mg
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 • Oxy. Contin 10, 20, 40, 80 mg 29
Strong Opioids • Morphine still gold standard – Concerns re: metabolites in renal failure; elderly…. Liver impairment • Hydromorphone: – More soluble. – Few metabolites – 5 x more potent than Morphine. 30
Opioid Pharmacology • Cmax = 60 mins (after PO dose) 45 mins (after SC dose) 30 mins (after IM dose) 6 mins (after IV dose) • t 1/2 = 3 -4 hours • Duration = 20 -24 hrs (immediate-release) 48 -72 hrs (sustained-release) 31
Strong Opioids • Fentanyl: Not at mu receptor. More lipophilic – – 100 x more potent than Morphine. Less constipation and nausea. Less histamine release Useful in true opioid allergy 32
Fentanyl • Transdermal Patch: 4 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 33
Opioid equi-analgesic doses • 10 mg PO morphine =5 mg SQ/IV morphine (half the oral dose) = 100 mg PO codeine (1/10) = 2 mg PO Hydromorphone (1 mg SQ) (5 x more potent) = 5 - 7. 5 mg PO Oxycodone ( 1. 5 x) = 0. 5 - 1 mg PO/pr methadone ( not Q 4 H) ( ~~10 x more potent) 34
George Proposed management strategy? 35
George • 12 -15 T#3 = – 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 36
George • Rotation to strong opioid: • Which one? • Dose: ? Equianalgesic – ? Increase dose – BT (Break Through) 37
Opioid Adverse Effects • Constipation: “ The hand that writes the opioid prescription should start the laxative” ٠ Stimulant (+/- softener) (+/- osmotic) ٠ Nausea: ٠ Approximately 50% will have some nausea in first week; 30% after that ٠ In those prone to nausea consider antiemetic (metoclopramide) 38
Opioid Adverse Effects • Neurologic: ٠ gait disturbances ٠ dizziness ٠ falls • Cognitive-behavioural effects: ٠ sedation ٠ impaired concentration • Respiratory depression: RARE 39
George: 2 days later Morphine SR 30 mg BID = 60 mg PLUS 6 BT of 5 mg = 30 mg 90 mg • Increase to morphine SR 45 mg BID • BT: 10% of TDD or 1/2 of Q 4 H dose 40
Bone Pain What role would the following play? – Radiotherapy – NSAIDs – steroids – bisphonates – calcitonin • What else might you do? 41
Bone Pain • Bone metastases are associated with bone destruction and new bone formation • Also compression or pathologic fractures • High density of pain fibres in the periosteum 42
Bone Pain • Prostaglandins: – Produce both osteolytic and osteoclastic bone changes – Sensitize nociceptors and can produce hyperalgesia 43
Management • Opioids effective BUT often need adjuvants/co-analgesics – NSAIDS – Radiotherapy – Bisphonates – Calcitonin – Systemic treatment 44
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 – “Selective” COX 2 inhibitors: Diclofenac – Nonacetylated salicylates: Diflunisal 45
Management of Bone Pain • Radiotherapy: Cochrane review – Complete pain relief in 25% at one month – Reduction in pain in further 41% – Median duration of relief: 12 weeks – In “long bones” may be just one dose • Chemotherapy • Orthopedic: Pre-emptive pinning of an incipient bone fracture; bracing; vertebroplasty 46
Incident Pain occurring as a direct and immediate consequence of a movement or activity 47
Breakthrough Pain • End of dose pain: – Usually requires dose increase regular medication • Paroxysmal/Idiopathic: – Titrate to only 1 -3 BT’s /day – BTD should be 10% of TDD/1/2 of Q 4 H • Incident Pain – Precipitant. Peaks early. Short duration – 65% last 30 minutes or less 48
Incident Pain • Bone metastases • Neuropathic pain • Intra-abdominal disease aggravated by respiration • Skin ulcer with dressing changes, debridement • Disimpaction • Catheterization 49
Approach to Incident Pain • Treat underlying problem • Radiotherapy, chemotherapy • Bisphonates • Orthopedic intervention • Nerve blocks 50
Ideal Analgesic • Easily administered • Rapid onset • Short-duration of action • In patient’s control • Before the event 51
George: 3 months later • Confused , drowsy • Not eating • Pain on any weight bearing despite recent RXT radiating into his L leg • Some myoclonus • LAB: Normal Calcium, Creatinine 200 52
George • Current medication: ٠ morphine SR 100 mg PO BID ٠ Also taking about 5 BT of 20 mg/day. ٠ 200 mg plus 100 mg = 300 mg morphine TDD What do you recommend re his pain management? 53
George ? Bone Pain with Incident Pain ? Opioid toxicity ? Neuropathic Pain ? New mets to brain or liver ? Constipation 54
Opioid Toxicity • Hyperalgesia • Allodynia • Agitated delirium • Myoclonus • Respiratory depression 55
Opioid. Toxicity Several strategies • Reduction in opioid dose by 25 - 50% • Symptomatic treatment: – Hydration – +/- haloperidol/nozinan; lorazepam/ midazolam; phenobarb • Opioid rotation 56
Opioid rotation Better balance between analgesia and unmanageable side effects • different receptors • accumulation of morphine metabolites • tolerance to a specific opioid • variability in analgesia due to incomplete cross-tolerance OR need for alternate route/more potent opioid 57
Opioid rotation For dose-limiting toxicity/unacceptable side effects and good pain control: • May be due to incomplete crosstolerance • Give approximately 50 - 75% of equianalgesic dose For pain that is not well controlled: • Switch at equianalgesic dose 58
Opioid rotation • Prospective studies: – Maddocks: Opioid rotation (morphine to oxycodone) relieved delirium in 61%; Gagnon 34%; Ashby 72% • Many retrospective studies and case studies • Now considered standard therapy 59
Opioid Rotation • Clinically important tool in achieving good pain management • Need good monitoring • Understanding and utilization of equianalgesic tables 60
Opiate conversion: Knowing he was taking Morphine 300 mg /day What dosage would you initiate the following with: – Hydromorphone? – Oxycodone? 61
Opiate conversion: • Morphine 300 ( MEDD) = mg Hydromorphone = mg Oxycodone = mcg Patch * Don’t forget to increase your breakthrough 62
Neuropathic Pain that arises from injury, disease or dysfunction in the peripheral or central nervous system. Incidence in Cancer : 30 -50% 63
Neuropathic pain in cancer Causes: • Tumour infiltration or compression of nerve, plexus, or roots • Remote effects of malignant and nonmalignant disease processes (eg diabetes) • As a result of – viral infection – treatment with surgery, radiotherapy, or chemotherapy 64
Neuropathic Pain Syndromes • Deafferentation pains: Central pain, phantom pain and post-herpetic neuralgia • Peripheral mono-neuropathies and polyneuropathies • Complex regional pain syndromes – Can develop months or years post treatment 65
Treatment of Neuropathic Pain • Treat early as central mechanisms can cause persistence of pain • Adjuvant medications are essential • Titrate one medication at a time • Push dose until pain relief or intolerable side effects seen 66
Opioids in Neuropathic Pain • Should always be tried • Individual variation • Methadone may be the most useful opioid in neuropathic pain • Some evidence for oxycodone also being more useful 67
Antidepressants in Neuropathic Pain • Tamoxifen • Tricyclic antidepressants still the best – Effective in 50 -65% of cases • Nortriptyline = amitriptyline as first line • Desipramine for those who don’t tolerate • Starting dose 10 – 25 mg • Usual therapeutic dose is 50 – 150 mg • Analgesic effect seen 4 -7 days after reaching therapeutic dose 68
Antidepressants in Neuropathic Pain • SSRI generally don’t work very well • New SSRI citalopram seems to have analgesic properties. Also fluoxetine. • SNRI venlafaxine has analgesic properties and is helpful in some • Use these agents when TCA not tolerated 69
Anticonvulsants in Neuropathic Pain • Try gabapentin first • Gabapentin has good evidence for efficacy • Most respond to 2100 – 3600 mg/day • Push dose to 6000 mg/day 80%of patient can tolerate • Others: Carbamazepine; Clonazepam; Phenytoin 70
Miscellaneous Medications • Corticosteroids useful with associated swelling and inflammation • Baclofen if associated with muscle spasm • Calcitonin 100 -200 units/day helpful with phantom limb pain and sympathetically maintained pain • ketamine • Clonidine • Mexiletine, flecanide, lidocaine 71
Topical Therapy in Neuropathic Pain • Capsaicin cream helpful in peripheral nerve pain. Need to use it consistently • ? Destruction of nerve endings • If burns on application reduce concentration for first week or add lidocaine ointment • Lidocaine 5% patch effective in some 72
Non-Pharmacological Options • physical activity program • patient education program • cognitive-behavioural therapies • other: e. g. heat/cold, massage, liniments, TENS, chiropractic, acupuncture, XRT, etc. 73
Summary • Comprehensive assessment is paramount • Avoid unnecessary delay in treating pain • Educate patient, family & caregivers • Use interdisciplinary approach • Choose medications based on stepped approach, • • as well as side effect profile Tailor medication regimens to meet individual needs and life styles Consider non-pharmacological options 74
Palliative Care • Combination of active and compassionate therapies designed to comfort and support those living with a life threatening illness • Addresses physical, psychological, social, and spiritual expectations and needs • Best delivered by an interdisciplinary team which includes the patient, family, caregivers and health providers 75
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References • Bruera E, Sweeney C. Methadone use in cancer patients • • • with pain: a review. J of PM 5(1): 127 -138, 2002 Bruera et al. A prospective open study of oral methadone in treatment of cancer pain. 9 th World Congress on Pain, 2000 Lawlor PG, Turner KS, Hanson J, Bruera E. Dose ratio between morphine and methadone in patient with cancer pain - a retrospective study. Cancer 82(6): 1167 -73, 1998 Ripamonti C. J Clinical Oncology, 1998 C Gannon. The Use of Methadone in the Care of the Dying, EJPC, 1997 R Fainsinger, T Schoeller, E Bruera. Methadone in the Management of Cancer Pain: A Review. Pain 52: 137 -147, 1993 Bruera et al. Opioid Rotation in Patients with Cancer Pain. Cancer 78(4): 852 -857, 1996 77
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