Cancer Pain Management John On-Nin Wong, M.D., Ph.D. Dept. of Pain Management and Palliative Medicine St. Martin De Porres Hospital

Cancer Pain Management John On-Nin Wong, M.D., Ph.D. Dept. of Pain Management and Palliative Medicine St. Martin De Porres Hospital

WONG

1982 1982

30% 70-90% 30-40% 40% 50 80% ( 40 100% ) ECOG ( US survey ) : van Roenn 1993 1308 1308 67% 36% 1177 85% 1998 1998 38% 38% 69%

Pain in Cancer ( Terminal Stage ) Cartwright et al. ( 1973 ) 87 % Foley ( 1979 ) 60 % Pannnuti et al. ( 1979 ) 65 % Parkes ( 1978 ) 65 % Twycross ( 1974 ) 80 % Wilkes ( 1974 ) 60 % Huang ( 1993 ) 78 % Wong ( 2003 ) 81 %

WHO WHO 70 70 90% 90% 100% ( Undertreated )

20

WHO 1978-97 ( 20 )

74.95 Morphine consumption 1998 (kg/mill. inhab.) 28.20 30.72 33.54 25.03 Austria USA France UK 14.83 6.28 Germany Japan 0.61 0.08 China Taiwan

1988-2001 (1/120) (1/33) (1/5)

1991-1995 1995

1987-2002

1987-2002

1987 1987 12.2mg 12.2mg 2002 2002 257.7mg 257.7mg 16 16 20 20 1/28 1/28 1/12 1/12 1/3 1/3 1989 1989 1999 1999 1999 1999 ( Transdermal Transdermal Fentanyl Fentanyl ) 1995 1995

1. WHO ( Teoh N, et al. 1992 ) 2. ( Takeda F 2001 ) 3. ( Huang Y 2001 ) 4. ( ( Ger LP, et al. 2000 )

WONG

1. 2. 3.

(Nociceptive) ( ) ( Somatic ) ( Visceral ) (Neuropathic)

( Total Suffering ) ) (Total Pain) ( Total suffering ) ( Total care ) ( Pain ) ( Physical symptoms ) ( Psychological problems ) ( Social difficulties ) ( Spiritual concerns ) ( Cultural factors )

( Total suffering ) = ( Pain ) + ( Physical symptoms ) + ( Psychological problems ) + ( Social difficulties ) + ( Spiritual concerns ) + ( Cultural factors )

1. 2. 3.

1. 2. 3. 4. 5. P.E. 6. 7. 8.

1

2

3 VAS

Brief Pain Inventory ( Short Form ) ( Short Form )

Initial Pain Assessment Tool

WONG

1. 2. 3. 4. 5. 6.

( Modify the source of pain) ( Alter central perception of pain ) ( Block transmission of pain to the CNS )

5-Prong Approach to Cancer Pain

Therapeutic Pain Intervention Options I. Pharmacologic II. Nonpharmacologic Opioids NSAID s Steroids Neurolytic blocks Peripheral nerve blocks Autonomic blocks Antidepressants Spinal injections Anticonvulsants Cryoablation / RF lesioning -blockers Neurosurgical ablation Antispamodics Non Non-neurolyticneurolytic blocks Antiemetics etc. Trigger point injections Perineural steroid injections Sympathetic blocks Electrical stimulation Biofeedback & relax. techniques Physical & psychiatric therapies Other alternative therapies

3. 2. 1.

Cancer Pain Management

(1) ( analgesics ) ( dose ) ( route ) ( interval ) ( persistent pain) ( breakthrough pain )

(2) ( titrate )) Stm

(3) 1. ( WHO 3-step 3 analgesic ladder ) 2. ( Individualized ) 3. ( Non-invasive ) 4. ( Equianalgesic table ) 5. ( Addiction ) ( Tolerance )

WHO By the mouth ( or by non-invasive routes ) By the clock By the ladder For the individual Attention to detail

Three-step analgesic ladder

Acetaminophen ( Non-steroidal anti-inflammatory inflammatory drugs ) IV/IM: Voren, Aspegic, Tilcotil, Ketorolac COX-2 2 inhibitors: Meloxicam ( Mobic ), Celecoxib ( Celebrex ), Rofecoxib ( Vioxx )

Analgesic Oral dose ( mg ) Parenteral dose ( mg ) Codeine 100 50 Dihydrocodeine 50-75 N/A Hydrocodone 15 N/A Oxycodone 7.5-10 N/A Not recommended for routine use: Propoxyphene, Butorphanol, Nalbuphine, Buprenorphine,, etc.

(1) * Meperidine ( Demerol, Pethidine ) toxic metabolite ( Normeperidine ) * Methadone toxic accumulation

(2) Analgesic Oral dose (mg) (mg) Parenteral dose Morphine 15 5 Oxycodone 7.5-10 [ 3.75-5 ] Hydromorphone 4 0.75-1.5 Fentanyl N/A ( OTFC ) [ 50 mcg/h, q72h ] (TTS-F F )

Morphine [ MSIR ] PO, PR, IV, SC, IT. 35% 20-25 % 34 M-6-G, M-3-G ( Neuroexcitatory toxicity )

Morphine [ Controlled- Release, MST,, MS contin,, MXL ] ( Contin delivery system ) ) 1 2-3 12 / 24 24 PRN ( rescue dose ) ) (MSIR) MSIR) ( MST )12) 12 1/3 ( titration ) ) (1) ( MSIR ) 2 ( MST ) (2) PRN 1/3 1/3

Oxycodone ( OxyIR, OxyFast ) (1) ( Ceiling ) ) (2) (3) 60% 60 80 % %

Oxycodone Release, OxyContin ) ( Controlled- ( AcroContin delivery system ) ) 0.5 1 12 PRN ( Rescue dose ) ) (OxyIR) 12 1/3 ( Titration ) 2

Hydromorphone ( Dilaudid, Hydromorph Contin ) PO PR IV SC 1 4 2 6

[FentanylFentanyl Transdermal system, Duragesic ] Opioid receptors. 1 12-24 24 2 48-72 3 17-24

Structure of Durogesic

Absorption and distribution

Serum Concentration of Fentanyl

Titration of Durogesic

( 2 ) [Fentanyl Transdermal system, Duragesic ] ( Equianalgesic dosing ) ) 1 Donner 25ug/h = 30-90 mg 60mg 2 ug/h dose of Duragesic = 1/2 mg/day dose of Morphine 25, 50, 75, 100 ug/h 1 NPO 2 3 4

Transdermal Fentanyl ( Durogesic Patch )

Conversion table from Donner

Conversion table from Grond

Oral Transmucosal Fentanyl Citrate ( OTFC ) [ Actiq, Oralet ] ( breakthrough pain ) ( buccal ) 15 25% ( buccal ) 25% ( oral ) 5-15 60-120 ( Titration ) )

( Opioids ) opioid 1. Butorphanol 2. Nalbuphine 3. Pentazocine Opioid Opioid Buprenorphine

( Appropriate dose ) ( Maximal dose ) )

( Appropriate Routes ) * Oral * Sublingual * Subcutaneous * Intravenous * Buccal * Epidural * Rectal * Intrathecal * Transdermal * Intraventricular * Intranasal

( Appropriate dosing interval ) * Short-acting opioid: : Oral q 4-64 6 h * Controlled-release release opioid: : Oral q 12/24 h * Fentanyl: Transdermal q 72 h * Short-acting opioid: : Subcutaneous q 3-43 4 h * Short-acting opioid: : Intravenous q 1-21 2 h

( Relative potency ratios ) Oral morphine to Ratio Rectal morphine 1 : 1 Subcutaneous morphine 1 : 2 Intravenous morphine 1 : 3 Subcutaneous diamorphine 1 1 : 3

(mg) Codeine IR q4~6h Codeine IR CR q12h Codeine Contin Tab 15,30 Purdue Frederick, Tab 100,150,200 (Canada) Oxycodone IR q4~6h Oxy IR Oxy Fast CR q12h Oxy contin Proladone Cap 5 5 Purdue Pharma L.P. Solution 20mg/ml (USA) Tab 10,20,40,80 Purdue Pharma L.P. (USA) Supp 30 Boots Company (Australia)

(mg) Morphine IR q4~6h MSIR Tab 5,10,20,30 Purdue Frederick, Supp 10,20,30 (Canada) Tab 10,20,30 NAPP Laboratories Ltd, (UK) Tab 15,30,60,100,200 Purdue Frederick, Supp 30,60,100,200 (Canada) Continus Tab 10,15,30,60,100,200 NAPP Laboratories Susp 20,30,60,100,200 Ltd,(UK) Cap 10,15,30,60,100,200 Rhone-Poulenc (Sprinklets)) Roper (Canada) /Kadian Cap 20,50,100 GlaxoWellcome (Pellets) (Australia) Cap 30,60,90,120, NAPPLaboratories 150, 200 Ltd. (UK) /Kadian Cap 20,50,100 (Pellets) GlaxoWellcome (Australia) Severedol CR q12h MS Contin MST Continus Meslon CR q24h MXL Kapanol /Kadian Kapanol /Kadian

(mg) Hydormorphone IR q4~6h Dilaudid Tab 2,4,8 Knoll Pharma Liq 1mg/ml (USA, Canada) Supp 3mg Amp 1,2,4 mg/ml/amp 10mg/ml (1, 5ml) Vials 2mg/ml (20ml) 10mg/ml(50ml) Powder 15-grain vial Palladone Cap 1.3, 2.6mg NAPP Lab. Ltd. Opidol Mundipharma CR q12h Hydromorph Contin Cap 3,6,12,24 Purdue Frederick Palladone Cap 2,4,8,16,24mg NAPP Lab. Ltd. Opidol Mundipharma

(mg) Fentanyl TD q3d Durogesic Patch: 25, 50, 75, 100 ug/h Janssen Pharmaceutica OTFC 2.5 5h Actiq ; Anesta Lollipop: 200, 400, 600, 800, 1200, 1600 ug Abbott Lab. Tramadol IR q4~6h CR q12h CR qd Tramal Tradonal Tramundin Tramtor Tramal Tramundin Muaction Tramundin Tab Grunenthal Cap Drops Supp Amp Cap ASTA Medica Drop 1 Supp Amp (Cap, drops, amp, supp) NAPP Lab. Amp: 100/2ml/amp Lotus Tab Grunenthal (Cap) Tab: 100 (Cap) NAPP Lab. Lotus NAPP Lab.

( Persistent pain ) ( Breakthrough pain ) 1 ( Around-the the-clock dosing ) 2 PRN ( as needed rescue supplements ) ) PRN

Oral PCA 0 12 24 MST PRN ( MSIR MST ) PRN ( MSIR ) MST

Transdermal Fentanyl day 1 day 2 day 3 TTS-F ( Breakthrough pain ) MSIR or Oral Transmucosal Fentanyl Citrate ( OTFC )

( Titrate ) 1 2 PRN 1 50 100% 2 25 50% 1 q 1 h 2 q 24 h

Adjuvants Antidepressants Corticosteroids Anticonvulsants Oral local anesthetics Antianxiety Biphosphonates Antihistamine CNS stimulants

( Side effects )

( Changing drug or Opioid rotation ), (Changing route) (Total pain)

New Formulations & Multiple Routes of Opioids Administration

(1) Opioids: (1) Controlled-release release (qd( / q12h ); Suspension / Pellets / Spinklets Codeine, Oxycodone, Morphine, Hydromorphone (2) Trandermal Fentanyl (3) Oral Transmucosal Fentanyl (4) Sublingual & Transdermal Buprenorphine (5) Tramadol NSAID s: (1) Potent NSAID: Ketorolac; (2) COX-2 2 inhibitors: Meloxicam, Celecoxib, Rofecoxib Valdecoxib, Parecoxib

(2) NMDA antagonists: (1) Ketanime (2) Dextromethorphan Bisphosphonates: (1) Clodronate ( Bonefos ) (2) Panidronate ( Aredia ) (3) Alendronate ( Fosamax ) Anticonvulsants: (1) Gabapentin ( Neurontin ) (2) Lamotrigine (3) Oxcarbazepine ( Trileptal ) Antidepressants: (1) Venlafaxine (2) Duloxetine Others: Stronium-89,.. etc.

(Anesthetic approaches) : (Sympathetic nerve block). (Trigger point injection). (Somatic blocks) ( ( local anesthetic blocks, neurolytic blocks). (Intraspinal infusion techniques) ( Epidural or intrathecal opioids with or without local anesthetics ).

An outline of the sympathetic nervous system & sympathetic blockade

Stellate ganglion block

Oral Ca 星狀神經結阻斷術 Stellate ganglion block WONG

Celiac plexus block

Splanchnic nerve block

Lumbar sympathetic block

Hypogastric plexus block

Supraorbital & Supratrochlear nerve block

Infraorbital & Mental nerve block

Maxillary & Mandibular nerve block Oral Ca NPC PHN

Gasserian ganglion block ( CT ) Trigeminal Neuralgia

Intercostal nerve block Ca with AHN Lung Ca with rib metastasis

Epidural Block ( Cervical, Thoracic, Lumbar ) PCEA

Trigger Point Injection Prostatic Ca Breast Ca NPC Gastric Ca, bone meta Pancreas Ca Colon Ca

Trigger Point Injection Gastric Ca Hepatoma

(Intraspinal opioid systems)

Neurostimulatory approaches (Non-invasive stimulatory approaches) : * (counter-irritation) * (TENS) (Invasive approaches) : * (Acupuncture) * (Percutaneous electrical nerve stimulation) * (Dorsal column (Spinal cord) stimulation) * (Deep brain stimulation)

Acupuncture Electro-acupuncture TENS Interferential therapy

Acupuncture Hepatoma Gastric Ca SSP

Spinal cord stimulation & Deep brain stimulation

Rehabilitation therapies : * To forestall or reduce the myofascial complication. (PT) * To identify methods that allow a p't to regain function without provoking painful episodes. (OT)

Surgical approaches : 1. Percutaneous cordotomy. 2. Surgical procedure for improving the underlying pathology : ie.. resection of neuroma. 3. Dorsal root entry zone lesion (DREZ). Psychological approaches : -- Congnitive therapies : Hypnosis & Distraction techniques...etc.

Neurosurgical procedures

Palliation for Cancer Pain 1. ( Palliative Surgery ): Gastrostomy, Tracheostomy,, Colostomy,..etc. 2. ( Palliative Chemotherapy ): Taxol, etc. 3. ( Palliative Radiotherapy ): Bone or brain metastasis, etc. 4. ( Palliative Nuclear Medicine ): -89 Stronium-89, etc.

Case: Male, 45 y/o Dx: Hepatoma with liver cirrhosis, T12T metastasis, cord compression and severe neuropathic pain Pre-op: op: Morphine 10mg 1# q4h, Trileptal 300mg 1# tid, Amitriphyline 25mg 1# hs, Celecoxib 100mg 1# bid Still severe pain with Pain score: 9-109

Op: Laminectomy T11-L1,, T12 T total corpectomy and removal of T12 tumor with bone cement and k-pins k reconstruction and post. U.S.S. instrumentation Post-op: op: PCA ( Morphine + Ketorolac + Haldol ) for 3 days Muaction ( Tramadol 100 mg ) 1# tid Celecoxib 1# bid Pain Score: 10 4

Alternative Therapies for Cancer Pain (1) ( Relaxation techniques ): (biofeedback) biofeedback) (hypnosis) ( Imagery / Visualization ) (Acupuncture) ( Acupressure ) ( Rehabilitation therapy ): ( physical and occupational ) (Recreational therapy): (Music and art therapy)

Alternative Therapies for Cancer Pain (2) ( Humor and laughter therapy ) ( Aromatherapy ) ( Spiritual and pastoral therapy ): ( spiritual care ) ) ( psychological counselling ) ( logotherapy ) ( life review ) ) ( religious counselling ). ( Chi-Gung Chi Chi-Kung )

Acupuncture Acupuncture ( Abdominal distension, Chest pain, Nausea / vomiting )

Aromatherapy

Rosemay Camdmile Clove Peppermint

(Lavender) (Lavender) (Forester) (Forester) (Rose) (Rose) (Lemon) (Lemon) (Jasmin Jasmin) (Mellafi Mellafi) (Sandal wood) (Sandal wood) (Pine needle) (Pine needle) (Sun flower) (Sun flower) (Maigold Maigold) (Lilies) (Lilies) (Violet) (Violet) (Sage) (Sage)

High-Tech Therapy

Bionic Transputer

WONG

486 486 200 53% 35% 1/3 58% NSAIDs 1/3 32% Tramadol Tramadol 42% MST MST 63% Multi-center study, n=486,

80.9% 65.2% 65.2% 26.4% 26.4% ( Transdermal Fentanyl ) 44.8% ( Trigger point injection ) ) 11.2% ( Patient-controlled Analgesia ) ) 8.8% ( Neural blockade ) 6.4% ( IM and IV of analgesics ):) 6.1% ( Physical therapy ) ) 2.7% ( Palliative radiotherapy ) ) 2.1% Stm study, n=330,, 2004

WHO: Reasons for Undertreatment of Cancer Pain 1. ( Lack of recognition by health care professionals ) 2. ( Lack of concern by government ) 3. ( Lack of availability of essential drugs ) 4. ( Fears concerning addiction among patients and the public ) 5. ( Lack of systematic education )

Barrier of Cancer Pain Management 46%.

The Median Scores of Cancer Pain Patients Concerns at Three Medical Centers in Taiwan Degree of Concern 5 4 3 2 1 4.7 4.0 ( n=383, TSGH, KVGH, NTUH ) Ger et al., J Pain Symptom Manage 2000; 20: 335-344 344 3.7 3.7 3.7 3.0 2.8 2.5 2.0

Identified Barriers to Cancer Pain Management by the Physicians ( n = 181 ) % 61 57 54 54 31 25 23 Ger et al., J Pain Symptom Manage 2000; 20: 335-344 344

( n = 605 ) Identified Barriers to Cancer Pain Management by the Nurses % 75.4 75.2 68.1 66.8 66.4 54.0 Ger et al., J Pain Symptom Manage 2000; 20: 335-344 344

Physician s s & Nurse s s Knowledge, Attitude & Behavior toward Morphine ( n=121 ) ( n=584 )

Good Pain Management 3333 (3-day Short-acting Drugs) (Upgrade to the 3 rd Ladder) (< 3 Breakthrough Pain/Day) (VAS < 3)

( Total Suffering ) ) (Total Pain) ( Total suffering ) ( Total care ) ( Pain ) ( Physical symptoms ) ( Psychological problems ) ( Social difficulties ) ( Spiritual concerns ) ( Cultural factors )

Successful cancer pain management Maximum patient comfort ( not just pain relief ) with minimum side effects.

! OK! We e do everything for our patient, but don t t add suffering!! OK

Thanks for your attention!