Systemic management

of pancreatic cancer:

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Palliative Care

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Sneana Bonjak
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@bosnjaksupport
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Institute for Oncology and Radiology of Serbia

Serbia, Belgrade
 Palliative care

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Interdisciplinary specialty, focused

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on preventing & relieving suffering,

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and supporting the best possible

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QoL for patients and their families
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Early refferal & initiation of PC for
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all patients with advanced /

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metastatic pancreatic cancer

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Ferrell BR, et al. JCO 2017 35:1, 96-112

 Pain management

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Remove

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Treating / removing the cause of pain

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Relieve

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o Analgesics & co-analgesics

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o Non-drug treatments (celiac plexus
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neurolysis)
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o Interdisciplinary approach: total pain

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Ripamonti CI., et al. Ann Oncol 2012; 23 (Suppl 7): vii39-vii154

ESMO Gudelines
7-10

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OPIOID

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4-6 NSAIDs

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Paracetamol

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OPIOID

1-3 EE
NSAIDs
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Paracetamol
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Paracetamol
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NSAIDs
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Co-analgesics
Medications to prevent & treat adverse effects
 Opioids

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Pain intensity

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Step 2 WHO (weak) & Step 3 WHO (strong) opioids

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Pharmacodynamic profile

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Full agonist

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Partial agonist

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Mixed agonist/antagonist (not recommended)
Antagonists
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Opoids with non-opioid mechanism of action
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Pharmacokinetic profile
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Short acting opioids: IR & MR formulations

Long acting opioids
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Inactive vs. active metabolites

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The route of administration:

Oral, transdermal, parenteral, transmucosal, etc.
 The Usefulness of Weak Opioids

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Codeine (or tramadol) compared with low

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dose morphine (Mo: 5 mg, Q4h) for moderate

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pain (4-6/10)

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Morphine:

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Significantly higher clinically meaningful (30%)
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and highly meaningful (50%) pain relief
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Earlier onset of analgesic effect and less need for
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rotation
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Comparable good tolerability

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Bandieri E, et al. JCO 2016 34:5, 436-442

 Strong opioids

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Morphine: a reference strong opioid

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Oral first-line opioids: morphine,

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oxycodone, hydromorphone

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TD alternatives to oral opioids (Fen, Bu)

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Methadone: a first, second-line, or an
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adjuvant opioid w/ unique pharmacology
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& safety concerns

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Tapentadol: opioid & non-opioid (SNRI)

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Caraceni A, et al. Lancet Oncol 2012

Corly O et al. Annals Oncol, 2016
 Route of administration

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The least invasive route is preferred:

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Oral (IR, MR) or trasdermal (stable pain)

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Parenteral: SC, IV

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Transmucosal: SL, buccal, nasal, rectal
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Intraspinal delivery
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Morphine mouthwash (oral mucositis)

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Intramuscular: NOT recommended

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 Regular analgesia

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Oral opioids

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Short-acting: IR morphine, oxycodone,

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hydromorphone

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Dose every t : Q4h, adjust dose Q24h

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Long-acting: MR morphine, hydromorphone,
oxycodone EE
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Dose Q8h, Q12h, Q24H, adjust dose Q 2-4 days
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Transdermal opioids
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Long acting fentanyl: dose every 72h

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Long acting buprenorphine: dose every 3, 4, 7 days

 Rescue treatment

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Use the same opioid (? methadone and TD

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fentanyl)

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Use only IR formulations

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Rescue dose: 10% (5-20%) of the regular

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opioid dose /24h
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Rescue timing for morphine: every tCmax
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PO q 1 h, 3 consecutive doses
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SC q 30 min
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IV q 1015 min
 Individual dose titration

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The same starting dose: equivalent to 20-30

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mg of PO morphine / 24h (opioid-naive

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patients, with no renal comorbities)

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Driven by safety, not by the intensity of pain

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Gradual escalation of the starting dose,
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until pain relieved or unmanageable
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adverse effects
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The minimal clinically meaningful increase:

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30-50% /total 24 h dose

Bruera E, Paice JA. Cancer pain management, 2015 ASCO Educational Book
 ss
There is no single opioid of

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choice for all patients, but

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one opioid can be optimal

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for an individual patientEE
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S. Mercadante, E. Bruera / Critical Reviews in Oncology/Hematology 99 (2016) 241248

 Individual tailoring

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Favorable balance btw analgesia and AEs

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Renal failure (GFR < 30 mL/min): fentanyl,

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buprenorphine, methadone

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Liver failure (morphine, hydromorphone)

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Alcohol / drug abuse: methadone, buprenorphine
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Coexisting symptoms: dyspnea, nausea,
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vomiting, constipation
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Methadone superior to TD Fen for cancer pain

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with neuropathic component?

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Caraceni A, et al. Lancet Oncol 2012

Bruera E et al. J Clin Oncol 2004
Haumann J et al. Eur J Cancer 2016
 Transdermal opioids

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Fentanyl, buprenorphine

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Skin patch: LA formulation of Fen / Bu

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Higher level of evidence supports the use

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of TD Fen in cancer pain
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TD Fen: less constipation, nausea &
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urinary retention vs morphine
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Dysfagia, prominent GI Sx (nausea,

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vomiting, constipation, MBO), renal failure

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Cave!: Cachexic, febrile patients

Caraceni A, et al. Lancet Oncol , Volume 13 , Issue 2 , e58 - e68
 Methadone versus Morphine As a

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First-Line Strong Opioid for Cancer

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Pain: a randomized double-blind

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study

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Bruera E, Palmer JL, S. Bosnjak, et al.
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J Clin Oncol 2004, 22:185-192

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 Methadone: a unique opioid

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Efficacy similar to morphine (Cochrane, 2017)

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Opioid & NMDA antagonist

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High oral bioavailability, long T1/2, long

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duration of action (8-12h)

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Only LA opioid available in a liquid form
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Among the opioids of choice in pts with:
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renal insufficiency;
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risk for opioid use disorder

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Roger C, et al. APS guidelines. The Journal of Pain 2014; 15:321-337

 Methadone Safety Guidelines

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Baseline QTc interval > 500 ms: avoid!

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First-line use: 2.5 mg tid Q8h, dose increase: 5

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mg/24h (not earlier than after 5-7 days)

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Second-line use: Mo: Met dose ratio 5:1, max initial

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Met dose 30 mg/24h
Do not use Me for BTP or PRN
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Close monitoring for sedation, respiratory
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depression, arrhythmia
Conc meds w/ potential interactions / additive AEs
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Assess for AEs within 3-5 days after initiating /

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increasing the dose of methadone

Roger C, et al. APS guidelines. The Journal of Pain 2014; 15:321-

337
 Undesirable effects of opioids
(PCF5)

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Common initial Less common

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Nausea & vomiting Neurotoxicity

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Drowsiness Hyperalgesia /allodynia

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Lightheadedness/unsteadiness Myoclonus
Delirium Cognitive failure/delirium

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hallucinations

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Common ongoing Sweating
Constipation Urinary retention
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Nausea & vomiting Postural hypotension
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Dry mouth Spasm of the sphincter of Oddi

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Pruritus
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Possible ongoing
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Suppression of hypothalamic- Rare

pituitary axis / immune system Respiratory depression
Psychological dependence
 Opioids: adverse effects

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Prevent:

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Individual dose titration

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Laxatives, metoclopramide

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Treat:
Reduce the dose EE
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Medication for Tx of adverse effects

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Switching to another opioid / administration

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route

Cherny N et al. JCO 2001

 Opioid switching

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Replacing one strong opioid to which a

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patient is poorly responsive with another one

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To improve pain relief, tolerability or both

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Knowledge of equivalent doses & strict

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monitoring
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Reduce the dose gathered from equivalent
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tables by 30-50%
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No fixed potency ratio btw Met and Mo

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Mercadante S, Bruera E. Critical Reviews in Oncology/Hematology 2016

 Tumor induced neuropathic pain

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Disease-directed treatments

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Analgesics (opioids)

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Coanalgesics

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Universal: corticosteroids
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Analgesic antidepressants & anticonvulsants

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Carla RI, et al. ESMO CPG. Ann Oncol 2012; 23 (Suppl 7): vii39-vii154
NeuPSIG IASP guidelines 2016
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Total Pain Concept

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http://www.iasp-pain.org/
 Nausea and vomiting: advanced cancer

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Metabolic: hypercalcemia, hyponatremia, uremia

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Medications (opioids, NSAILs, antibiotics)

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Microbes: infection

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Mental anxiety

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Motility (gastric stasis, constipation)
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Mechanical: malignant gastric / bowel obstruction)
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Metastases: brain, meningeal or brain tumor

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Movement: vestibular dysfunction

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Myocardial
MASCC/ESMO 2016
 MASCC / ESMO
recommendations

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 MASCC / ESMO recommendations

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Bowel obstruction:

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Octreotide + an antiemetic (haloperidol preffered)

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Anti-cholinergic antisecretory agents (e.g., scopolamine

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butylbromide, glycopyrronium bromide) and/or

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corticosteroids (adjunct or an alternative)

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Nausea and vomiting of unknown cause: metoclopramide
Metoclopramide (w/ caution in partial bowel obstruction
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contraindicated in complete bowel obstruction)
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Alternatives: haloperidol, olanzapine, levomepromazine)

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Walsh D, et al., Support Care Cancer 2017; 25: 333-340

 Anorexia / cachexia syndrome

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Loss of appetite and/or an aversion to

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food, decreased food intake

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Loss of lean body mass & body weight

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Fatigue, weakness
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Increased protein breakdown
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Poor prognosis and worse survival

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http://www.cancernetwork.com/cancer-management/anorexia-and-cachexia
 Cancer Cachexia International
Consensus Definition

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Multifactorial syndrome defined by an

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ongoing loss of skeletal muscle mass

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(with or without fat mass) that cannot be

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fully reversed by conventional nutritional
support and leads to progressive
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functional impairment.
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Fearon K, et al. Lancet Oncol 12:485-495, 2011

 Clinical Practice Guidelines on
Cancer Cachexia

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Consensus Recommendations

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Enteral nutrition YES

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Parenteral nutrition No

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Multimodal therapy Yes (being studied in MENAC trial)

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(nutrition, physical training, medications)

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Megestrol acetate Stimulate appetite + increase weight, but
not muscle
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Steroids Yes (short term) w/ additional benefit on

other Sx
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Anticancer Tx Can be beneficial or detrimental

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Prokinetics: metoclopramide Yes, for nausea, early satiety

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European Palliative Care Research Collaborative, 2011

 CONCLUSION

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Treat cancer patient

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while treating

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patients cancer
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