Pancreatic cancer Palliative Care
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1 Pancreatic cancer Palliative Care Snežana Bošnjak Institute for Oncology and Radiology of Serbia Dept. Supportive Oncology & Pall Care Serbia, Belgrade
2 Pancreatic Cancer: Palliative Care Abdominal / epigastric pain (ESMO, 2012) Nausea and vomiting in advanced cancer (MASCC / ESMO, 2016) Anorexia & cachexia syndrome Malnutrition (ESPEN, 2016) Depression (ESMO, 2018) and anxiety Biliary tract obstruction: endoscopic stent placement Ascites Venous thromboembolism (ESMO, 2011) Metastatic Pancreatic Cancer ASCO guideline 2016, 2018
3 Patient-centered pain treatment Routine screening for pain (ESAS) Remove the cause of pain: Treat the treatable Celiac Plexus Neurolysis; palliative CT / RT Releive pain Physical & non-physical PharmacoTx & non-pharmacological interventions Multidisciplinary approach & team work Personalized definition of success Dalal S, Hui D, Nguyen L, et al:. Cancer 2012; 118: Hui D, Bruera E. J Clin Oncol 2014; 32: Metastatic Pancreatic Cancer ASCO guideline 2016, 2018
4 ESMO Gudelines OPIOID ± NSAIDs Paracetamol 1-3 OPIOID ± NSAIDs Paracetamol Paracetamol NSAIDs Co-analgesics (NeP, bone pain, visceral pain) Medications to prevent & treat adverse effects
5 The Usefulness of Weak Opioids Codeine (or tramadol) compared with low dose morphine (Mo: 5 mg, Q4h) for moderate pain (4-6/10) Morphine: Significantly higher clinically meaningful ( 30%) and highly meaningful ( 50%) pain relief Earlier onset of analgesic effect and less need for rotation Comparable good tolerability Bandieri E, et al. Journal of Clinical Oncology :5,
6 Strong opioids Oral first-line opioids: morphine, oxycodone, hydromorphone TD alternatives to oral opioids (Fen, Bu) Methadone: an alternative strong opioid with non-opioid mechanism of action Tapentadol: opioid & non-opioid (SNRI) Caraceni A, et al. EAPC guidelines. Lancet Oncol 2012; 13: e58 68 Ripamonti CI. ESMO guidelines: cancer pain. Ann Oncol 2012; 23 (Suppl 7): vii39-vii154. Corli O, et al. Annals Oncol 2016; 27:11 Meracadante S, Bruera E. JPSM 2018;55:
7 Opioids: routes of administration The least invasive route is preferred: Oral (IR, MR) or transdermal (stable pain) Parenteral: SC, IV Transmucosal: SL, buccal, nasal, rectal Intraspinal delivery Morphine mouthwash (oral mucositis) Intramuscular: NOT recommended Caraceni A, et al. EAPC guidelines. Lancet Oncol 2012; 13: e58 68 Ripamonti CI. ESMO guidelines: cancer pain. Ann Oncol 2012; 23 (Suppl 7): vii39-vii15
8 Opioids: individual dose titration The starting dose of an opioid: Driven by safety, not by the intensity of pain Equivalent to mg of PO morphine / 24h (opioid-naive patients, with no renal comorbities) Dose titration: gradual escalation of the starting dose, until pain is relieved or unmanageable adverse effects occur The minimal clinically meaningful increase: 30-50% /total 24 h dose Caraceni A, et al. EAPC guidelines. Lancet Oncol 2012; 13: e58 68 Ripamonti CI. ESMO guidelines: cancer pain. Ann Oncol 2012; 23 (Suppl 7): vii39-vii15
9 Opioid dosing Chronic, persistent pain: Regular by the clock analgesia w/ short-acting (IR) or long acting (MR) oral formulations Rescue doses ( as needed ): for pain that is uncontrolled w/ regular regimen Preventive dosing: for incident BTP Caraceni A, et al. EAPC guidelines. Lancet Oncol 2012; 13: e58 68 Ripamonti CI. ESMO guidelines: cancer pain. Ann Oncol 2012; 23 (Suppl 7): vii39-vii15
10 Regular Dosing First-line oral opioids Morphine, Oxycodone, Hydromorphone, Dose once every half life PO 4 hr for IR formulations Steady state after 5 half-lives Continue Tx with MR formulations (Q8h; Q12h; Q24h) for better compliance EPEC-O curriculum
11 Rescue doses Use the same opioid (methadone and TD fentanyl may be exceptions) Use only IR formulations (PO, SC, IV) Offer 10% (5-20%) of the regular opioid dose / 24h Repeat at every Time to Cmax 1 h for IR oral opioids EPEC-O curriculum
12 Breakthrough (episodic) pain Predictable (incident) Timing a painful activity after regular or preventive dose (1 2h after an oral opioid) Unpredictable (spontaneous): Rapid onset/ fast offset of analgesia is needed IR formulations of oral opioids Transmucosal fentanyl formulations Morphine i.v as an alternative if available Caraceni A, et al. EAPC guidelines. Lancet Oncol 2012; 13: e58 68 Ripamonti CI. ESMO guidelines: cancer pain. Ann Oncol 2012; 23 (Suppl 7): vii39-vii15
13 Opioids: individual tailoring Favorable balance btw analgesia and AEs Renal failure (GFR < 30 ml/min): fentanyl, buprenorphine, methadone Liver failure (morphine, hydromorphone) Alcohol / drug abuse: methadone, buprenorphine Coexisting symptoms: nausea, vomiting, bowel obstruction, constipation, dyspnea Methadone superior to TD fentanyl for cancer pain with neuropathic component Caraceni A, et al. EAPC guidelines. Lancet Oncol 2012; 13: e58 68 Ripamonti CI. ESMO guidelines: cancer pain. Ann Oncol 2012; 23 (Suppl 7): vii39-vii15 Haumann J et al. Eur J Cancer 2016
14 Prevent: Opioids: adverse effects Individual tailoring / dose titration Laxatives, antiemetics New formulations (oxycodone + naloxon) Treat: Reduce the dose, if the pain is stable Medications for Tx of adverse effects Switching to another opioid / administration route Cherny N, et al. J Clin Oncol 2001;19: S. Mercadante, E. Bruera. Critical Reviews in Oncology / Hematology 99 (2016)
15 Pancreatic cancer: neuropathic pain Celiac Plexus Block & CP Neurolysis Analgesics (opioids:? methadone) Coanalgesics Corticosteroids (for decompression) Analgesic atidepressants & anticonvulsants Ripamonti CI. ESMO guidelines: cancer pain. Ann Oncol 2012; 23 (Suppl 7): vii39-vii15 NeuPSIG IASP guidelines 2016
16 Adjuvant analgesics for neuropathic pain Analgesic anticonvulsants : Pregabalin Gabapentin Analgesic antidepressants The tricyclics (nortriptyline) SNRIs (duloxetine) Adjuvant analgesics for CIPN: Duloxetine
17 Total Pain Concept Saunders S. BMJ 1996;313:1599/1601
18 Nausea and vomiting in advanced cancer ecommendations
19 Nausea and vomiting: advanced cancer Tumors of the GI tract and thorax Metabolic & toxic o Hypercalcemia, hyponatremia, liver, renal failure o Medications (opioids, NSAILs, SSRIs, antibiotics, oral iron ) o Infection & inflammation in the GI tract Motility & mechanical disorders in the GI tract o o Gastric outlet / duodenal, bowel obstruction Gastroparesis, hepatomegaly, ascites, constipation CNS causes o Increased IC pressure, meningeal infiltration, vestibular Behavioral: anxiety, depression Roila F. et al., Annals of Oncology 2016; 27 (Supplement 5): v119 v133 Walsh D, et al. Support Care Cancer 2017; 25: Navari RM. Oncology (Williston Park) 2018; 32(3):121-5, 131, 13
20 Nausea and vomiting-advanced cancer MASCC / ESMO recommendations Bowel obstruction (BO) Gastric outlet / duodenal: Endoscopic duodenal stenting Octreotide + an antiemetic (haloperidol preferred) Corticosteroids for decompression Advanced cancer-unspecified cause: Metoclopramide is the drug of choice Haloperidol, levomepromazine, olanzapin: alternatives Opioid-induced nausea and vomiting: no Rec can be made Walsh D, et al., Support Care Cancer 2017; 25:
21 Anorexia / cachexia syndrome Metabolic syndrome Loss of appetite and / or an aversion to food, decreased food intake Loss of lean body mass & body weight Fatigue, decreased physical function Compromised QoL Suboptimal treatment outcomes, decreased survival Hui D. J Oncol Pract 2016: 12: Fearon K, et al. Lancet Oncol 12: , 2011
22 Cancer Cachexia International Consensus Definition Multifactorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. Fearon K, et al. Lancet Oncol 12: , 2011
23 Bruggeman AR, et al. J Oncol Pract 2016; 12:
24 Clinical Practice Guidelines: Cancer Cachexia Consensus Recommendations Nutrition Impact Symptoms Megestrol acetate Steroids Prokinetics: metoclopramide Oral or enteral nutrition Parenteral nutrition Anticancer treatment Treat the treatable : delayed gastric emptying /gastroparesis, constipation, ascites, depression Stimulate appetite + increase weight, but not muscle (VTE risk!) Yes (short term) w/ additional benefit on other Sx Nausea, vomiting, early satiety YES NO Beneficial or detrimental European Palliative Care Research Collaborative, 2011
25 FIG 3. Multimodal approach to cancer cachexia. Published in: Andrew R. Bruggeman; Arif H. Kamal; Thomas W. LeBlanc; Joseph D. Ma; Vickie E. Baracos; Eric J. Roeland; JOP 2016, 12, DOI: /JOP Copyright 2016 American Society of Clinical Oncology
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27 Cancer Related Fatigue Dexametahsone 4 mg BID better than placebo for cancer fatigue at day 8 and Yennurajalingam S, Frisbee-Hume S, Palmer JL, et al.j Clin Oncol. 2013; 31:
28 CONCLUSION See and treat cancer patient while treating patient s cancer
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