Symptom control in the terminally ill lung cancer patient

1. Symptom control in the terminally ill lung cancer patient Ülkü Yılmaz Turay Associated Prof, MD Atatürk Chest Disease and Surgery Education and Training Hospital

2. ‘One of the worse aspects of cancer pain is that it is a constant reminder of the disease and of death… My dream is for a medication that can relieve my pain while leaving me alert and with no side effect Jeanne Stover Clinical Practice Guideline Management of Cancer Pain 1991-1992

3. Presentation plan • Definitions; terminally ill patient, palliative, supportive, end of life care, • Symptoms in terminally ill lung cancer patient and management of these symptoms, • Where should terminally ill lung cancer patient look after.

4. Symptoms ın lung cancer • Primary cancer ıtself • Locoregional metastases within the thorax • Extrathoracic metastases • Paraneoplastic syndromes • Constitutional symptoms • Cough • Dyspnea • Hemoptysis • Pain • Recurrent nerve palsy • Phrenic nerve palsy • Superior sulcus tumor • Horner syndrome • Pain (Thorax, pleura) • VCSS • Pericardial involvement • Eusophageal involvement • Paraneoplastic smyyndromes • HOA • Neurological, oplastic syndromes • Pain(bone metastasis • Liver metastasis • Intraabdominal lymph nodes • Brain, spinal cord metastases • Exrtrathoracic lymph node involvement • Skin metastases • Fatigue, anorexia/cachexia • Anxiety, depression

5. Definition of terminally ill patient • Year to months • Months to week • Weeks to days Last year of life: • Performance status; ECOG>3, KPS<50 • Hypercalcemia • Central nervous system metastases • Delirium • Superior vena cava syndrome • Spinal cord compression • Cachexia • Malignant effusions • Liver failure • Kidney failure • Other serious comorbid conditions www.nccn.org

6. Definition of terminally ill patient • Akciğer kanserli olgularda son dönem; ölümden önceki 8 hafta olarak • alınmıştır.

7. Symptoms in the terminal stage of lung cancer Chest 2007 131: 394-397

8. Palliative care-Supportive care • Palliative care is an approach that improves the quality of life of patients and their families facing the problem associated with life-threatening illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial and spiritual. Supportive care Palliative care End of life WHO 2002

9. Palliative care Palliative care Curative treatment Curative treatment Palliative care Palliative care Palliative care Curative treatment Death Am J Respir Crit Care Med 2008;177: 912-927

10. Palliative chemotherapy • Nearly half of the patients had received chemotherapy in the last month of life, • One patients out of five received treatment in the last two weeks. Oncologist 2006:11;1095-9

11. Skor Skor Eur J Cancer 2009

12. Symptom management of terminally ill cancer patients complicated by several factors • Older age • Malnutrition, low albumin • Frequent autonomic failure • Decreased renal function • Borderline cognition • Lower seizure treshold(brain involvement, opioids) • Long-term opioid therapy • Multiple drug therapy

13. Symptom assessment How do we measure? • Symptom assessment scale Why do we need to measure? • Able to compare • To find all symptomps • Quality assurance/advocacy • Association between symptom severity and survival Cancer 2010;116:137-45

14. Symptom assessmentEdmonton Symptom Assessment Scale

15. Quality of life assessment EORTC QLQ-LC 30 Lung cancer symptom scale(LCSS) QOL Yaşam Kalitesi J Clin Oncol 2007;25:5381-5389

16. QOL

17. QOL

18. Patient suffering from pain,what should we do? 1- Assessment of pain • History, • Validated assessment tool, • Physical examination including neurological

19. Patient suffering from pain,what should we do? 2- Diagnose the pain • Origin; primary disease, treatment, other • Pain due to progression of disease • Post-chemotherapy pain • Post-radiotherapy pain • Post-operative thoracic pain • Type of pain • Mecanism of pain • Different dimensions of pain experience and other symptoms Lung cancer 2010;68:10-15

20. Patient suffering from pain; • Types of pain Nociceptive pain • Somatic pain ( parietal pleura) • Visceral pain (mechanoreceptive ischemic stimulus)

21. Patient suffering from pain; • Neuropathic pain • Radiculopathy • Mononeuropathy • Peripheral neuropathy • Plexopathy • Postherpetic neuralgia • Malignant brachial pleksopathy

22. Assessment of pain intensity • Visual analog scale • Numeric scale • Categorical scale No pain Worst possible No pain 1 2 3 4 5 6 7 8 9 10 Worst possible No Weak Moderate Severe Very severe Extreme pain pain pain pain pain pain

23. Symptomatic pain treatments By the ladder By the mouth By the clock

24. WHO Analgezic ladder Step 3 Reference: Oral morphine Hydromorphine Methadone Phentanyl +/- non-opioids +/- Adjuvants Step 2 Codeine, Tramadol +/- non-opioids +/- Adjuvants Step 1 Non opioid: Paracetamol AINS +/- Adjuvants

25. Pain treatment: The use of opioids • OPIOIDS • Morphine 10 • Hydromorphon 2 • Oxycodon 6 • Phentanyl 0.1 • Methadone (değişken) • MORPHINE • Bioavailability %15-65 • Oral dose = 3 x IV, IM dose • Plasma halflife: 3 h

26. Opioid titration • Add 30 % of total dose • Total dose+breakthrough pain Four hour dose = 6

27. Pain treatment: In patients who can’t take oral medications • Transdermal preperations; Phentanyl • Effective dose determined by a short acting opioid • Not a first choice • Swallowing difficulties, alteration of drug absorbtion or other intolerances to the oral route • Stable pain • Conversion from Morphine to phentanyl; No clear protocols have been established 1:70-100 • Subcutan route; except methadone most drug used by subcutaneous infusion. Safe and effective for teminally ill patients. • Rectal route

28. Treatment of breakthrough pain • 90 % BTP can be controlled with oral/sc route. • Transmucosal, oral, nasal phentanyl: failure of oral/sc Available inTurkey: oral transmucosal phentanyl

29. Side effects of opioids • Sedation • Respiratory depression • Nausea-womiting • Constipation • Urinary retention • Pruritus • Hydrosis • Cognitive impairment and neurotoxicity • Tactile and visual hallucinations • Generalized myoclonus • Hyperalgezia • Allodynia

30. Management of opioid side effects • Constipation Preventive measures: • Stimulant laxative+stool softener ; senna, docusate 2 tb her sabah; 8-12 tb/gün • Maintain adequate fluid intake • Maintain adequate dietary fiber intake If constipation develops; • Magnesiumum hydrokside 30-60 ml/day • Bisakodyl • Rectal supp • Lactulose • Sorbitol • Neurological side effects • Consider changing the opioid • Decrease dose of opioid • Hydration • Eliminate other phsycothropic drugs

31. Adjuvants • Antidepressants: Amitriptyline • Anticovulsants: Carbamazepine, phenytoin,, valproate, clonazepam • Gabapentin, pregabalin • Corticosteroids:dexamethasone • NMDA (N-metyl D-aspartat)Antagonists; Ketamine

32. Interventional procedures • Spinal route (Epidural, intrathecal) Opioid; morphine Lokal anesthetics; bupivakaine, ropuvakaine Klonidin • Percutaneous cordotomy

33. Non-pharmacological approaches • Psychological • Anxiety • Depression • Insomnia • Physical • Cognitive, behavioral approaches

34. Palliation of brain metastases Brain metastases; • NSCLC % 35 • SCLC % 50 TREATMENT: Whole-brain radiation therapy Corticosteroids

35. Dyspnea directly caused by cancer Pulmonary parenchyma involvement(primary, methastatic) Intrinsic or extrinsic airway obstruction by tumor Lymphangitic carcinomatosis Pleural effusion Pericardial effusion VCSS Tumoral embolism Phrenic nerve palsy Atelectasis Trachea-eusophageal fistula Chest wall involvement Dyspnea indirectly caused by cancer Pneumonia Cachexia Anemia Electrolit disturbances Pulmonary emboli Paraneoplastic syndromes Ascide Respiratory muscle dysfunction Pain Pneumothorax Caused by cancer therapy Surgery Radiation pneumonitis Chemotherapy induced pulmonary fibrosis/ pneumonia Causes of dyspnea in lung cancer patients

36. Symptomatic treatment of dyspnea • Oxygen • Pharmacologic therapy • General supportive measures

37. Symptomatic treatment of dyspnea: Oxygen • In patients who are hypoxemic at rest on room air; decreased dyspnea • In patient who are nonhypoxemic; • Placebo ? • Trigeminal nerve(V2 branch) stimulation ?

38. Symptomatic treatment of dyspnea: Pharmacologic therapy Mechanism of action opioids in pharmacological management of dyspnea; • Reduce the central processing of neural signals within the CNS • Reduce oxygen consumptin in exercise and rest • Reduce perception of dyspnea • Pulmonary vasodilatation • Relieve dyspnea by depressing hypoxic or hypercapnic ventilatory response Support Care Cancer 2008; 16: 329-37 Nat Clin Pract Oncol 2008;2: 90-100

39. Symptomatic treatment of dyspnea: Opioids • The optimal type, dose and mode of administration of opioids have not yet been determined. • Opioid treatment in dyspneic patients; • Start low dose and titrate • Opioid history of patient Opioid –naive patint: • 5 mg Morphine sulphat; subcutaneus. • Increase hourly • For patients receiving opioids, 25 % increase in baseline dose may provide relief for several hours .

40. Pharmacologic Nebulised opioids Nebulised furosemid Corticosteroids Bronchodilators General supportive care Fan Pulmonary rehabilitation Symptomatic treatment of dyspnea

41. Symptomatic treatment of dyspnea • Benzodiazepines Lorazepam 0.5-1 mg oral Diazepam 5-10 mg oral Clonazepam 0.25-2 mg oral • Phenothiazines Clorpromasine 7.5-25 mg oral-sc Metotrimeprasin 2.5-10 mg oral-sc Levomepromazine 6.25 oral Cancer Treat Rev 1998; 24:69 Nat Clin Pract Oncol 2008;2:90-100

42. Non-productive cough Codeine 10-20 mg X 4-6 Dekstrometorphan 10-20 mg X 3-6 Benzonatate Levodropropisine75 mg X 3 Dihydrocodeine 10 mg X3 Productive cough Hydration Physiotherapy Air humidification Acetylcysteine Cough • Bronchodilators • Corticosteroids • Nebulised lidocaine • Nebulised morphine • Nebulised phentanyl

43. Fatigue Fatigue Correction of potential etiologies Fluid- Electrolytes Sleep disorders Depression Deconditioning Anemia Symptomatic therapies Nonpharmacologic therapy; Support group, education Pharmacologic therapy Psychostimulants Clin Lung Cancer 2006;4:241-249

44. Pharmacological therapy of fatigue • Methylphenidate • Modafinil • Dexmethylphenidate • Dextroamphetamine • Corticosteroiss • Megestrol acetate • Donepezil ? www.nccn.org J Natl Cancer Inst 2008;100:1155

45. Anoxia/Cachexia The cancer –related anorexia/cachexia syndrome is characterized by anorexia and loss of body weight associated with reduced muscle mass and adipose tissue . In terminally ill patient; • Treatment goals of the treatment are symptomatic rather than nutritional. • Social aspects of eating over the nutritional benefit. • Corticosteroids are capable of improving appetite, nausea and energy for brief periods of time. • Megestrol acetate ??

46. Hydration Artificial hydration when patients develop reduced oral intake because of profound anorexia, dysphagia or severe nausea and vomiting; • Dehydration and electrolyte imbalance can cause confusion, restlessness, neuromuscular irritability, • Improve comfort and life quality, • Lead to clear the toxic drug metabolites, • Parenteral hydration is minimum standart of care, continuing this treatment bond to life • To cause to cease thirst recommended. J Clin Oncol 2005;23:2366-71

47. Hydration Volumes of 1000-1500 cc/day are usually enough to maintain normal urine out put ; • Decreased insensible water losses as a consequence of reduced physical activity, • Decreased absolute water requirements • Decreased clearance of free water because of an increase of ADH due to nausea and womiting • Methods of fluid administration: • Intravenous • Subcutaneus; hypodermoclysis • Proctolysis J Clin Oncol 2005;23:2366-71

48. Depression • Depression is the most common mental health problem encountered in palliative medicine Treatment: Relieve uncontrolled symptoms Supportive psychotherapy Pharmacologic therapy NCCN Guideline-2009

49. Delirium Delirium is the most common neuropsychiatric complication in patints with advanced cancer; • Fluctuating levels of conciousness • Changes in the sleep/wake cycle • Psychomotor agitation • Hallucinations • Delusions • Perception abnormalities

50. Predisposing factors: Opioid-induced neurotoxicity Brain metastases Cancer treatment Psychotropic drugs (Tricyclic antidepressants, benzodiazepines) Metabolic (increased calcium, decreased sodium, renal failure) Paraneoplastic syndromes Sepsis Treatment Treatment of predisposing factors Delirium Haloperidol Clorpromasine, olanzepine,risperidon Midazolam Propofol JAMA2008;300:2898-910