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Symptom control in the terminally ill lung cancer patient. Ülkü Yılmaz Turay Associated Prof, MD Atatürk Chest Disease and Surgery Education and Training Hospital. ‘One of the worse aspects of cancer pain is that it is a constant

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symptom control in the terminally ill lung cancer patient

Symptom control in the terminally ill lung cancer patient

Ülkü Yılmaz Turay Associated Prof, MD

Atatürk Chest Disease and Surgery Education and Training Hospital


‘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

presentation plan
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.
symptoms n lung cancer
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
definition of terminally ill patient
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

definition of terminally ill patient1
Definition of terminally ill patient
  • Akciğer kanserli olgularda son dönem; ölümden önceki 8 hafta olarak
  • alınmıştır.
palliative care supportive care
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

palliative care
Palliative care

Palliative care

Curative treatment

Curative treatment

Palliative care

Palliative care

Palliative care

Curative treatment


Am J Respir Crit Care Med 2008;177: 912-927

palliative chemotherapy
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



Eur J Cancer 2009

symptom management of terminally ill cancer patients complicated by several factors
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
symptom assessment
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

ya am kalitesi
Quality of life assessment


Lung cancer symptom scale(LCSS)


Yaşam Kalitesi

J Clin Oncol 2007;25:5381-5389

patient suffering from pain what should we do
Patient suffering from pain,what should we do?

1- Assessment of pain

  • History,
  • Validated assessment tool,
  • Physical examination including neurological
patient suffering from pain what should we do1
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

patient suffering from pain
Patient suffering from pain;
  • Types of pain

Nociceptive pain

    • Somatic pain ( parietal pleura)
    • Visceral pain (mechanoreceptive ischemic stimulus)
patient suffering from pain1
Patient suffering from pain;
  • Neuropathic pain
    • Radiculopathy
    • Mononeuropathy
    • Peripheral neuropathy
    • Plexopathy
    • Postherpetic neuralgia
    • Malignant brachial pleksopathy
assessment of pain intensity
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

symptomatic pain treatments
Symptomatic pain treatments

By the ladder

By the mouth

By the clock

who analgezic ladder
WHO Analgezic ladder

Step 3

Reference: Oral morphine




+/- non-opioids

+/- Adjuvants

Step 2

Codeine, Tramadol

+/- non-opioids

+/- Adjuvants

Step 1

Non opioid:



+/- Adjuvants

pain treatment the use of opioids
Pain treatment: The use of opioids
    • Morphine 10
    • Hydromorphon 2
    • Oxycodon 6
    • Phentanyl 0.1
    • Methadone (değişken)
    • Bioavailability %15-65
    • Oral dose = 3 x IV, IM dose
    • Plasma halflife: 3 h
opioid titration
Opioid titration
  • Add 30 % of total dose
  • Total dose+breakthrough pain

Four hour dose



pain treatment in patients who can t take oral medications
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
treatment of breakthrough pain
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

side effects of opioids
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
management of opioid side effects
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
  • Antidepressants: Amitriptyline
  • Anticovulsants: Carbamazepine, phenytoin,, valproate, clonazepam
  • Gabapentin, pregabalin
  • Corticosteroids:dexamethasone
  • NMDA (N-metyl D-aspartat)Antagonists; Ketamine
interventional procedures
Interventional procedures
  • Spinal route (Epidural, intrathecal)

Opioid; morphine

Lokal anesthetics; bupivakaine, ropuvakaine


  • Percutaneous cordotomy
non pharmacological approaches
Non-pharmacological approaches
  • Psychological
    • Anxiety
    • Depression
    • Insomnia
  • Physical
  • Cognitive, behavioral approaches
palliation of brain metastases
Palliation of brain metastases

Brain metastases;

  • NSCLC % 35
  • SCLC % 50

TREATMENT: Whole-brain radiation therapy


causes of dyspnea in lung cancer patients
Dyspnea directly caused by cancer

Pulmonary parenchyma involvement(primary, methastatic)

Intrinsic or extrinsic airway obstruction by tumor

Lymphangitic carcinomatosis

Pleural effusion

Pericardial effusion


Tumoral embolism

Phrenic nerve palsy


Trachea-eusophageal fistula

Chest wall involvement

Dyspnea indirectly caused by cancer




Electrolit disturbances

Pulmonary emboli

Paraneoplastic syndromes


Respiratory muscle dysfunction



Caused by cancer therapy


Radiation pneumonitis

Chemotherapy induced pulmonary fibrosis/ pneumonia

Causes of dyspnea in lung cancer patients
symptomatic treatment of dyspnea
Symptomatic treatment of dyspnea
  • Oxygen
  • Pharmacologic therapy
  • General supportive measures
symptomatic treatment of dyspnea oxygen
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 ?
symptomatic treatment of dyspnea pharmacologic therapy
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

symptomatic treatment of dyspnea opioids
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 .
symptomatic treatment of dyspnea1

Nebulised opioids

Nebulised furosemid



General supportive care


Pulmonary rehabilitation

Symptomatic treatment of dyspnea
symptomatic treatment of dyspnea2
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

Non-productive cough

Codeine 10-20 mg X 4-6

Dekstrometorphan 10-20 mg X 3-6


Levodropropisine75 mg X 3

Dihydrocodeine 10 mg X3

Productive cough



Air humidification


  • Bronchodilators
  • Corticosteroids
  • Nebulised lidocaine
  • Nebulised morphine
  • Nebulised phentanyl


Correction of potential etiologies



Sleep disorders




Symptomatic therapies

Nonpharmacologic therapy; Support group, education

Pharmacologic therapy


Clin Lung Cancer 2006;4:241-249

pharmacological therapy of fatigue
Pharmacological therapy of fatigue
  • Methylphenidate
  • Modafinil
  • Dexmethylphenidate
  • Dextroamphetamine
  • Corticosteroiss
  • Megestrol acetate
  • Donepezil


J Natl Cancer Inst 2008;100:1155

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 ??

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


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

  • Depression is the most common mental health problem encountered in palliative medicine


Relieve uncontrolled symptoms

Supportive psychotherapy

Pharmacologic therapy

NCCN Guideline-2009


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
Predisposing factors:

Opioid-induced neurotoxicity

Brain metastases

Cancer treatment

Psychotropic drugs (Tricyclic antidepressants, benzodiazepines)

Metabolic (increased calcium, decreased sodium, renal failure)

Paraneoplastic syndromes



Treatment of predisposing factors



Clorpromasine, olanzepine,risperidon




end of life patient expect
End of life; patient expect
  • Having symptomps under control
  • Being able to breath comfortably
  • Being able to feeding her/himself
  • Preperation for death
  • Having energy to do things one wants to do
  • Good relationship with healthcare professionals

Ann Intern Med 2000;132:825-32

J Pain Symptom Manage 2001 22:717-726


Measures of aggressiveness of care in patients who died of lung cancer in 2002

Died in acute care hospital bad % 59.5 (58.3-60.8)

At least one visit to the emergency

room in last two week % 32.2 (31-33.4)

Admitted to the intensive care unit in

last two week % 5.5 (4.9-6.1)

Received a chemotherapy injection

İn the last 2 weeks % 4.6 (4.1-5.2)

end of life patient care where
End of life patient care: Where?

Components palliative care service

  • Hospice
  • Home care
  • Out patient clinic
  • Inpatient clinic