F. S. Farhat 1
INTRODUCTION
Pain in oncology, and especially in
patient with advanced disease, is an
essential issue which cannot be over-
looked,
Very complex symptom which includes
different aspects such as somatic,
spiritual, social and psychological pain,
F. S. Farhat 2
INTRODUCTION
30% of patients undergoing active
treatment and 70% of patients with
advanced untreatable disease suffer
pain due to tumor progression,
Recent surveys- cancer pain is less
than optimally controlled, physicians‘
knowledge/attitudes in management of
pain contribute to under-treatment,
F. S. Farhat 3
INTRODUCTION
Difficult pain problems associated with
rapidly progressive disease, very severe
pain, or pain syndroms relatively
resistant to opiod analgesics can be an
obstacle to good pain relief in a
proportion of patients which still
unknown, and estimated to range from
20% to 30%.
F. S. Farhat 4
PAIN ASSESSMENT
Clinical assessment
The patient’s complaint should, as a
rule, be believed,
More than one pain with different
pathophysiologies is common,
70% of patient with cancer pain present
at least two pain sites and about 60%
experience episodes of breakthrough
pain,
F. S. Farhat 5
PAIN ASSESSMENT
Clinical assessment
List of all previous treatments, their
analgesic efficacy and side effects is
very useful,
Doses and modality of administration: to
be reviewed / premature conclusion
drug « does not work »,
Psychological and psychosocial history/
implement comprehensive plan of care,
F. S. Farhat 6
PAIN ASSESSMENT
Clinical assessment
Neurological exam/ evaluate the
presence of neuropathic pain and of
neurological complications of the
disease,
2266 cancer patients with pain 34% had
a neuropathic pain,
More than 50% of all the new diagnoses
/ neurologic pain syndromes.
F. S. Farhat 7
PAIN ASSESSMENT
Pain measurement
Pain intensity is measured to help in
monitoring therapy results and to
improve communication with the patient,
Intensity Scales are visual analogue
Scales (VAS), numerical Scales (NRS)
verbal rating Scales (VRS).
F. S. Farhat 8
PATHOPHYSIOLOGY OF PAIN IN
CANCER
Is due to the tumour in 70% of cases,
Not related to the tumour nor to
treatment in less than 10% of cases,
Acute, subacute and chronic pain
syndromes can be due to surgery,
radio- and chemotherapy.
F. S. Farhat 9
Tables 2+3
F. S. Farhat 10
PATHOPHYSIOLOGY OF PAIN IN
CANCER
Differential diagnosis between tumour
recurrence and post-treatment
syndrome : important aspect of pain
evaluation but in most cases it is
relatively simple.
F. S. Farhat 11
PATHOPHYSIOLOGY
Nociceptive pain
Result from the activation of nociceptors
in somatic or visceral structures.
Related to the location and extent of
tissue damage.
Somatic pain / sharp, aching, throbbing
or pressure-like,
F. S. Farhat 12
PATHOPHYSIOLOGY
Nociceptive pain
Visceral pain / poorly localized, gnawing
or cramping, viscus or aching or sharp,
Somatic nociceptive pain usually
responds well to all forms of analgesic
therapy.
F. S. Farhat 13
PATHOPHYSIOLOGY
Neuropathic pain
Results from changes in the
physiological response of neurons in the
central or peripheral somatosensory
system due to chronic stimulation or to
a lesion of the nervous system,
Sensory abnormalities such as
dysesthesia, allodynia or hyperalgesia.
burning or stabbing sensations,
F. S. Farhat 14
PATHOPHYSIOLOGY
Neuropathic pain
Substrate : peripheral nerve lesions
caused by tumour, surgery or
chemotherapy,
Variable response to opioid analgesia,
limited value to neurolytic blockade,
Important role in treating : adjuvant
analgesics.
F. S. Farhat 15
PATHOPHYSIOLOGY
Idiopathic pain
unknown origin.
example : psychogenic pain which is
uncommon in cancer patients.
F. S. Farhat 16
CANCER PAIN SYNDROMS
Bone Pain
Most common cause of pain in cancer,
Bone metastases occur in 30 to 70% of
all patients with cancer,
Mechanism : unknown, stimulation of
periosteal nociceptors ?,
Pain on activity: sign of abnormality of
bone structures, potential for fracture,
F. S. Farhat 17
CANCER PAIN SYNDROMS
Bone Pain
Often reported in the body area,
A variety of bone pain syndromes can
be found according to different tumours
under evolution.
F. S. Farhat 18
Table 5
F. S. Farhat 19
Bone Pain / Bone marrow expansion,
bone marrow infiltration syndrome.
Difficult to diagnose - X-ray, even MRI
imaging are often difficult to interpretate,
Pain : generalized and migrating, often
fluctuates in intensity,
Haematological malignancies, rarely
diffuse marrow infiltration by solid
tumours (breast, melanoma).
F. S. Farhat 20
Bone Pain
Vertebral pain syndromes.
Most common sites of bone
metastases; multiple, involve the
vertebral body first,
Thoracic spine >2/3, lombosacral spine
in 20%, cervical spine in 10% of cases.
complication: vertebral collapse,
radiculopathy, ESCC.
F. S. Farhat 21
Bone Pain
Epidural spinal cord compression.
Most dangerous complication of
vertebral metastases,
Catastrophe for patient’s quality of life,
In 5 to 10% of patients with cancer,
Posterior extension of tumour into a
vertebral body (solid tumours), invasion
of the epidural space through the inter-
vertebral foramina (lymphoma ),
F. S. Farhat 22
Bone Pain
Epidural spinal cord compression
A radiographic abnormality can predict
epidural invasion in 60% of the cases in
patients with back pain and a normal
neurologic exam,
Best imaging approach : MRI. CT
myelogram and standard myelography :
alternate procedures of choice.
F. S. Farhat 23
Headache due to intracranial tumor
Brain metastases : in 25% of the
patients who die of cancer,
Headache : in about 50% of cases,
May or may not be associated with an
increased intracranial pressure,
Associated with vomiting; (morning,
valsava).
F. S. Farhat 24
Base of the skull syndromes
Metastases are common from breast,
prostate and other tumours,
Headache is felt at the site of the lesion
or referred to the vertex or to the entire
affected side of the head.
F. S. Farhat 25
(table 8)
F. S. Farhat 26
Pain due to lesions of the nervous
tissue/Facial pain, nerve lesions.
Can be a manifestation from infiltration
of cranial nerves by locally advanced
head and neck carcinomas,
Manifestation of base of skull lesions or
of leptomeningeal metastases.
F. S. Farhat 27
Pain due to lesions of the nervous
tissue / Cervical plexopathy
Infiltration of the cervical plexus results
from direct compression by head and
neck neoplasms, metastases to cervical
nodes,
Local pain with lancinating or
dysesthetic components.
F. S. Farhat 28
Pain due to lesions of the nervous
tissue / Brachial plexopathy
Breast and lung carcinomas and
lymphomas are the most common
cause of brachial plexopathy,
In 85% of cases pain is first symptom
preceding other neurological symptoms
by weeks to months.
F. S. Farhat 29
Pain due to lesions of the nervous
tissue / Polyneuropathies
Painful polyneuropathies :
chemotherapy neurotoxicity, rarely, to
paraneoplastic syndromes,
Painful peripheral neuropathies :
stocking-glove distribution of negative-
hypoesthesia, positive sensory (burning
dysesthesia, hyperalgesia) symptoms,
F. S. Farhat 30
Pain due to lesions of the nervous
tissue / Polyneuropathies
Vincristine, paclitaxel and
paraneoplastic sensory neuropathies :
typically painful,
Cisplatin induced polyneuropathy : is
rarely painful.
F. S. Farhat 31
Pain due to lesions of the nervous
tissue / lumbosacral plexopathy
Pain presenting symptom 93%, precede
other neurological symptoms bymonths,
followed by the onset of numbus,
paresthesias, weakness, leg edema,
Often associate bone lesion,
Can occur after pelvic radiation,
Procedure of choice to image the
lumbosacral plexus: MRI, Ct scanning.
F. S. Farhat 32
Chest wall pain
Typical for lung tumours : due to
infiltrating of the parietal pleura,
Unilateral pain - 80%, bilateral - 20% ,
Hilar tumors- pain in the sternum or the
capsula, upper and lower lobe tumors:
shoulder and lower chest,
Progression:invasion of ribs, intercostal
nerves, vertebrae, brachial plexus.
F. S. Farhat 33
Visceral pain and retroperitoneal
syndromes
Visceral tumour infiltration was the
second most common cause of pain
cancer patients (Martini / Milano ),
F. S. Farhat 34
Table10.
F. S. Farhat 35
Pelvic and perineal pain
Perineal pain can be for a long time the
only symptom of pelvic tumours
Results from early perineural tumour
infiltration, often associated with
tenesmus,
Prostate, cervix and rectal tumours :
most frequent,
F. S. Farhat 36
Pelvic and perineal pain
Fistulas and recurrent infection can
aggravate the pain syndrome,
Direct invasion of the sacrum, sacral
roots, lumbosacral plexus or cauda
equina are frequent complicatons.
F. S. Farhat 37
PHARMACOLOGIC PAIN
MANAGEMENT
Drug therapy can control pain in 70-90
% of patients with chronic cancer pain,
WHO analgesic ladder: analgesic drugs
are selected in a stepwise fashion
based on the overall severity of pain,
Adjuvant drugs may be added at any
step to treat side effect or other
symptoms, or as adjuvant analgesics.
F. S. Farhat 38
The three-step analgesic ladder of who,
1996, Geneva.
fig 2
F. S. Farhat 39
Nonsterodial anti-inflamatory drugs
There action is both peripheral and
central,
The combination with an opioid
produces additive analgesic effects, can
be useful in optimizing the balance
between analgesia and side effects,
F. S. Farhat 40
Nonsterodial anti-inflamatory drugs
NSAID efficacy is limited: ceiling effect,
Some patients do respond electively to
NSAID better than to opioid analgesia,
Side effects must be closely monitored
during NSAID therapy, especially when
using higher doses.
F. S. Farhat 41
Paracetamol
Its mechanism is probably central,
Analgesic at the same level as NSAIDs
in cancer pain management (1st step),
Effective analgesic, especially at higher
doses 1000mg oral or iv dose/4 hours,
Lower doses are included in many
combination with opioids such as
codeine and oxycodone,
F. S. Farhat 42
Paracetamol
Lack of anti-inflammatory activity is
probably a disadvantage in cancer pain
syndromes / peripheral inflammatory
mechanisms contribute to generate
pain,
No gastric nor thrombocytic toxicity.
Hepatic toxicity is possible, dose
related.
F. S. Farhat 43
Opioid analgesics
Classified according to the receptor
interactions :
Agonist-antiagonist drugs : limited role
in management of chronic cancer pain,
Agonist opioid drugs of morphine type :
mainstay of cancer pain management.
F. S. Farhat 44
Opioid analgesics
Step II of the WHO analgesic ladder
Table 13 reports what are typical step II
analgesic regimens,
Are usually given in combination with
acetaminophen or aspirin,
The dose of these combination products
cannot exceed the maximum safe dose
of non-opioid compound (example :
6000 mg/day for acetaminophen),
F. S. Farhat 45
Table 13
F. S. Farhat 46
Opioid administration
First line approach
Step II according to the WHO ladder :
Patients with limited opioid exposure
and moderate pain : combination of an
opioid and non-opioid analgesic- first
choice,
Table 13 can be a useful guide to clarify
most common step II therapies,
F. S. Farhat 47
Table 13
F. S. Farhat 48
Opioid administration
First line approach
Severe pain or of insufficient analgesia
with a second step drug oral morphine
or a morphine like agonist : the
preferred indication,
Table 15 : the main step in initiating an
oral morphine regimen,
F. S. Farhat 49
Table 15
F. S. Farhat 50
Routes of administration
The oral route
Efficacious, simple and acceptable for
most patients,
Alternative routes necessary: GI tract
dysfunction, rapid onset or titration of
analgesia, occurrence of side effects,
Side effects should be aggressively
treated before switching the route of
administration or the drug.
F. S. Farhat 51
Routes of administration
Continuous infusion (sc, iv)
In case of dysphagia, GI obstruction,
nausea and vomiting with oral opioids,
Reduces the fluctuations in plasma
concentration (stable plasma levels),
May help maintain stable plasma levels
between efficacy and side effects,
Is very simple,
F. S. Farhat 52
Routes of administration
Continuous infusion (sc, iv)
In a study (Ventafridda 1986), effective
in 80% of the cases in which SCI was
performed in the hospital and at home,
In one case series, 94% of the patients
preferred SCI to previous therapies, in
another study, 16% preferred an
alternative treatment: psychological
intolerance toward infusion devices,
F. S. Farhat 53
Routes of administration
Continuous infusion (sc, iv)
Cutaneous reactions at injection site: 9-
13%, easily managed by changing the
injection site. The tolerability of the SC
needle is 7.3=/-5.2 days.
Certainly morphine is the most widely
used opioid drug in SCI.
(Hydromorphone in united states,
Diamorphone in great britain).
F. S. Farhat 54
Routes of administration
Continuous infusion (sc, iv)
No differences in terms of side effects
between IV and SC infusion (double-
blind cross-over study), plasma
concentrations is comparable.
Considering the technical advantages of
SC technique, IV opioid infusion for
severe cancer pain should be reserved
for cases with specific indications.
F. S. Farhat 55
Routes of administration
Continuous infusion (sc, iv)
Continuous SC or IV infusions can be
used in the home care of patients with
advanced cancer in which pain is
associated with other symptoms
(vomiting).
3 :1 ratio for oral versus parenteral
morphine.
F. S. Farhat 56
Patient controlled analgesia:
In recent years : popularity because of
wide individual responsiveness to
analgesics,
Suited to patient needs, better pain
relief without increasing side effects or
substantially inferior doses to obtain the
same pain relief from external dosing,
F. S. Farhat 57
Patient controlled analgesia:
Independence from staff intervention,
close titration of analgesia to individual
needs: main theoretical advantages ,
Advantage: sense of self-control over
pain and the overall situation. In other
cases, the responsibility of controlling
one’s pain and the fear of drug abuse
can trigger anxiety and insecurity.
F. S. Farhat 58
Spinal opioid administration :
Can potentially yield analgesia at much
lower doses,
True however only within a very limited
range of dosing in non tolerant patients,
Techniques may be indicated for
patients with opioid responsive pain
who experience excessive side effects
on systemic therapy.
F. S. Farhat 59
Transdermal administration
published clinical experience is growing,
Efficacy and safety of this approach,
Route alternative to IV and SC infusion
in GI tract dysfunction, patient confort,
freedom from frequent dosing ,
Available transdermal patches: 25, 50,
75 or 100 g/hour of fentanyl.
F. S. Farhat 60
Transdermal administration
Combine different patches to achieve
the desired dose, dosing interval = 72 h,
Pic plasma concentration : reach 24-48
h, efficacy+ toxicity- during the first day,
Recent studies : transdermal fentanyl :
equal efficacy to oral morphine, and
reduced incidence of constipation,
nausea. suggested ratio : 1/150.
F. S. Farhat 61
Rectal route :
Patients who lack the oral route, are
receiving transdermal or parenteral
routes,
Available for morphine, oxymorphone
and hydromorphone,
The bioavailability is similar to oral
administration and relatively erratic.
F. S. Farhat 62
Treatment of Opioid Side Effect.
Goal of opioid therapy- favorable
balance between analgesia and side
effects. The treatment of opioid side
effect is, therefore an integral part of
treatment,
Table 16 give practical guidelines for
managing frequent and opioid side
effects.
F. S. Farhat 63
Table 16
F. S. Farhat 64
Opiod resistant pain
No response or an insufficient analgesic
response despite an upward titration of
full agonist opioids through a reliable
administration route (iv) to the point of
unacceptable CNS side effects.
Most cases of of unresponsive opioid
pain can be managed by appropriate
upward titration, changing route of
administration, F. S. Farhat 65
Opiod resistant pain
In some pain syndromes there is an
unfavorable response to opiod therapy:
neuropathic pain, perineal pain with
rectal and vesical tenesmus,
With selected patients pain pathway
blocks can be considered, adjuvant
analgesics should be tried.
F. S. Farhat 66
ADJUVANT ANALGESICS
Some of these drugs have primary
indications other than analgesia, but are
analgesics in selected circumstances
and pain syndromes for which they are
given as primary pain therapy.
F. S. Farhat 67
ADJUVANT ANALGESICS
Tricyclic antidepressants
Analgesic effect- proven in typical
neuropathic pain syndromes such as
diabetic neuropahty and post herpetic
neuralgia,
Analgesic effect- seen much earlier than
antidepressants effect,
F. S. Farhat 68
Table 17
F. S. Farhat 69
ADJUVANT ANALGESICS
Anticonvulsants and baclofen
The pharmacokinetic interaction with
morphine should be kept in mind. The
analgesic effect is well established in
trigeminal neuralgia,
Cancer pain with lancinating or
paroxysmal dysesthesias,
Carbamazepine: 400 - 1600 mg/day,
F. S. Farhat 70
ADJUVANT ANALGESICS
Corticosteroids
Relieving pain, improving appetite,
nausea, mood and overall quality of life
in advanced cancer patients,
Raised intracranial pressure, spinal cord
compression, superior vena cava
syndrome, metastatic bone pain, nerve
compression,symptomatic lymphedema
and hepatic capsular distension.
F. S. Farhat 71
ADJUVANT ANALGESICS / Adjuvants
used in treatment of bowel obstruction
Is frequent complication of advanced
abdominal cancer,
When is not surgically reversible, the
management of pain and associated
symptoms (vomiting) can be
accomplished using drugs (continuous
SC or IV infusions),
F. S. Farhat 72
ADJUVANT ANALGESICS / Adjuvants
used in treatment of bowel obstruction
Anticholinergic drugs, like Scopolamine,
have been effective reducing colicky
pain and vomiting,
Octeorid, effective in reducing vomiting
in patients with bowel obstructions.
F. S. Farhat 73
ADJUVANT ANALGESICS
Biphosphonate for bone pain :
Inhibit osteoclastic activity,
Clodronate : advantage in terms of relief
of bone pain : 30 to 50 % of patients,
Pamidronate analgesic activity dose
dependent, with about 60% of patients
reporting relevant pain reduction with 60
and 90 mg 4-weekly regimens,
F. S. Farhat 74
ADJUVANT ANALGESICS
Biphosphonate for bone pain :
Early prophylactic use of pamidronate :
recommended to reduce the
complications related to bone disease:
pain, fractures, spinal cord
compression,
The cost of these agents should
however be considered,
Poor oral bioavailibility.
F. S. Farhat 75