Support Care Cancer (2015) 23:1473–1481
DOI 10.1007/s00520-015-2678-9
REVIEW ARTICLE
Pharmacological options for the management of refractory
cancer pain—what is the evidence?
B. Afsharimani & K. Kindl & P. Good & J. Hardy
Received: 21 November 2014 / Accepted: 22 February 2015 / Published online: 7 March 2015
# Springer-Verlag Berlin Heidelberg 2015
Abstract Refractory cancer pain that does not respond to
standard opioid and/or co-analgesic therapy occurs in 10–
20 % of patients. Risk factors include young age, neuropathic
pain type, incident pain, psychological distress, previous opi-
oid use, high tolerance, a history of addiction and impaired
cognition. The management of patients with refractory pain
remains a challenge. Treatment options include opioid manip-
ulation (parenteral delivery, rotation, combination, methadone
and buprenorphine), non-opioids and co-analgesics (paracet-
amol, non-steroidal anti-inflammatory agents, antidepressants
and anticonvulsants), NMDA receptor antagonists, cannabi-
noids, lignocaine and corticosteroids. The evidence of benefit
for any of these agents is weak, and each additional agent
increases the risk of adverse events. Evidence-based guide-
lines cannot, therefore, be developed at present. New ap-
proaches are recommended including targeted opioid therapy,
multimodal analgesia, a goal-oriented approach to pain man-
agement and increasing use of the multidisciplinary team and
support services.
Keywords Cancer pain . Refractory . Evidence . Analgesia
Introduction
World Health Organisation (WHO) analgesic guidelines rec-
ommend a limited number of drugs titrated in a step-wise
B. Afsharimani : K. Kindl : P. Good : J. Hardy (*)
Department of Palliative and Supportive Care , Mater Health
Services, and Mater Research Institute, University of Queensland,
Brisbane, Australia
e-mail: janet.hardy@mater.org.au
P. Good
St Vincent’s Private Hospital, Brisbane, Australia
fashion according to the severity of pain [1]. These guidelines
are considered the world standard for pain control. It is gen-
erally accepted that the use of these guidelines results in the
control of pain in the majority of patients [2].
Refractory cancer pain has been defined as pain related to
cancer or its treatment, of at least 3 months duration, that has
not responded to standard treatment with opioids and co-
analgesics [3]. There is no standard definition however, and
cancer pain that is difficult to control has been variously de-
scribed as difficult, persistent, intractable or opioid non-
responsive in heterogeneous populations exposed to a range
of different medications and interventions. It has been report-
ed to occur in 10–20 % of cancer patients. [4]. The character-
istics that lead to difficult pain control are said to include
young age, neuropathic pain type, incident pain, psychologi-
cal distress, previous opioid use, high tolerance, a history of
addiction and impaired cognition [5]. The prognosis of cancer
pain is reported to be worse in those with mixed pain type,
high pain severity, daily opioid use and poor emotional well-
being [5]. With the goal of developing evidence-based guide-
lines for refractory cancer pain management, the evidence for
the treatments and interventions commonly used for refractory
cancer pain was examined.
Methods
Strategies for the management of refractory cancer pain were
obtained from a survey of palliative care physicians [6], from
reviews of refractory cancer pain management [7] and from
personal experience of the authors and palliative care col-
leagues. Evidence for the effectiveness of each intervention
was sought primarily from the Cochrane data base and from
published systematic reviews searched via Cochrane,
EMBASE, PUBMED and the Joanna Briggs Institute. In the
absence of a formal Cochrane review, systematic reviews,
1474
randomised and non-randomised controlled trials were accept-
ed. Unless specified otherwise, all trials discussed are
randomised controlled trials (RCTs). The quality of included
studies was not formally assessed or scored. Non-
pharmacological interventions including interventional tech-
niques, complementary therapies and psychological support
have not been included and will be the subject of a subsequent
review.
Results
Opioids
Opioids remain the only analgesics with proven benefit in
severe cancer pain [8, 9]. Opioid dose escalation in the face
of increasing pain is often limited by adverse effects. Several
approaches have been proposed to address this including the
proactive and aggressive management of side effects, the use
of co-analgesics, alternative routes of administration or
switching to a different opioid (opioid rotation) [10].
Parenteral opioids
High serum concentrations of opioids can be achieved rapidly
by parenteral administration although the correlation between
serum opioid concentrations and analgesia is poor [11–13].
Clinical studies have shown similar efficacy and tolerability
for both intravenous and subcutaneous delivery [14]. Subcu-
taneous injection is generally preferred due to ease of admin-
istration, but the intravenous route can provide faster pain
relief [15].
Few studies have explored the possibility that refractory
cancer pain responds to a rapid and intensive analgesic inter-
vention. In a small open-label RCT assessing the use of par-
enteral morphine titration for pain exacerbations, pain was
controlled in 77 % of the cases with no difference between
the subcutaneous and intravenous routes [16]. In patients with
severe pain from advanced cancer, intravenous morphine was
shown to be safe and to result in better immediate analgesia
than oral morphine [17].
The peak onset of action of morphine is seen after about
30 min, even when administered intravenously [18]. More
lipophilic opioids such as fentanyl readily cross the blood
brain barrier and provide effective analgesia more rapidly.
One small RCT studied the benefit of subcutaneous fentanyl
compared to morphine in cancer patients and found both drugs
to be equally efficacious [19]. An uncontrolled observational
study in patients seen in emergency rooms with severe pain
showed fast opioid titration with bolus intravenous fentanyl to
be safe and effective in controlling pain [20]. A retrospective
analysis of cancer patients commenced on subcutaneous fen-
tanyl infusions because of toxicity or uncontrolled pain from
Support Care Cancer (2015) 23:1473–1481
other opioids or routes of administration found subcutaneous
fentanyl to be well tolerated and effective in the management
of refractory pain [21]. In a small retrospective study of cancer
patients who could not tolerate subcutaneous morphine, sub-
cutaneous fentanyl infusion was used to achieve analgesia
with limited side effects [22].
At present, there is no evidence to support the superiority of
parenteral versus oral opioid administration in controlling in-
tractable cancer pain. Based on available evidence, the Euro-
pean Association of Palliative Care (EAPC) recommends the
use of parenteral opioid infusions in cases where oral or trans-
dermal opioids fail to provide effective analgesia [15].
Opioid rotation
Changing or switching from one opioid to another has been
reported in many uncontrolled trials and descriptive studies to
lead to improved pain relief and/or reduction in toxicity. Pro-
posed mechanisms include incomplete cross-tolerance, varia-
tion in intrinsic opioid receptor activity, inter and intra-patient
variation in pharmacokinetics/dynamics and relative
desensitisation of opioid receptors [23].
A Cochrane review identified multiple case studies, retro-
spective reviews and prospective uncontrolled trials all of
which showed benefit [24]. None of the studies was of suffi-
cient quality to be included in a meta-analysis. A subsequent
systematic review identified eleven new trials, of which the
majority showed opioid switching to be highly effective in
controlling cancer pain and reducing adverse effects [25].
All of the studies were of limited quality and lacked
randomisation or controls.
Opioids in combination
Theoretically, patients with pain refractory to a single opioid
might benefit from the addition of a second opioid, especially
when using drugs with different characteristics such as differ-
ent lipid solubility, routes of metabolism, degree of receptor
activation/antagonism or opioid receptor type affinity. Animal
studies have confirmed the benefit of using a combination of
different opioids in improving analgesia and reducing depen-
dence [26]. Human studies on the benefit of combination opi-
oid analgesia are contradictory. A prospective clinical trial
comparing combination opioid therapy and opioid rotation
in cancer patients with uncontrolled pain showed similar ben-
efit in pain reduction and adverse effects for both manoeuvres
[27]. In contrast, a systematic review on the efficacy and safe-
ty of a combination of strong opioids in controlling cancer
pain included two studies that showed better pain relief and
lower side effects when a second opioid was added to the
original [28]. Unfortunately, due to methodological problems
in study design, only a weak recommendation could be made
Support Care Cancer (2015) 23:1473–1481
towards the use of combination strong opioids in controlling
cancer pain.
Methadone
Methadone is often used as a second-line agent in difficult
pain, instead of, or in conjunction with, other opioids. Inhibi-
tion of NMDA receptors and monoamine reuptake plus acti-
vation of kappa and delta opioid receptors is postulated to lead
to additional analgesia and reversal of opioid tolerance. Anec-
dotally, methadone has benefit in patients with predominantly
neuropathic pain [29].
This opioid is difficult to use because of significant inter-
patient variation in efficacy and unpredictable adverse effects.
Dose titration is complex due to the highly variable pharma-
cokinetic profile of the drug. Patients must be closely moni-
tored because of the possibility of drug accumulation and
unintended overdose. Methadone is frequently used in the
scenario of opioid rotation or switching. The morphine dose
equivalence of methadone is not clear. It has been suggested
that the morphine-to-methadone equipotent ratio varies de-
pending on the prior dosage of opioids administered, and that
in patients on higher doses of morphine, lower doses of meth-
adone are needed to achieve the same analgesic effect [30].
A Cochrane review of methadone versus opioid compara-
tors included nine RCTs and 459 participants. A number of
different dose and titration schedules were used along with
various pain scales. No superiority over morphine was shown
nor superiority with respect to the treatment of neuropathic
pain. Patients on methadone had a higher rate of withdrawal
due to adverse events [31].
More recently, two RCTs showed a benefit for switching to
methadone. In cancer patients with refractory pain, sustained-
release morphine, methadone and transdermal fentanyl were
similarly effective in controlling pain, but the need for opioid
escalation was significantly less with methadone [31]. A com-
bination of epidural methadone and lidocaine has been com-
pared to epidural lidocaine alone in cancer patients whose pain
was not adequately controlled with oral morphine. The addi-
tion of methadone to lidocaine reduced the need for oral mor-
phine consumption in a dose-dependent manner. This was
improved when epidural dexamethasone was added to the
regimen [32].
The additive effect of acetaminophen on the analgesic ef-
ficacy of methadone in cancer patients has been studied. Par-
ticipants were switched from a stable dose of morphine to
methadone and plus either acetaminophen or placebo. Al-
though acetaminophen showed no advantage over placebo,
switching to methadone significantly improved pain scores,
constipation and xerostomia [33]. Switching to methadone
from other opioid analgesics was also shown to be safe and
effective in a prospective uncontrolled study in 21 opioid-
tolerant cancer patients [34]. In a prospective uncontrolled
1475
study in patients with advanced cancer, switching to metha-
done from oxycodone was successful in improving pain and/
or adverse effects and distress [35].
Methadone may contribute to the management of refracto-
ry pain, but to date, there remains considerable uncertainty
regarding dose equivalence, how best to titrate and concern
over potential toxicity.
Buprenorphine
Buprenorphine is a semi-synthetic partial agonist of the mu
opioid receptor with proven efficacy in controlling chronic
pain. In patients requiring escalating doses of opioids for pain
management, buprenorphine may stabilise opioid dosing, pro-
vide effective pain relief and improve quality of life (QoL)
[36].
Transdermal buprenorphine has been shown to have a more
favourable adverse effect profile compared to pure mu ago-
nists such as morphine or fentanyl [37, 38]. Buprenorphine
transdermal patches resulted in better analgesia compared to
placebo and rescue buprenorphine in 157 patients with severe
uncontrolled pain from cancer or other disorders [39]. In 137
patients (including 45 cancer patients) with severe chronic
pain, there was a trend towards better pain relief in patients
randomised to transdermal buprenorphine [40]. Compared to
placebo (with rescue analgesia), transdermal buprenorphine
administration resulted in lower pain intensity, less need for
rescue analgesics and fewer discontinuations [41]. In an open
observational surveillance study in 13,179 patients with
chronic pain (including 3690 cancer patients), effective pain
relief, good tolerability and less need for rescue therapy were
seen in patients receiving buprenorphine patches [42].
Compared to sustained-release morphine administration,
transdermal buprenorphine was more effective in providing
long-term pain control and improving QoL in cancer patients
assessed by a randomised prospective study [43].
Buprenorphine is also reported to be effective in control-
ling neuropathic and breakthrough pain in cancer patients and
to be an option in opioid rotation [37]. Unfortunately, three
systematic reviews have concluded that due to the poor quality
of evidence, a definitive conclusion cannot be made on the
efficacy of this drug in moderate-to-severe cancer pain
[44–46].
Non-opioid analgesics and co-analgesics
The WHO analgesic ladder supports the use of non-opioid
analgesics (paracetamol and NSAIDs) and adjuvant analge-
sics as monotherapy for mild cancer pain and as adjunct for
improving opioid analgesia in moderate-to-severe pain in can-
cer patients [47].
1476
Paracetamol and NSAIDs
Paracetamol and/or NSAIDs are used in patients with cancer-
related pain because of their postulated opioid-sparing effect
[48, 49]. Although effective in mild to moderate cancer pain,
these preparations have limited value in severe pain as dose
escalation is restricted by adverse effects. A Cochrane review
found 14 studies that compared the efficacy of opioids and
NSAIDs or paracetamol, alone or in combination, in cancer
pain. Nine studies showed a slight advantage, one insignifi-
cant advantage and four no advantage for combinations of
opioids and NSAIDs/paracetamol over each drug used alone
[50]. A more recent systematic review identified two other
studies that showed a benefit of adding NSAIDs/paracetamol
to an opioid analgesic regimen in cancer patients [48]. One
RCT assessed the outcome of adding oral ketorolac to mor-
phine treatment in patients with advanced cancer. Ketorolac
(60 mg/day) led to better analgesia and reduced the need for
opioid dose escalation [51]. The introduction of dipyrone to a
morphine regimen significantly improved analgesia compared
to placebo in another small RCT [52].
In summary, NSAIDs can have an opioid-sparing effect
and might improve analgesia. However, since clinical studies
are of insufficient number or quality, they can only weakly
support the use of NSAIDs as co-analgesics in the manage-
ment of cancer pain [48].
Antidepressants
Neuropathic pain accounts for about one third of refractory
pain associated with cancer [5]. Opioid analgesics alone often
fail to control pain completely [7]. Historically, antidepres-
sants have been used as co-analgesics for the management
of neuropathic pain. Any analgesic effect is independent of
the psychological impact and is thought to be due to enhanced
norepinephrine and serotonin-mediated descending inhibitory
output and possibly blockade of sodium channels [53]. The
evidence of benefit in the management of pain comes largely
from trials of non-malignant pain.
A Cochrane review of tricyclic antidepressants in all pain
types suggested that the number needed to treat (NNT) for at
least moderate pain reduction was 3.6. The number needed to
harm (NNH) for minor and major adverse events was 3.7 and
22, respectively. These results are similar to those for the
newer antidepressants such as venlafaxine (NNT=3.1) [54].
A systematic review of amitriptyline showed evidence of ben-
efit in some non-malignant pain scenarios but failed to find
any unbiased well-designed clinical studies to support its use
in cancer pain, [55]. Duloxetine has been shown in three
double-blind RCTs to be effective in controlling diabetic pe-
ripheral neuropathic pain [56].
Very few studies have been performed in cancer-related
neuropathic pain. Three small RCTs of venlafaxine [57, 58]
Support Care Cancer (2015) 23:1473–1481
and amitriptyline [59] in treatment-related neuropathic pain in
cancer patients demonstrated effectiveness. In patients with
advanced cancer, there was no improvement in pain control
when amitriptyline was added to an opioid analgesic regimen
[60]. In pain related to bone metastases, a combination of low-
dose antidepressants (imipramine or mirtazapine) with an an-
ticonvulsant (pregabalin) provided better pain control com-
pared to pregabalin alone [61]. There is recent evidence for
the benefit of duloxetine in chemotherapy-induced painful
peripheral neuropathy [62].
A systematic review analysed 14 RCTs and 16 non-
randomised studies of neuropathic cancer pain based on abso-
lute risk benefit and absolute risk harm. Overall, absolute risk
benefit of antidepressants, anticonvulsants, other adjuvant an-
algesics or opioids outweighed absolute risk harm [63].
Although guidelines recommend using antidepressants for
neuropathic pain especially in cancer patients with mood dis-
orders, rigorous data are lacking to endorse the use of antide-
pressants as co-analgesics in cancer pain and current practice
is mainly based on clinical experience.
Anticonvulsants
Anticonvulsants, particularly gabapentin and pregabalin, are
commonly used as first-line treatment in neuropathic pain
[64]. Their effect is thought to be exerted through binding to
presynaptic calcium channels, decreasing calcium influx and
neurotransmitter release [65].
A systematic review that analysed five RCTs and three
non-randomised studies on the benefit of combining antide-
pressants or antiepileptic drugs with opioid analgesics in neu-
ropathic cancer pain found the strongest evidence for the ef-
fectiveness of gabapentin [66] although a recent RCT showed
similar analgesic efficacy for both gabapentin and amitripty-
line when used as co-analgesics in this setting [67]. In a RCT
in cancer patients, neuropathic pain intensity was significantly
lower in patients treated with pregabalin as compared to pla-
cebo [68]. Similarly, pregabalin provided better control of
neuropathic cancer pain compared to placebo, gabapentin or
amitriptyline and reduced opioid consumption [69].
Pregabalin also provides better pain relief and patient satisfac-
tion compared to transdermal fentanyl [70]. High quality con-
trolled trials are still needed to support the safety and efficacy
of these drugs in cancer patients [71].
N-methyl-D-aspartate (NMDA) receptor antagonists
Ketamine is a general anaesthetic agent that is often used at
subanaesthetic doses as a co-analgesic, usually in combination
with opioids, particularly in neuropathic pain [72]. It interacts
with multiple receptors thought to be involved in pain percep-
tion. NMDA receptor activation is thought to result in neuro-
nal hyperexcitability and the development of opioid tolerance.
Support Care Cancer (2015) 23:1473–1481
Ketamine has been used commonly in palliative care for the
management of refractory or difficult pain, usually in combi-
nation with opioids [73]. There is great variation in practice
with respect to the type of pain treated with this drug, the dose,
route and frequency of delivery.
A Cochrane review updated in 2012 included two RCTs
that evaluated the effectiveness of adding ketamine to opioids
in cancer patients with refractory pain. Both studies found
ketamine administered intravenously [74] or intrathecally
[75] to be effective in improving analgesia. Pooling of data
was not possible due to the small size and clinical heteroge-
neity of the studied populations. The review concluded that
the current evidence was insufficient to support the use of
ketamine as an adjuvant to opioids for refractory cancer pain
[76].
More recently, two multicentre double-blind RCTs found
no benefit for the addition of ketamine to opioids in treating
cancer pain. The effect of parenteral ketamine as an adjuvant
analgesic was studies in 185 adult patients with refractory pain
due to cancer or its treatment. Ketamine did not result in any
improvement in pain over placebo and was associated with
significantly more adverse events [4]. The other RCT, per-
formed in a smaller number of patients, compared analgesic
outcome after intravenous morphine with or without a contin-
uous intravenous infusion of ketamine. The addition of keta-
mine failed to provide any advantage over morphine alone
[77].
Soto et al. reviewed randomised and non-randomised clin-
ical data on the use of oral ketamine in cancer and neuropathic
pain and found mixed results on the safety and efficacy of oral
ketamine in these settings [78]. A recent systematic review
evaluated clinical data on the use of ketamine for cancer pain.
Five RCTs and six uncontrolled studies in adult cancer pa-
tients were included. The findings in relation to effectiveness
were contradictory [79].
Overall, clinical opinion remains divided regarding keta-
mine as adjuvant analgesic in refractory cancer pain. Robust
evidence to support its benefit in this setting is lacking.
Cannabinoids
According to one systematic review, the existing data from
several RCTs suggest that cannabinoids are safe and effective
in controlling different types of chronic pain, particularly neu-
ropathic pain [80]. Activation of cannabinoid receptors at pre-
synaptic sites and interaction with opioid, serotonergic and
dopaminergic signalling are thought to result in an analgesic
effect [81].
Early findings from RCTs published in the 1970s found
moderate analgesic efficacy for cannabinoids in cancer pain,
comparable to codeine, but with dose-limiting adverse effects
[82, 83]. A non-randomised prospective observational study
in patients with advanced cancer suggested that nabinol
1477
decreased pain scores and morphine consumption compared
to untreated patients [84].
Nabiximols (Sativex®) is an oromucosal spray containing
a 1:1 combination of tetrahydrocannabinol (THC), the princi-
pal psychoactive constituent of the cannabis plant and
cannabidiol. It is approved in some countries for the treatment
of neuropathic pain in multiple sclerosis (MS) and refractory
pain in cancer [85]. A placebo-controlled randomised trial
assessed the effect of different doses of nabiximols on
opioid-unresponsive refractory pain in 360 cancer patients.
Low and medium doses of nabiximols were well-tolerated
and improved analgesia after 5 weeks of treatment [86]. The
safety and efficacy of this combination preparation was shown
in another RCT comparing nabiximols and THC with placebo.
While pain scores in patients receiving THC were similar to
placebo, nabiximols significantly reduced pain [87]. This ef-
fect persisted with long-term use as shown by a subsequent
open-label follow-up study [88]. The primary adverse effects
at therapeutic doses are drowsiness, somnolence and dry
mouth, and there remain concerns about psychoactive effects
and potential for addiction and abuse [89]. The limited avail-
ability of cannabinoids in many countries precludes its use for
refractory pain in most situations.
Lignocaine
Lignocaine, a local anaesthetic used topically to relieve per-
sistent focal pain, has been used as an adjunct analgesic in
neuropathic pain caused by cancer or its treatment [89]. Sys-
temic administration of lignocaine and other antiarrhythmic
drugs (such as flecainide and mexiletine) have also been used
for the control of postoperative or cancer pain. Preclinical and
clinical findings have indicated analgesic efficacy for
lignocaine in neuropathic pain [90]. A Cochrane review con-
cluded that current evidence endorses the safety and efficacy
of parenteral lignocaine and its oral analogues in controlling
neuropathic pain [91]. However, as very few studies reported
their outcome in cancer patients, no definite conclusion could
be made about the use of these drugs for the management of
cancer pain.
Corticosteroids
The analgesic effect of corticosteroids, particularly in inflam-
matory and neuropathic pain, may result from inhibition of
cytokine-mediated perception of pain [92]. A systematic re-
view of literature found four RCTs that assessed the outcome
of corticosteroid administration in cancer patients [93]. Two of
these studies did not adequately report the pain outcome [94,
95]; one study showed significant improvement in analgesia
and a reduction of analgesic consumption while another
showed no beneficial effect for corticosteroids [96, 97]. In
another RCT, the addition of epidural dexamethasone
1478
enhanced the analgesic efficacy of epidural methadone and
lidocaine with lower consumption of morphine by cancer pa-
tients with refractory pain [32]. In a more recent study, cancer
patients on opioids were randomised to methylprednisolone or
placebo. Methylprednisolone did not provide additional anal-
gesia but improved fatigue and appetite [98]. Considering the
limited evidence on efficacy in controlling cancer pain and the
potential for serious toxicity with long-term use, a careful risk-
benefit analysis should be undertaken before using corticoste-
roids for cancer pain.
Discussion
The management of refractory cancer pain remains a chal-
lenge. Current strategies often involve the addition of a suc-
cession of unproven medications or interventions to standard
opioids and co-analgesics. Each additional medication has a
reduced likelihood of controlling pain and an increased poten-
tial for added toxicity [3]. As demonstrated in this review,
there is a paucity of high level evidence to guide refractory
cancer pain management. Clinicians are largely reliant on ev-
idence extrapolated from non-cancer pain scenarios, anec-
dotes or uncontrolled and low-quality studies. Unproven in-
terventions should only be considered in the context of a clin-
ical trial or be subject to rigorous prospective evaluation using
standardised tools and data collection systems. The focus of
future pain management should be on new approaches and
optimising the use of currently available drugs and techniques
as illustrated below.
Targeted opioid therapy
Opioids remain the only analgesics with proven benefit in
severe pain. Rather than the current practice of slow dose
titration of one drug until effect or toxicity in all patients, the
emphasis should be towards ‘personalised medicine’ or
targeted therapy. Very little is known about the
pharmacokinetics/pharmacodynamics of opioids in patients
with cancer. The challenge is to determine which opioids are
best suited to each individual. This will require further re-
search into what factors determine the pharmacokinetic profile
of opioids in individual patients [99]. Genomics may play a
role, but to date, genetic variation has not been shown to have
major effect on response to opioid therapy.
Multimodal analgesia
Rather than relying solely on opioids for all painful condi-
tions, a combination of medications that work at different sites
or mechanisms of pain should be considered. Opioids can be
combined with anti-inflammatory medications, co-analgesics
and/or agents working through other receptors involved in
Support Care Cancer (2015) 23:1473–1481
pain transmission. This approach aims to minimise individual
drug doses and target multiple receptors [100].
Influence of pain duration
Some studies [101] have suggested that the longer a patient
experiences pain, the harder it is to achieve adequate analge-
sia. This may be related to the development of drug tolerance
or drug dependence. Future studies need to determine how
important timing of pain relief is as a predictive factor and
emphasises the need for early pain control.
A goal-orientated approach rather than a number/score-based
approach to pain management
To date, a response to pain has been measured numerically. It
is generally considered that a 2-point improvement on an 11-
point numerical rating scale constitutes a clinically relevant
improvement in pain [102]. Improving or maintaining an in-
dividual’s function and their achievement of daily goals may
be more important.
Increasing use of support services and the inter-disciplinary
team
Individualised inter-disciplinary palliative care is believed to
improve patient outcomes in cancer and end-of-life patients
[103]. Anecdotally, the ability of a patient or carer in distress
to be able to contact a health professional to discuss an issue or
problem can contribute significantly to symptom relief. Sev-
eral studies have shown the benefit of telephone support
[104]. Similarly, the involvement of an inter-disciplinary team
to provide holistic care may be the most effective means of
treating ‘total pain’ [105].
The development of standard definitions
The lack of international consensus for the classification and
assessment of pain for both research and clinical practice is
acknowledged and may contribute to failures in pain manage-
ment [106]. A generally accepted definition of refractory pain
is essential when assessing future treatment modalities.
Acknowledgment The authors wish to thank A/Prof John Hooper and
Prof CR Pinkerton for their advice and help in this project.
Funding BA was supported from a grant from the Mater Research
Institute.
Disclosures JH sits on the medical advisory boards of Mundipharma
Pty Ltd and Menarini Australia Pty Ltd. She has contributed to the opioid
educational modules of Mundipharma Pty Ltd.
Support Care Cancer (2015) 23:1473–1481
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