BeCOn OWN Educational Program
Modules
Module 4Breakthrough cancer pain (BTcP)
Date of preparation: June 2015 HQ/EFF/15/0024c
Contents
Overview of BTcP
Management of BTcP
Overview of BTcP
Definition of breakthrough cancer pain (BTcP)
A transient exacerbation of pain that occurs either spontaneously, or in relation to a specific predictable or
unpredictable trigger, despite relatively stable and adequately controlled background pain
“ “
Davies A, et al. Eur J Pain. 2009;13(4):331-8.
The management of cancer-related breakthrough pain:
Recommendations of a task group of the Science Committee of the Association for Palliative Medicine of Great Britain and Ireland
Classification of BTcP
Spontaneous pain (idiopathic pain)
Episodes are not related to an identifiable precipitant, and so are unpredictable in nature
Incident pain (precipitated pain)
Episodes are related to an identifiable precipitant, and so are somewhat predictable.
Subclassified as:
– Volitional incident pain –brought on by a voluntary act (e.g. walking)
– Non-volitional incident pain –brought on by an involuntary act (e.g. coughing)
– Procedural pain –related to therapeutic intervention (e.g. wound dressing)
Davies A, et al. Eur J Pain. 2009;13(4):331-8.
Prevalence of BTcP
Pooled analysis of 19 observational studies
The overall pooled prevalence was 59.2%, with high heterogeneity
The lowest prevalence rates were detected in studies conducted in outpatient clinics (39.9%)
The highest prevalence was reported in studies conducted in hospice (80.5%)
Deandrea S, et al. J Pain Symptom Manage. 2014;47(1):57-76.
More than one in two patients with cancer pain also experiences BTcP
39.9%in outpatient clinics
80.5% in hospice
Narayana A, et al. Pain. 2015;156(2):252-9.
Interview of 2198 patients with opioid-treated chronic pain
80% of patients reported BTP
Patients had a median of 2.0 episodes of BTP per day (range, 1-50) and a median duration of BTP of 45 minutes (range, 1-720)
Compared with patients without BTP, patients with BTP had more pain-related interference in function, worse physical health and mental health, more disability and worse mood
BTP is highly prevalent and associated with negative outcomes.
National Breakthrough Pain Study
Characteristics of BTcP
Multicentre European study of BTcP in 320 patients
Median number of BTcP episodes3 perday
Median time to peak intensity10min
Median duration60min
Davies A, et al. J Pain Symptom Manage. 2013;46(5):619-28.
BTcP has many causes
Davies A, et al. Eur J Pain. 2009;13(4):331-8.
BTcP is not a single entity, but a spectrum of very different entities
BTcP is related to different causes
Cancer-related(e.g. inflammatory response,
nerve compression)
Treatment-related(e.g. radiation induced injury,
chemotherapy, surgery)
Concomitant illness
BTcP has different pathophysiologies
BTcP has complex pathophysiology
Davies A, et al. Eur J Pain. 2009;13(4):331-8.
Nociceptive NeuropathicMixed
The onset of BTcP is rapid, but variable
Davies A, et al. J Pain Symptom Manage. 2013;46(5):619-28.
Study of 1000 cancer patients from 13 European countries
Time to peak intensity of BTcP
Num
ber o
f pati
ents
(n=
936)
0
100
500
250
300
150
50
All BTcP Spontaneous BTcP Incident BTcP
400
0-5min
6-10min
11-15min
16-20min
21-25min
26-30min
31-40min
41-50min
>60min
461
159
234
11174
48 44 39 24 4024 14
131
62 51133 0 3 10 2
7234 27
450
350
200
51-60min
0 0 031
13 14
Median time to peak intensity is 10 minutes
The duration of BTcP is extremely heterogeneous
Davies A, et al. J Pain Symptom Manage. 2013;46(5):619-28.
Duration of untreated episodes
Study of 1000 cancer patients from 13 European countries
Num
ber o
f pati
ents
(n=
505)
0
40
140
80
100
60
20
All BTcP Spontaneous BTcP Incident BTcP
120
0-10min
11-20min
21-30min
31-60min
61-90min
91-120min
121-150min
151-180min
>180min
77
18
50
63 63
1929 28
23
115
68
37
144 8
73
33 31
87
0 0 0
46
33
135 6
The median duration for all BTcP was 60 min (range <1 min to 360 min)
BTcP: Italian Oncological Pain Survey (IOPS)
Italian survey of 1,412 cancer patients
Mean of 2.4 BTcP episodes/day
80.6% patients reported that BTcP had a significant negative impact on everyday life
The majority of patients reported a fast onset of BTcP, which was predictable in 50.7% of cases, while BTcP with a gradual onset (>10 min) was less predictable (29%)
Mean duration of background pain was 3.5 months before assessment
Mean duration of any analgesic treatment was 2.5 months before assessment
BTcP started a mean of 2.2 months before assessment
Patients in palliative care units were older, had lower Karnofsky levels, a lower number of BTcP episodes/day, a slower onset of BTcP onset and a less predictable BTcP
Mercadante S, et al. et al. Clin J Pain. 2015;31(3):214-21.
BTcP affects all areas of daily life
Davies A, et al. J Pain Symptom Manage. 2013;46(5):619-28.
Study of 1000 cancer patients from 13 European countries.
Interference with various aspects of daily living
Numerical rating (0-10)
Enjoyment of life
Relations with other people
Walking ability
Mood
0 2 3 4 5 6 7 8 9 10
Sleep
Normal work
General activity
1
2nd quartile 3rd quartile
BTcP has widespread implications
EONS. Breakthrough cancer pain guidelines 2013.Available at: http://www.cancernurse.eu/documents/EONSBreakthroughCancerPainGuidelines.pdf. Accessed 13 Apr 2015.
Depression
Walking
Working
Activities
BTcP
Increases
Reduces
Affects Affects
Anxiety Healthcare costs
Social relationship
Sleep
Quality of life Satisfaction with therapy
Management of BTcP
General considerations on management of breakthrough pain
Management involves:1. general assessment (e.g. pain assessment, explanation)
2. lifestyle changes (e.g. coping strategies)
3. management of reversible causes (e.g. incident pain precipitants)
4. modification of the pathological processes (e.g. antineoplastic therapies)
5. symptomatic management of BTcP (e.g. pharmacological and non-pharmacological)
6. reassessment (e.g. evaluation of pain and management)
The aim of breakthrough pain management is to reduce the intensity, severity,and impact of pain
Zeppetella G. Curr Opin Support Palliat Care. 2009;3(1):1-6.
Successful management is best achieved by thorough assessment, good communication, reassurance about pain relief and encouraging patient and carer participation
Non-pharmacological methods for management of breakthrough pain
A variety of non-pharmacological methods are used by patients, including:
Rubbing/massage
Application of heat
Application of cold
Distraction techniques
Relaxation techniques
However, there is relatively little evidence to support the use of these interventions in the treatment of breakthrough pain episodes
Davies A, et al. Eur J Pain. 2009;13(4):331-8.
Algorithm for diagnosing patients with BTcP
Davies A, et al. Eur J Pain. 2009;13(4):331-8.
Does the patient have background pain?Background pain = pain present
for >12 hour/day during previous week (or would be present if not taking analgesia)
Is the background pain adequately controlled?Adequately controlled = pain rated as “none”
or “mild”; but not “moderate” or “severe” for >12 hour/day during previous week
Patient does not have breakthrough pain, but does
have uncontrolledbackground pain
Does the patient have transientexacerbations of pain?
PATIENT HAS BREAKTHROUGH PAIN
YES
YES
YES
NO
NO PATIENT DOES NOT HAVE BREAKTHROUGH PAIN
NO
Onset of pain?
Frequency of pain?
Site of pain?
Radiation of pain
Quality (character) of pain?
Intensity (severity) of pain?
Duration of pain?
Exacerbating factors?
Relieving factors?
Response to analgesics?
Response to other interventions?
Associated symptoms?
Interference with activities of daily living?
More effective management of BTcP requires asking the right questions
Asking key questions can provide important insights into the patient’s pain
Davies A, et al. Eur J Pain. 2009;13(4):331-8.
An important consideration for adequate pain control in patients with cancer is appropriate and regular assessment of pain
The BAT comprises 14 questions
Measures 2 to 3 underlying pain dimensions based on analysis of generic cancer pain instruments
Queries BTcP frequency, intensity, duration and interference
The Breakthrough Pain Assessment Tool (BAT)
The BAT can facilitate the management of patients with breakthrough cancer pain in a clinical setting
Webber K, et al. J Pain Symptom Manage. 2014;48(4):619-31.
A fully validated clinical assessment tool for breakthrough pain in cancer patients
EONS: Management of BTcP
The aim of BTcP management is to reduce the intensity, severity and effect of each pain episode, and to lessen the impact of BTcP on patients’ quality of life.
The management of BTcP should be individualised, with the optimal approaches depending on:
Pain-related factors
– Aetiology of pain (cancer-related, treatment-related, concomitant illness)
– Pathophysiology of pain (nociceptive, neuropathic, mixed)
– Clinical features of pain
Patient-related factors
– Stage of the disease (early, advanced)
– Performance status of the patient (good, poor)
– Personal preferences of the patient
Breakthrough cancer pain guidelines 2013. European Oncology Nursing Society.Available at: http://www.cancernurse.eu/documents/EONSBreakthroughCancerPainGuidelines.pdf. Accessed 12 Mar 2015.
APM Recommendations
1. Patients with pain should be assessed for the presence of breakthrough pain (grade of recommendation: D)
2. Patients with breakthrough pain should have this pain specifically assessed (D)
3. The management of breakthrough pain should be individualised (D)
4. Consideration should be given to treatment of the underlying cause of the pain (D)
5. Consideration should be given to avoidance / treatment of the precipitating factors of the pain (D)
6. Consideration should be given to modification of the background analgesic regimen/“around the clock” medication (D)
Davies A, et al. Eur J Pain. 2009;13(4):331-8.
APM, Association of Palliative Medicine
APM Recommendations
7. Opioids are the “rescue medication” of choice in the management of breakthrough pain episodes (D)
8. The dose of opioid “rescue medication” should be determined by individual titration (B)
9. Non-opioid analgesics may be useful in the management of breakthrough pain episodes (D)
10.Non-pharmacological methods may be useful in the management of breakthrough pain episodes (D)
11. Interventional techniques may be useful in the management of breakthrough pain (D)
12.Patients with breakthrough pain should have this pain specifically re-assessed (D)
Davies A, et al. Eur J Pain. 2009;13(4):331-8.
APM, Association of Palliative Medicine
EONS: the ideal treatment for BTcP
The ideal treatment for most BTCP episodes is a rescue dose of a medication with the following features:
Effective (a strong opioid)
Pharmacokinetic properties that closely match the temporal characteristics of a BTcP episode, i.e. rapid onset with a relatively short duration of action
Patient-friendly – non-invasive, simple to administer
Minimal adverse effects
Cost-effective
Breakthrough cancer pain guidelines 2013. European Oncology Nursing Society. Available at: http://www.cancernurse.eu/documents/EONSBreakthroughCancerPainGuidelines.pdf. Accessed 12 Mar 2015.
Characteristics of immediate-release opioids used in BTcP
Bennett D, et al. P&T. 2005;30:354-361.
Immediate-release opioid
Onset of analgesia
Duration of effect
Advantages (A)/Disadvantages (D)
Morphine (oral) 30−40 min 4 hrA - available in multiple dosage forms, liquid concentrateD - slow onset of analgesia for idiopathic BTP
Oxycodone (oral) 30 min 4 hr Same as morphine
Hydromorphone (oral) 30 min 4 hrD - no liquid concentrate, slow onset of analgesia for idiopathic BTP
Methadone (oral) ~10−15 min 4−6 hrA - faster onset of analgesia in one small studyD - complex pharmacology, pharmacokinetics
Fentanyl (transmucosal) ~ 5−10 min 1−2 hrA - faster onset of analgesia D - requires ongoing patient cooperation in use
Hydrophilic
Lipophilic
Temporal relationship between BTcP episode and oral morphine treatment
A slow onset of action (analgesia: 20-30 min; peak analgesia: 60-90 min) results in delayed or ineffective analgesia, while the prolonged duration of effect (3-6 hr) results in ongoing adverse effects
Davies A, et al. Br J Nurs. 2011;20(13):803-4, 806-7.
Time (min)
Duration effect oral morphine
Peak effect oral morphine
Onset effect oral morphine
Duration of breakthrough pain
0 30 60 90 120 150 180 210 240 270
Treatment strategies for BTcP
BTcP has a time profile that is different from that of chronic persistent pain and should therefore be managed differently
Treatment of BTcP with oral immediate release opioids can take 30-45 minutes to produce an analgesic effect, which lasts for 3-6 hours
Control of background pain with the same, lower dose of an around-the-clock extended release opioid with BTcP managed using a transmucosal immediate-release fentanyl opioid minimises total opioid exposure while reducing BTcP
Simon SM, Schwartzberg LS. J Opioid Manag. 2014;10(3):207-15.
12amPa
in o
r ana
lges
ic in
tens
ity 10
8
6
4
0
9
7
5
3
12
3am
6am
9am
12pm
3pm
6pm
9pm
12am
3am
6am
9am
12pm
3pm
6pm
9pm
12am
ATC ER Opioid Alone
12amPain
or a
nalg
esic
inte
nsity 10
8
6
4
0
9
7
5
3
12
3am
6am
9am
12pm
3pm
6pm
9pm
12am
3am
6am
9am
12pm
3pm
6pm
9pm
12am
ATC ER Opioid + ROO
12amPa
in o
r ana
lges
ic in
tens
ity 10
8
6
4
0
9
7
5
3
12
3am
6am
9am
12pm
3pm
6pm
9pm
12am
3am
6am
9am
12pm
3pm
6pm
9pm
12am
ATC ER Opioid + IR Opioid
Simon SM, Schwartzberg LS. J Opioid Manag. 2014;10(3):207-15.
Several formulations of ROOs are available, which are characterised by a rapid onset of action (within minutes) and typically administered via a non-invasive transmucosal route
Lozenge Effervescent tablet Film
NASAL SPRAY
BUCCAL
Tablet Effervescent tablet Spray*
SUBLINGUAL
Currently available rapid-onset opioid formulations
*Not available in the EU.
Considerations for choice of rapid-onset opioids for management of BTcP
Factors to consider include individual patient characteristics, likelihood of adherence, characteristics of BTP and formulation preferences
Relevant patient attributes include lack of physical dexterity or weakness as it may make administration of oral transmucosal fentanyl citrate more difficult because it requires active patient participation
The presence of xerostomia may make some oral medications more difficult to administer
Mucositis may also influence the choice of an appropriate formulation, although most formulations are well tolerated in this situation
Smith HS. J Pain Res. 2013;6:189-200.
Evidence-based recommendations from the EAPC on use of opioids in BTcP
Recommendations for opioids in breakthrough pain
Strong recommendation that pain exacerbations from uncontrolled background pain should be treated with additional doses of immediate-release oral opioids
Appropriate titration of around-the-clock opioid therapy should always precede recourse to potent rescue opioid analgesics
BTcP can be effectively managed with oral, immediate-release opioids or buccal or intranasal fentanyl preparations
In some cases buccal or intranasal fentanyl preparations are preferable to immediate-release oral opioids because of more rapid onset of action and shorter duration of effect
Weak recommendation that immediate-release formulations of opioids with short half-lives should be used to treat pre-emptive predictable episodes of BTcP in the 20–30 min preceding the provoking manoeuvre
Caraceni A, et al. Lancet Oncol. 2012;13(2):e58-68.
EAPC, European Association for Palliative Care
ESMO: recommendations for BTcP
Immediate release oral morphine is appropriate to treat predictable episodes of BTP (i.e. pain on moving, on swallowing, etc.) when administered at least 20 min before such potential pain triggers (II A)
Intravenous opioids; buccal, sublingual and intranasal fentanyl drug delivery have a shorter onset of analgesic activity in treating BTP episodes in respect to oral morphine(I A)
Ripamonti I, et al. Ann Oncol. 2012;23 Suppl 7:vii139-54.
Meta-analysis of 10 RCTs
INFS, FPNS, FBT, and OTFC showed greater relative PIDs vs placebo than all other medications as early as 15 minutes post-baseline
With exception of MSIR, all medications were more efficacious vs placebo from 30 minutes post-baseline
Comparative efficacy of fentanyl buccal tablet
Zeppetella G, et al. J Pain Symptom Manage. 2014;47:772-85.
t (min): mean PID (95% Crl)
15: 1.68 (1.40; 1.96)30: 1.95 (1.63; 2.27)45: 1.95 (1.50; 2.39)60: 1.94 (1.47; 2.41)15: 0.56 (0.13; 0.99)30: 1.13 (0.56; 1.69)45: 1.30 (0.67; 1.92)60: 1.55 (0.88; 2.21)15: 0.53 (-0.03; 1.10)30: 0.83 (0.21; 1.46)45: 0.88 (0.40; 1.37)60: 0.93 (0.19; 1.68)15: 0.21 (-0.07; 0.48)30: 0.61 (0.26; 0.96)45: 0.71 (0.30; 1.12)60: 0.90 (0.47; 1.33)15: 0.51 (0.29; 0.73)30: 0.96 (0.62; 1.30)45: 1.41 (1.07; 1.76)60: 1.68 (1.30; 2.05)15: 0.46 (0.12; 0.81)30: 1.01 (0.57; 1.44)45: 1.32 (0.82; 1.82)60: 1.52 (0.95; 2.09)15: 0.12 (-0.35; 0.59)30: 0.51 (-0.13; 1.16)45: 0.83 (0.13; 1.53)60: 1.02 (0.23; 1.81)
IFNS, intranasal fentanyl spray; FPNS, fentanyl pectin nasal spray; FST, fentanyl sublingual Tablets; FBSF, fentanyl buccal soluble film; FBT, fentanyl buccal tablets; OTFC, oral transmucosal fentanyl citrate; MSIR, morphine sulphate immediate release
Favours placeboPID
Favours treatment
-3.0 -2.0 -1.0 0.0 1.0 2.0 3.0
INFS
FPNS
FST
FBSF
FBT
OTFC
MSIR
Opioids are the ‘‘rescue medication” of choice in management of BTcP
Davies A, et al. Eur J Pain. 2009;13(4):331-8.
The dose of opioid ‘‘rescue medication” should be determined by individual titration
Dose titration scheme for opioid ‘‘rescue medication”
Pain controlled/adverse effects
Pain not controlled/no adverse effects
Starting dose of opioid
Pain controlled/no adverse effects
Pain not controlled/adverse effects
Continue currentdose opioid
Decreasedose opioid
Increasedose opioid
Changetreatment
Adverse effects associated with opioids
Benyamin R, et al. Pain Physician 2008;11:S105-S120.
Adverse events
Common
Sedation
Dizziness
Nausea
Vomiting
Constipation
Physical dependence
Tolerance
Respiratory depression
Less common
Delayed gastric emptying
Hyperalgesia
Immunologic dysfunction
Hormonal dysfunction
Muscle rigidity
Myoclonus
Patients prefer an oral transmucosal route for relief of BTcP
Davies A, et al. Eur J Pain. 2011;15(7):756-63.
Multicentre European study of BTcP in 320 patients
Responses to questions about potential use of different routes of administration(‘‘would you consider using such a product?’’)
Num
ber o
f pati
ents
0
250
50
Oral transmucosal route Intranasal route Intrapulmonary route
150
Yes No Possibly Unfamiliarwith concept
200
100
Subcutaneous route
208
135 142
193
29
8270
58 67 77 7755
1626 31
14
Rapid-acting opioids are underused in management of BTcP
Simon SM, Schwartzberg LS. J Opioid Manag. 2014;10(3):207-15.Breuer B, et al. J Clin Oncol. 2011;29(36):4769-75.
The limitations in pain-related knowledge and practice within the oncology community have not been adequately addressed
only 10%
Despite the availabilityand utility of rapidly-acting
opioids
of oncologists identified this as a
recommendation theywould make
Implementing guidelines for BTcP
Preparation
Step 1: Set up a team
Step 2: Evaluate current practices
Step 3: Set objectives
Step 4: Prepare the way for implementation
Step 5: Plan the implementation process
Step 6: Get feedback on the tools
Implementation
Step 7: Implement the plan
Evaluation
Step 8: Evaluate the progress
EONS. Breakthrough cancer pain guidelines 2013.Available at: http://www.cancernurse.eu/documents/EONSBreakthroughCancerPainGuidelines.pdf. Accessed 13 Apr 2015.
The role of the nurse in treating BTcP
In the clinical and home-based settings, the nurse is one of the core professionals within a multidisciplinary team who is well positioned to identify problems and plan care accordingly
Oncology nurses have a key role to play in identifying, assessing, and managing BTcP, which should be conducted for each patient on an individual basis
Frequent contact with patients allows nurses to observe patients and actively communicate with them about their pain, potentially resulting in a more accurate diagnosis, better management of BTcP, and improved patient satisfaction with treatment
EONS. Breakthrough cancer pain guidelines 2013.Available at: http://www.cancernurse.eu/documents/EONSBreakthroughCancerPainGuidelines.pdf. Accessed 13 Apr 2015.
Nurses need adequate training to care for patients with BTcP
Rustøen T, et al. Eur J Oncol Nurs. 2013;17(1):95-100.
Patients do not receive the appropriate medical treatment for BTcP: nurses need better training about assessment and management of BTcP
Nur
ses
(%)
0
20
100
60
80
40
10
Unaware that medications
specifically intendedfor treatment of BTCP
exist
Reported that oral opioids were normally prescribed for BTCP at
their workplace
Did not use non-pharmacological
treatments for BTCP
Recommended positional change
90
70
50
30
38%
57%
38%
77%
Questionnaire-based survey of nurses (1241 completers) from 12 European countries who care for patients with cancer
Improving patient communication
Carers can play an active role in assessment and management of pain, but carer managed analgesia requires good communication with the clinician
Clinicians and nursing staff should get to know the patient and family as well as possible to enable patients and family to voice their fears, wishes and concerns with confidence
Scottish Intercollegiate Guidelines Network. Control of pain in adults with cancer.Available at: http://www.sign.ac.uk/pdf/SIGN106.pdf. Accessed 13 Mar 2015.
Patient input plays a major part in getting the most out of treatment: clinicians should encourage patients to report intensity, quality, location and pattern of pain
Key aspects of good communication
Good communication with patients and carers happens when:
– it is at their level of understanding
– is non-patronising
– free of jargon
– healthcare staff know the patient and carers well and actively listen
Poor communication between patients and professionals may result in clinical assessment that is not comprehensive, and under-reporting of pain by patients
Scottish Intercollegiate Guidelines Network. Control of pain in adults with cancer.Available at: http://www.sign.ac.uk/pdf/SIGN106.pdf. Accessed 13 Mar 2015.
Summary
BTcP can have many causes, and is experienced by about half of patients with cancer
BTcP has a negative impact on all aspects of quality of life
BTcP requires prompt diagnosis and treatment using defined algorithms
Opioids are the rescue medication of choice in management of BTcP
Improved communication with patients and among healthcare providers is essential in improving management of BTcP