BeCOn OWN Educational Program Modules. Module 4 Breakthrough cancer pain (BTcP) Date of preparation: June 2015 HQ/EFF/15/0024c

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)


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


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


Nociceptive NeuropathicMixed

The onset of BTcP is rapid, but variable


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


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


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


Algorithm for diagnosing patients with BTcP


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


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)


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)


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

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lges

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6

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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

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6am

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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


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


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


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


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

Documents

BeCOn OWN Educational Program Modules. Module 4 Breakthrough cancer pain (BTcP) Date of preparation: June 2015 HQ/EFF/15/0024c