Wake up: Welcome and introduction Get a move on managing

Wake up:
Get a move on managing
fatigue in oncology patients
and recognizing the pharmacist’s role
April 23, 2017
Fairmont Banff Springs Hotel
Banff, Alberta
Welcome and introduction
Khristine Wilson, BSc PHM
Allan Blair Cancer Centre, Regina, Saskatchewan
1
Good morning!
Welcome to the Symposium
We look forward to a successful meeting with lots
of active discussion and participation
What brings us here today?
Describe the prevalence of fatigue in oncology patients and how it impacts
patient quality of life using a hormonal oral agent case example
•
•
Discuss exercise-based strategies to improve management of fatigue in
oncology patients
Review data on the impact of physical activity on patient quality of life
Recognize the role of pharmacists in counselling patients, monitoring fatigue,
and the importance of collaboration with other HCPs to optimize patient management
HCP, healthcare provider
2
Agenda
7:20 am
7:35 am
7:50 am
8:05 am
Questions and
discussion
Overview of oncologyrelated fatigue and impact
on quality of life
Exercise for the
management of
cancer-related fatigue
Pharmacists’ roles in
cancer-related fatigue
Naveen S. Basappa
Kerry S. Courneya
Khristine Wilson
Before we begin
Please save your questions for the Questions and discussion
session later this morning. Question cards have been provided
Please turn off all mobile devices
Please complete your evaluation form
3
Overview of oncology-related fatigue
and impact on quality of life
Naveen S. Basappa, MD FRCPC
Medical Oncologist
Cross Cancer Institute, Edmonton, Alberta
Disclaimer
Disclosures
 Sponsorship Support: Astellas, Janssen, Pfizer, Novartis
 Honorarium/Consulting Fees/Speaker Fees: Astellas, Janssen, Pfizer, Novartis,
BMS, AstraZeneca
Disclaimer
 The views and opinions that may be expressed by me in response to
questions/discussion are mine and mine alone, and should not be attributed to
Astellas Pharma Canada, its affiliates, or any of their respective directors,
officers, employees or contractors. Any opinions I may express in response to
questions/discussion regarding the unapproved use of a prescription product
and/or the use of an unapproved product will be identified as such and are
solely based on my clinical experience and medical judgment, and are in no way
intended to promote such unapproved use or unapproved product
4
What is fatigue?
Tiredness
Weariness
Weakness
Wiped Out
Low Energy
Exhaustion
Drained Lethargy
Worn Out Pooped
Tuckered Out
What is fatigue?
“Fatigue is a subjective feeling of
tiredness which is distinct from
weakness, and has a gradual onset.
Unlike weakness, fatigue can be
alleviated by periods of rest. Fatigue
can have physical or mental causes.”
Fatigue (medical). Wikipedia. 2017. https://en.wikipedia.org/wiki/Fatigue_(medical). Accessed: April 15, 2017.
5
What Is cancer-related fatigue?
(CRF)
“Cancer-related fatigue can be defined
as a distressing, persistent, subjective sense
of physical, emotional, and/or cognitive tiredness or
exhaustion related to cancer or cancer treatment
that is not proportional to recent activity and that
significantly interferes with usual functioning.”
Bower JE. Nat Rev Clin Oncol. 2014;11:597-609.
Prevalence of CRF
 Reported incidence:
 During therapy – 14–96% of patients1-7
 After therapy – 19–82% of patients8-10
Common and persistent
CRF, cancer-related fatigue
1. Fosså SD et al. J Clin Oncol. 2013;21:1249-54. 2. Miaskowski C et al. Principles and Practice of Supportive Oncology Updates. 1998;1:1-10. 3. Irvine DM et al. Cancer Nurs. 1991;14:188-99. 4. Vogelzang NJ et al. Semin Hematol. 1997;34:4-12.
5. Detmar SB et al. J Clin Oncol. 2000;18:3295-301. 6. Costantini M et al. Qual Life Res. 2000;9:151-9. 7. Cella D et al. Cancer. 2002;94:528-38. 8. Bower JE et al. Cancer. 2006;106:751-8. 9. Prue G et al. Eur J Cancer. 2006;42:846-63.
10. Orre IJ et al. J Psychosom Res. 2008;64:363-71.
6
Impact of CRF
 FATIGUE 11
 Affected performance of normal daily activities
is 2/3 of patients
 61% of patients said fatigue influenced
their life more than pain
 FATIGUE 22
 Fatigue main symptom after chemotherapy (25%)
 Effect on employment – 75% changed jobs
CRF, cancer-related fatigue
1. Vogelzang NJ et al. Int J Radiat Oncol Biol Phys 1997;34:4-12. 2. Curt GA et al. Proc Am Soc Clin Oncol 1999;18:573A.
Whose point of view?
Oncologist’s view
Patient’s view
Pain is more clinically relevant than
fatigue: 61% vs 37%
Fatigue affects everyday life more
than pain: 61% vs 19%
Stone P et al. Ann Oncol. 2000;11:971-5.
7
A complex web of CRF causes
Emotional
distress
Cancer itself
Sleep
problems
Cancer
treatments
Nausea &
vomiting
Causes of
CRF
Medications
Other
medical
Problems
Fatigue
before
treatment
Lack of
physical
activity &
exercise
Pain,
depression
or anxiety
Anemia
Nutrition
problems
low red blood
cell count
CRF, cancer-related fatigue
Adapted from: How to Manage Your Fatigue. Cancer Care Ontario. 2015. https://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=357461. Accessed: April 15, 2017.
Causes of fatigue
 Cancer and cancer treatment
 Changes in protein and hormone levels that are linked to inflammatory
processes which can cause or worsen fatigue
 Kill normal cells and cancer cells  build-up of cell waste. Extra energy
required to clean up and repair damaged tissue
 Formation of toxic substances in the body that change the way normal
cells work
 Paraneoplastic syndromes
 Nausea, vomiting, mucositis, diarrhea, constipation
8
Medical DDx for CRF
 Anemia
 Adrenal insufficiency
 Hypothyroidism
 Fever and/or infection
 Hormone levels
 Electrolytes, hepatic
or renal disorders
 Nutritional deficiencies
 Sleep disorders
 Mood disorders/depression
 Concomitant medications
 Comorbidities — particularly
in the elderly
 i.e. cardiovascular or pulmonary,
metabolic, endocrine, or liver
CRF, cancer-related fatigue; DDx, differential diagnosis
How should we screen for CRF?
 Screen for cancer fatigue severity using a valid quantitative or
semi-quantitative tool with established criteria for severity
 Mild = 1–3, Moderate = 4–6, Severe = >7
CRF, cancer-related fatigue
Watanabe SM et al. J Pain Symptom Manage. 2011;41:456-468. Selby D et al. J Pain Symptom Manage. 2010;39:241-249.
9
Mild Fatigue
Moderate Fatigue
• Minimal fatigue symptoms
• Able to carry out activities of daily living (ADLs) [self care,
homemaking, work, leisure]
• Symptoms present and cause moderate to high levels of
distress
• Decrease in daily physical activities, some impairment in
physical functioning
Severe Fatigue
• Significant fatigue on a daily basis, excessive need to sit or
sleep, severe impairment of ADLs
• Sudden onset of fatigue and/or shortness of breath at rest,
rapid heart rate and/or blood loss
Prevention and Supportive Care For All
Care Pathway 3
Urgent management of contributing factors,
Address safety issues (i.e. falls)
Care Pathway 2
Treat contributing factors
Care Pathway 1
Non-Pharmacological Interventions For Moderate To Severe Fatigue
• Advise patients to engage in moderate intensity of physical activity (e.g. fast walking, cycling, swimming, resistive exercise) during and after cancer treatment unless
contraindicated/previous sedentary (30 mins per day, 5 days per week as tolerated)
• Psychosocial interventions
• Psycho-education for self-management of fatigue (individual or group classes)
•
•
•
•
•
•
Anticipatory guidance about fatigue patterns
•
Energy balancing and coping skills training
•
Coaching in self-management and problem-solving to manage fatigue
• Refer for Cognitive Behavioural Therapy from trained therapist
• May experience improvement in fatigue from complementary therapies (yoga, mindfulness)
Consultation/referral to Rehabilitation Specialist if functioning impaired or need for supervised exercise
Optimize sleep quality (see sleep disturbance guidelines)
Stress reduction strategies may improve fatigue (yoga, mindfulness programs)
Attention restoring therapy may distract from fatigue (reading, games, music, gardening, experience in nature – Consensus)
Advise patient there is insufficient evidence for pharmacological treatment, herbal medicines, or acupuncture
Prevention and Supportive Care Interventions For All Patients & Caregivers, as appropriate
• EDUCATE
•
•
•
•
•
•
•
• COUNSEL
The difference between normal and cancer related fatigue
Treatment related fatigue patterns/fluctuations
Persistence of fatigue post treatment
Causes (contributing factors) of fatigue
Consequences of fatigue
Benefits of physical activity during and post treatment
Signs and symptoms of worsening fatigue to report to health care
professionals
• Balance energy conservation with activity as follows:
• Help patients prioritize and pace activities and delegate less
essential activities
• Balance rest and activities so that prioritized activities are
achieved
• ENCOURAGE USE OF TREATMENT LOG/DIARY
• To monitor levels and patterns of fatigue
• To help ascertain peak energy periods
• To help with planning activities
• Use of distraction such as games, music, reading, socializing
Evaluate Effectiveness of Interventions. Monitor Changes & Reassess As Required.
A pan Canadian practice guideline for screening, assessment, and management of cancer-related fatigue in adults. Canadian Partnership Against Cancer. 2015. https://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=362203.
Accessed: April 15, 2017.
Fatigue:
Metastatic castrationresistant prostate cancer
10
Management of mCRPC
 Primarily with androgen receptor-axis targeted therapy (ARAT)
 Enzalutamide 160 mg po daily
 Abiraterone plus prednisone 1000 mg po daily
 Highly efficacious hormonally targeted agents
 Primarily the 1st line treatment of choice
 Multiple improved endpoints including overall survival
mCRPC, metastatic castration-resistant prostate cancer, po, oral
Common Terminology Criteria For Adverse
Events (CTCAE v4.0): FATIGUE
Definition of fatigue: A
disorder characterized by a
state of general weakness with
a pronounced inability to
summon sufficient energy to
accomplish daily activities.
Grading
Description
1
Fatigue relieved by rest
2
Fatigue not relieved by rest; limiting
instrumental activities of daily living
3
Fatigue not relieved by rest, limiting
self-care activities of daily living
4/5
Not applicable
CTCAE Version 4.0. Retrieved March 5, 2015.
11
Trials on fatigue in mCRPC according to
National Cancer Institute toxicity criteria
Trial
Study Arms
Stage
Patient n
PS 0-1, %
Age
Hb, g/dL
Fatigue, %
G 3-4, %
Median OS,
Months
ENZ
Post-DOC
800
91
69
12.0
34
6
18.4
399
92
69
12.0
29
7
13.6
797
90
69
11.8
44
8
14.8
398
89
69
11.8
43
9
10.9
524
96
68
12.9
NR
18
22.6
526
95
69
12.6
NR
11
21.5
335
87
68
NR
53
5
18.9
DOCw with PDN
334
88
69
NR
49
5
17.4
MXN with PDN
337
86
68
NR
35
5
16.5
635
89
70
NR
18
1.9
14.3
315
89
68
NR
11
1.3
14.3
477
93
70
12.5
60
11
17.8
476
95
70
12.6
55
7
20.2
AFFIRM7
Placebo
ABI with PDN
Post-DOC
COU-AA-3015,27
Placebo with PDN
DP with BEV
MCRPC
CALGB-9040122
DP with Placebo
DOC with PDN
TAX 3273
STP with PDN
MCRPC
2nd line mCRPC
SPARC23
PDN
DOC with DN101
MCRPC
ASCENT24
DOC
ABI, abiraterone acetate; AFFIRM, A Study Evaluating the Efficacy and Safety of the Investigational Drug MDV3100; ASCENT, Androgen-Independent Prostate Cancer Study of Calcitriol Enhancing Taxotere; Asympt, asymptomatic; BEV,
bevacizumab; CALGB-90401, Cancer and Leukemia Group B CALGB-90401 (Alliance); DN101, high-dose calcitriol; DOC, docetaxel; DOCw, weekly docetaxel; DP, docetaxel with prednisone; ENZ, enzalutamide; G, Grade; Hb, hemoglobin;
mCRPC, metastatic castration-resistant prostate cancer; OS, overall survival; PDN, prednisone; PS, performance status; SIP, sipuleucel-T; SPARC, Satraplatin and Prednisone Against Refractory Cancer randomized phase III trial; STP, satraplatin
Colloca G et al. Clin Genitourin Cancer. 2016;14:5-11.
Trials on fatigue in mCRPC according to
National Cancer Institute toxicity criteria
Study
Drug
Fatigue (%)
Fatigue - Grade 3 (%)
PREVAIL
Enzalutamide
35.6
1.8
Placebo
25.8
1.9
Abiraterone + Prednisone
40
2
Prednisone
35
2
COUG-302
mCRPC, metastatic castration-resistant prostate cancer
1. Beer TM et al. Eur Urol. 2017;71:151-154. 2. Rathkopf DE et al. Eur Urol. 2014;66:815-25.
12
Fatigue is real…
 Fatigue is significant in mCRPC patients at baseline and
on treatment
 Numerically little difference in experimental arm vs standard arm
for fatigue with ARATs
 Although very well-tolerated, anecdotally fatigue is a commonly
reported adverse event with these therapies and in this
patient population
These drugs improve patients lives!
We must manage the toxicity!
ARAT, androgen receptor-axis targeted therapy; mCRPC, metastatic castration-resistant prostate cancer
Plan of action
 Screen for fatigue
 Address reversible physiological causes
 e.g. electrolytes, anemia, hypothyroidism
 Address psychosocial contributors
 Screen for depression, improve sleep habits
 Refer to Multidisciplinary Care Map
 Are there other interventions or resources that can help?
13
Mild Fatigue
Moderate Fatigue
• Minimal fatigue symptoms
• Able to carry out activities of daily living (ADLs) [self care,
homemaking, work, leisure]
• Symptoms present and cause moderate to high levels of
distress
• Decrease in daily physical activities, some impairment in
physical functioning
Severe Fatigue
• Significant fatigue on a daily basis, excessive need to sit or
sleep, severe impairment of ADLs
• Sudden onset of fatigue and/or shortness of breath at rest,
rapid heart rate and/or blood loss
Prevention and Supportive Care For All
Care Pathway 3
Urgent management of contributing factors,
Address safety issues (i.e. falls)
Care Pathway 2
Treat contributing factors
Care Pathway 1
Non-Pharmacological Interventions For Moderate To Severe Fatigue
• Advise patients to engage in moderate intensity of physical activity (e.g. fast walking, cycling, swimming, resistive exercise) during and after cancer treatment unless
contraindicated/previous sedentary (30 mins per day, 5 days per week as tolerated)
• Psychosocial interventions
• Psycho-education for self-management of fatigue (individual or group classes)
•
•
•
•
•
•
Anticipatory guidance about fatigue patterns
•
Energy balancing and coping skills training
•
Coaching in self-management and problem-solving to manage fatigue
• Refer for Cognitive Behavioural Therapy from trained therapist
• May experience improvement in fatigue from complementary therapies (yoga, mindfulness)
Consultation/referral to Rehabilitation Specialist if functioning impaired or need for supervised exercise
Optimize sleep quality (see sleep disturbance guidelines)
Stress reduction strategies may improve fatigue (yoga, mindfulness programs)
Attention restoring therapy may distract from fatigue (reading, games, music, gardening, experience in nature – Consensus)
Advise patient there is insufficient evidence for pharmacological treatment, herbal medicines, or acupuncture
Prevention and Supportive Care Interventions For All Patients & Caregivers, as appropriate
• EDUCATE
•
•
•
•
•
•
•
• COUNSEL
The difference between normal and cancer related fatigue
Treatment related fatigue patterns/fluctuations
Persistence of fatigue post treatment
Causes (contributing factors) of fatigue
Consequences of fatigue
Benefits of physical activity during and post treatment
Signs and symptoms of worsening fatigue to report to health care
professionals
• Balance energy conservation with activity as follows:
• Help patients prioritize and pace activities and delegate less
essential activities
• Balance rest and activities so that prioritized activities are
achieved
• ENCOURAGE USE OF TREATMENT LOG/DIARY
• To monitor levels and patterns of fatigue
• To help ascertain peak energy periods
• To help with planning activities
• Use of distraction such as games, music, reading, socializing
Evaluate Effectiveness of Interventions. Monitor Changes & Reassess As Required.
A pan Canadian practice guideline for screening, assessment, and management of cancer-related fatigue in adults. Canadian Partnership Against Cancer. 2015. https://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=362203.
Accessed: April 15, 2017.
FIN
14
Wake up:
Get a move on managing
fatigue in oncology patients
and recognizing the pharmacist’s role
April 23, 2017
Fairmont Banff Springs Hotel
Banff, Alberta
Exercise for the management of
cancer-related fatigue
Kerry S. Courneya, PhD
Professor and Canada Research Chair in Physical Activity and Cancer,
Faculty of Physical Education and Recreation,
University of Alberta, Edmonton, Alberta
15
Disclaimer
Disclosures
 Honorarium/Consulting Fees/Speaker Fees: Astellas
Disclaimer
 The views and opinions that may be expressed by me in response to
questions/discussion are mine and mine alone, and should not be attributed to
Astellas Pharma Canada, its affiliates, or any of their respective directors,
officers, employees or contractors. Any opinions I may express in response to
questions/discussion regarding the unapproved use of a prescription product
and/or the use of an unapproved product will be identified as such and are
solely based on my clinical experience and medical judgment, and are in no way
intended to promote such unapproved use or unapproved product
Exercise and Cancer-Related Fatigue (CRF)
 Exercise is a counterintuitive intervention
for CRF
 Cancer patients often advised to
“get plenty of rest”
 Exercise may be “tough medicine”
for CRF
 CRF is a common barrier to exercise
 Numerous systematic reviews and RCTs
have examined exercise for CRF
RCT, randomized controlled trial
16
Recent systematic review
Mustian KM et al. JAMA Oncol. 2017;doi:10.1001/jamaoncol.2016.6914
Recent systematic review
Exercise and psychological interventions improve CRF better than
pharmacological interventions
Intervention
No. of
effect sizes WES SE (95% CI)
All
127
0.33 0.05 (0.24-0.43)
Pharmaceutical
14
0.09 0.05 (0.00-0.19)
Exercise + psychological
10
0.26 0.07 (0.13-0.38)
Psychological
34
0.27 0.05 (0.21-0.33)
Exercise
69
0.30 0.03 (0.25-0.36)
More favourable
0.00
0.10
0.20
0.30
0.40
Overall WES
CI, confidence interval; CRF, cancer-related fatigue; SE, standard error; WES, Weighted Effect Size
Mustian KM et al. JAMA Oncol. 2017;doi:10.1001/jamaoncol.2016.6914
17
Exercise and prostate cancer patients
on oral therapy
 RCT examining the effects of RET
on QOL, fatigue, and muscular
strength in 155 prostate cancer
patients receiving ADT
 Dual centre study with Ottawa
and Edmonton
 Funded by NCIC/CPCRI
ADT, androgen deprivation therapy; CPCRI, Canadian Prostate Cancer Research Initiative; NCIC, National Cancer Institute of Canada; QOL, quality of life;
RCT, randomized controlled trial; RET, resistance training
Segal RJ et al. J Clin Oncol. 2003;21:1653-1659.
Change in upper body strength
Change in Standard load
test score (%)
60
p<0.001
50
40
30
20
10
0
-10
-20
UC
RET
RET, resistance training; UC, usual care
Segal RJ et al. J Clin Oncol. 2003;21:1653-1659.
18
Effect of RET on fatigue
Less fatigue
Change in FACT-F
questionnaire score
2
1
0
-1
-2
More fatigue
-3
Overall
Curative
UC
Palliative
RET
FACT-F, Functional Assessment of Cancer Therapy–Fatigue; QOL, quality of life; RET, resistance training; UC, usual care
Segal RJ et al. J Clin Oncol. 2003;21:1653-1659.
Prostate Radiotherapy and Exercise Versus
Normal Treatment (PREVENT) trial
 RCT comparing AET or RET
to UC on fatigue, QOL, and
physical fitness
 N=121 prostate cancer
patients receiving RT ± ADT
 Funded by NCIC/CPCRI
ADT, androgen deprivation therapy; AET, aerobic exercise training; CPCRI, Canadian Prostate Cancer Research Initiative; NCIC, National Cancer Institute of Canada; QOL, quality of life;
RCT, randomized controlled trial; RET, resistance training; UC, usual care
Segal RJ et al. J Clin Oncol. 2009;27:344-351.
19
Change in upper body strength
Change in 8-RM weight (%)
40
30
20
10
0
p<0.001
p<0.001
-10
-20
UC
AET
RET
8-RM, 8 repetition maximum; AET, aerobic exercise training; RET, resistance training; UC, usual care
Segal RJ et al. J Clin Oncol. 2009;27:344-351.
Change in aerobic fitness
5
Change in VO2peak (%)
4
3
2
1
p=0.030
p=0.054
0
-1
-2
-3
-4
-5
UC
AET
RET
AET, aerobic exercise training; RET, resistance training; UC, usual care; VO 2peak, peak volume of oxygen consumed
Segal RJ et al. J Clin Oncol. 2009;27:344-351.
20
Effect of exercise on fatigue
Less fatigue
3
Change in FACT-F
questionnaire score
2
1
0
-1
-2
-3
-4
-5
-6
More fatigue
-7
12 weeks
UC
AET
RET
24 weeks
AET, aerobic exercise training; FACT-F, Functional Assessment of Cancer Therapy–Fatigue; RET, resistance training; UC, usual care
Segal RJ et al. J Clin Oncol. 2009;27:344-351.
Model of exercise and CRF
Context
Participant: cancer type, gender, age, disease stage, comorbidities, treatment side effects
Fatigue state: mild, moderate, severe
PACC stage
Timing: pretreatment, treatment, survivorship, end of life
Intervention
Goal of exercise program: e.g. prevent, mitigate, or reduce CRF
Physiologic systems and energy system to be trained
Exercise prescription factors: mode, frequency, intensity, type and duration, exercise adherence
Environmental/social factors: supervised/self-directed, group/individual, location/setting, exercise personnel qualifications
Direct
Physiologic
Muscular strength,
muscular endurance,
cardiopulmonary fitness,
body composition
Fatigue outcome
Biologic/hematologic
Inflammatory response,
metabolic function,
(insulin resistance),
endocrine function,
immune function
Indirect
Psychological
Anxiety, depression,
distress, cognition
Behavioral
Sleep: quantity
and quality
Appetite
Social
Social interaction
Positive reinforcement
Change in hypothesized parameters
Effect on fatigue/components of fatigue
CRF, cancer-related fatigue; PACC, physical activity and cancer control
McNeely ML, Courneya KS. J Natl Compr Canc Netw. 2010;8:945-53
21
Segal R et al. Curr Oncol. 2017;24:40-46.
General exercise principles
 Avoid inactivity, as sedentary
behavior may be detrimental
 Some exercise is better than none
 More exercise is better
 Dose-response
 Start easy and progress slowly
 Exercise must be individualized
based on patient function,
side effects, and preferences
22
Exercise guidelines
Aim:
For 150 min/week of
moderate intensity
aerobic exercise
OR
75 min/week of
vigorous intensity
aerobic exercise
OR
An equivalent combination
that weights the vigorous
time twice as much
• e.g. 50% moderate and
50% vigorous exercise
2–3 days/week of strength exercises of major muscle groups
using 8–12 repetitions
Segal R et al. Curr Oncol. 2017;24:40-46.
What can pharmacists do?
Advocate for supervised exercise oncology programs at your center
(or exercise consultant)
Refer to supervised exercise programs where possible
• Consider rehabilitation programs and community-based programs
Recommend exercise to your patients
Provide written exercise materials to patients
Provide exercise prescription with drug prescription
23
Key points to remember
 Exercise is effective for improving CRF
 Evidence of mediation by physical fitness
 Resistance exercise appears helpful,
especially for prostate cancer patients
on ADT/RT
 CRF is a major barrier to exercise so
need to start low and progress slowly
 Pharmacists can recommend exercise
to patients
ADT, androgen deprivation therapy; CRF, cancer-related fatigue; RT, radiation therapy
1. Mustian KM et al. JAMA Oncol. 2017;doi:10.1001/jamaoncol.2016.6914. 2. Segal R et al. Curr Oncol. 2017;24:40-46.
Wake up:
Get a move on managing
fatigue in oncology patients
and recognizing the pharmacist’s role
April 23, 2017
Fairmont Banff Springs Hotel
Banff, Alberta
24
Pharmacists’ roles in
cancer-related fatigue
Khristine Wilson, BSc PHM
Allan Blair Cancer Centre, Regina, Saskatchewan
Disclaimer
Disclosures
 Grant/Sponsorship Support: N/A
 Honorarium/Consulting Fees/Speaker Fees: Astellas
Disclaimer
 The views and opinions that may be expressed by me in response to
questions/discussion are mine and mine alone, and should not be attributed to
Astellas Pharma Canada, its affiliates, or any of their respective directors,
officers, employees or contractors. Any opinions I may express in response to
questions/discussion regarding the unapproved use of a prescription product
and/or the use of an unapproved product will be identified as such and are
solely based on my clinical experience and medical judgment, and are in no way
intended to promote such unapproved use or unapproved product
25
A complex web of CRF causes
Emotional
distress
Cancer itself
Sleep
problems
Cancer
treatments
Nausea &
vomiting
Causes of
CRF
Medications
Other
medical
Problems
Fatigue
before
treatment
Pain,
depression
or anxiety
Anemia
Lack of
physical
activity &
exercise
low red blood
cell count
Nutrition
problems
CRF, cancer-related fatigue
Adapted from: How to Manage Your Fatigue. Cancer Care Ontario. 2015. https://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=357461. Accessed: April 15, 2017.
Modafinil
A non-amphetamine “wake-promoting” agent
Phase 3 RCT in patients with cancers of
varying histological origin1
N=631
Trial population:
Receiving RT ±
chemotherapy
Not recommended
for CRF*3
Phase 3 RCT in patients with metastatic
prostate or breast cancer2
Modafinil 200 mg/day
N=83
Modafinil 200 mg/day
Placebo
Trial population:
Receiving
docetaxel-based
chemotherapy
Placebo
• No improvement in patients with
mild to moderate fatigue
• Improvement in patients with severe
baseline fatigue (p=0.017)
• No statistically significant difference
in CRF
• Increase in toxicity, with patients
experiencing grade 2 or higher nausea
and vomiting in the modafinil arm
Modafinil can interact with enzalutamide and abiraterone
* According to the NCCN due to the limited number of studies and the marginal improvement in CRF
CRF, cancer-related fatigue; NCCN, National Comprehensive Cancer Network; RCT, randomized controlled trial; RT, radiation therapy
1. Jean-Pierre P et al. Cancer. 2010;116:3513-3520. 2. Hovey E et al. Support Care Cancer. 2014;22:1233-42.
3. NCCN Clinical Practice Guidelines in Oncology, Cancer-Related Fatigue Version 1.2017. NCCN. 2016. https://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed: April 15, 2017.
26
Corticosteroids
• Can be considered for patients at
the end of life2
• Glucocorticoid side effects limit
their long-term use
• Most helpful for patients with CRF
who are in the terminal phase of
cancer
Prednisone or Dexamethasone
RCT in patients with advanced cancers of
varying histological origin1
N=84
Trial population:
Receiving RT ±
chemotherapy
Dexamethasone 4 mg BID
Placebo
Limitations of trial
• Significant improvement of CRF at day
15 (p=0.008)
• Assessment of overall QOL showed
improvement at day 15 (p=0.03)
• Two week duration
• Long-term use of dexamethasone
is associated with long term side
effects
BID, twice-daily; CRF, cancer-related fatigue; NCCN, National Comprehensive Cancer Network; RCT, randomized controlled trial; RT, radiation therapy
1. Yennurajalingam S et al.. J Clin Oncol. 2013;31:3076-3082
2. NCCN Clinical Practice Guidelines in Oncology, Cancer-Related Fatigue Version 1.2017. NCCN. 2016. https://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed: April 15, 2017.
Methylphenidate
Psychostimulant with a short half-life and rapid onset of action
Phase 3 RCT in patients with cancers of
varying histological origin1
N=148
Trial population:
Receiving RT ±
chemotherapy
Meta-analysis of 5 RCTs in patients with
cancers of varying histological origin2
Methylphenidate 54 mg/day
N=426
Methylphenidate or
Dexamphetamine*
Placebo
Trial populations:
Trial population:
Receiving RT ±
chemotherapy
Placebo
• No difference in fatigue score
• Subset analysis suggested patients with
severe fatigue and/or advanced disease
had some improvement in fatigue
• Overall statistically significant benefit to
psychostimulants in alleviating fatigue vs.
placebo (p=0.005)
• 1 large study (n=152) had positive
results; the 4 other studies showed no
significant improvements in CRF scores
* Doses ranged from 5 mg OD to 10 mg BID
BID, twice-daily; CRF, cancer-related fatigue; NCCN, National Comprehensive Cancer Network; OD, once-daily; RCT, randomized controlled trial; RT, radiation therapy
1. Moraska AR et al. J Clin Oncol. 2010;28:3673-3679. 2. Minton O et al. J Pain Symptom Manage. 2010;41:761-767.
27
Methylphenidate
Psychostimulant with a short half-life and rapid onset of action
Phase 3 RCT in patients with cancers of
Side histological
effects include
varying
origin1
• Anxiety
Methylphenidate 54 mg/day
• N=148
Insomnia
• Loss
of appetite
Trial
population:
Receiving
RT ±
•chemotherapy
Headache
Placebo
• Nausea
• No difference in fatigue score
• Subset analysis suggested patients with
severe fatigue and/or advanced disease
had some improvement in fatigue
Meta-analysis of 5 RCTs in patients with
cancers of varying histological origin2
Caution:
N=426
Methylphenidate or
Dexamphetamine*
Trial populations:
Trial population:
Receiving RT ±
chemotherapy
Placebo
• No data after 8 weeks
of treatment
•
•
•
•
Meta-analysis was conducted on 5 RCTs (n=426)
Overall statistically significant benefit to psychostimulants in
alleviating fatigue vs. placebo (P=0.005)
1 large study (n= 152) had positive results; the 4 other
studies showed no significant improvements in fatigue
scores
Varying tumor types; included patients on and off chemo
* Doses ranged from 5 mg OD to 10 mg BID
BID, twice-daily; CRF, cancer-related fatigue; NCCN, National Comprehensive Cancer Network; OD, once-daily; RCT, randomized controlled trial; RT, radiation therapy
1. Moraska AR et al. J Clin Oncol. 2010;28:3673-3679. 2. Minton O et al. J Pain Symptom Manage. 2010;41:761-767.
Methylphenidate
NCCN, National Comprehensive Cancer Network
NCCN Clinical Practice Guidelines in Oncology, Cancer-Related Fatigue Version 1.2017. NCCN. 2016. https://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed: April 15, 2017
28
What herbs or supplements
can help manage CRF?
CRF, cancer-related fatigue
Coenzyme Q10
Antioxidant supplement with cardio-protective effects
RCT in patients with newly diagnosed breast cancer1
N=236
Coenzyme Q10 300 mg*
Trial population:
Receiving RT ±
chemotherapy
• No significant improvement in
self-reported fatigue between
coenzyme Q10 and placebo
at 24 weeks
Placebo
* Combined with 300 IU Vitamin E divided into 3 daily doses x 24 weeks
RCT, randomized controlled trial; RT, radiation therapy
Lesser GJ et al. J Support Oncol. 2013;11:31-42.
29
L-carnitine
Popular supplement for fatigue for its role in cellular energy metabolism
Phase 3 RCT in patients with cancers of
varying histological origin1
N=375
Trial population:
Receiving RT ±
chemotherapy
L-carnitine 2 g/day
• No statistically
significant difference
in fatigue (p=0.57)
Placebo
RCT, randomized controlled trial; RT, radiation therapy
Cruciani RA et al. J Clin Oncol. 2012;30:3864-3869.
Ginseng
Stimulant
Phase 3 RCT in patients with cancers of
varying histological origin1
N=364
Trial population:
Receiving RT ±
chemotherapy
Ginseng 2000 mg/day*
Placebo
• At 4 weeks improvement was not
statistically significant
• At 8 weeks statistically significant
improvement (p=0.003)
• Improvement was greatest in
patients undergoing active cancer
treatment vs patients who had
completed treatment
• Toxicities did not differ significantly
between arms
* Wisconsin ginseng
CRF, cancer-related fatigue; RCT, randomized controlled trial; RT, radiation therapy
1. Barton DL et al. JNCI. 2013;105:1230-1238.
2. NCCN Clinical Practice Guidelines in Oncology, Cancer-Related Fatigue Version 1.2017. NCCN. 2016. https://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed: April 15, 2017.
30
Ginseng
Stimulant
Phase 3 RCT in patients with cancers of
varying histological origin1
Additional confirmatory
studies
Ginseng 2000 mg/day*
N=364
are
needed before ginseng can
Trial population:
be widely
Receiving
RT ± recommended as a
chemotherapy
treatment for CRF1,2 Placebo
Potential for DIs2:
• At 4 weeks improvement was not
statistically significant
monoamine
oxidase
•• AtWarfarin,
8 weeks statistically
significant
inhibitors, (p=0.003)
calcium channel
improvement
• Improvement
was greatest in
blockers, cholesterol-lowering
patients
undergoing
active cancer
agents,
anti-platelets,
treatment vs patients who had
thrombolytic agents, diuretics,
completed treatment
and hormonal
agents
• Toxicities
did not differ
significantly
between
arms
• In vitro studies suggest that
ginseng inhibits CYP3A4
* Wisconsin ginseng
CRF, cancer-related fatigue; DI, drug interaction; RCT, randomized controlled trial; RT, radiation therapy
1. Barton DL et al. JNCI. 2013;105:1230-1238.
2. NCCN Clinical Practice Guidelines in Oncology, Cancer-Related Fatigue Version 1.2017. NCCN. 2016. https://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed: April 15, 2017.
Optimizing therapy of contributing factors
to fatigue
 Pain
 Emotional distress
 Depression
 Anxiety
 Anemia
 Sleep disturbance
 Nutritional deficits and imbalances
 Sodium, potassium, calcium, magnesium
 Nausea, vomiting, mucositis, diarrhea, constipation
CRF, cancer-related fatigue; NCCN, National Comprehensive Cancer Network
NCCN Clinical Practice Guidelines in Oncology, Cancer-Related Fatigue Version 1.2017. NCCN. 2016. https://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed: April 15, 2017
31
Medication management
 Reviewing current medications is essential
 Prescription, OTC, herbals, vitamins
 Drug interactions
 Recent medication changes should be noted
 Medications that can contribute to worsening fatigue





Beta blockers
Narcotics
Anti-emetics
Anti-depressants
Anti-histamines
 Polypharmacy
 Discontinue or adjust dose of medications if appropriate
 Alter dose or dosing interval
CRF, cancer-related fatigue; NCCN, National Comprehensive Cancer Network; OTC, over the counter
NCCN Clinical Practice Guidelines in Oncology, Cancer-Related Fatigue Version 1.2017. NCCN. 2016. https://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed: April 15, 2017
Monitoring fatigue
 Screen for fatigue at the initial counsel of new medications, dose changes,
and at routine follow-ups
 Document screening using a quantitative or semi-quantitative scale
 “How would you rate your fatigue on a scale of 0 to 10?”
 0 representing no fatigue and 10 the worst imaginable fatigue
Bower J et al. J Clin Oncol. 2014;32:1840-1850.
Oncology Nursing Society (2000).
32
Monitoring fatigue
 Encourage patients to self-monitor daily using a treatment log or
diary to help identify peak energy periods and the effectiveness of
specific interventions
 Record daily activities, time spent doing each activity, and how you
felt (e.g., fatigue level)
 Identify which activities were most tiring/difficult at the end of the day
 Plan for how these activities could be changed to make them
more manageable
Howes JL and Hamilton, J. Managing Your Cancer-Related Fatigue. Program of Care for Cancer, Nova Scotia Health Authority, Canadian Partnership Against Cancer, Halifax, Nova Scotia, December, 2016.
Counselling
 Education about fatigue should be offered to all patients with cancer,
especially those beginning potential fatigue-inducing treatments
 Chemotherapy, radiation therapy, hormone therapy
 Offer patients and their family information about the difference
between normal and CRF
 Ways to manage CRF
 Review causes and contributory factors
 Education about local support groups or online resources
CRF, cancer-related fatigue; NCCN, National Comprehensive Cancer Network
NCCN Clinical Practice Guidelines in Oncology, Cancer-Related Fatigue Version 1.2017. NCCN. 2016. https://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed: April 15, 2017
33
Helpful ways to manage fatigue
 Managing/conserving energy
 Managing stress and emotions
 Relaxation
 Distraction
 Sleep practices
 Healthy eating
 Physical activity
How to Manage Your Fatigue. Cancer Care Ontario. 2015. https://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=357461. Accessed: April 15, 2017.
The 4 P’s of managing your energy
1
2
3
4
Plan
Prioritize
Pace
Position
How to Manage Your Fatigue. Cancer Care Ontario. 2015. https://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=357461. Accessed: April 15, 2017.
34
Plan ahead
 Plan your activities during peak energy times
 Plan for rest periods before and after activities
 Plan activities or outings where you can sit down to rest
 Do one enjoyable activity everyday
 Do not do all of your difficult or tiring tasks on the
same day
 Delegate activities that are tiring or difficult to do
 Housework, shopping, pet care
 Arrange your home so that most activities can be
done on one floor
 Keep supplies within reach
How to Manage Your Fatigue. Cancer Care Ontario. 2015. https://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=357461. Accessed: April 15, 2017.
Prioritize
 Decide which activities are most
important to you
 Save your energy for things you
enjoy most
 Postpone less important activities
or ask others to do them for you
 Eliminate activities that you do not
have to do
How to Manage Your Fatigue. Cancer Care Ontario. 2015. https://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=357461. Accessed: April 15, 2017.
35
Pace
 Do one activity at a time
 Stop and rest before you get tired,
even if it means stopping in the
middle of a task
 Rest between activities
 Break tasks down into smaller steps
How to Manage Your Fatigue. Cancer Care Ontario. 2015. https://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=357461. Accessed: April 15, 2017.
Position
 If possible, sit when doing
things like folding laundry
or preparing food
 Use walking aids
 Hand rails, grab bars,
a cane, or a walker
 Avoid heavy lifting
How to Manage Cancer Related Fatigue [PDF]. (2017). Saskatchewan Cancer Agency.
36
Management of stress and emotions
 Focus on what is meaningful and important to you
 Try not to do too much
 Relaxation
 Deep breathing and relaxation exercises
 Guided imagery
 Meditation or clearing your mind
 Distraction
 Games, reading, listening to music
 Socializing with friends
Manage cancer related fatigue: For People Affected by Cancer. Canadian Partnership Against Cancer. 2015. https://content.cancerview.ca/download/cv/treatment_and_support/supportive_care/documents/managecancerfatiguepdf?attachment=0 .
Accessed April 15, 2017.
How to Manage Your Fatigue. Cancer Care Ontario. 2015. https://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=357461. Accessed: April 15, 2017.
Improve sleep habits
 Go to bed and get up at the same time
everyday
 Exercise regularly, even if it’s just a short walk
 Limit naps to less than 1 hour
 Avoid long or late afternoon naps
 Avoid drinking alcohol or caffeine in the
late afternoon or evening
 Limit activities and physical activity in
the evening
Manage cancer related fatigue: For People Affected by Cancer. Canadian Partnership Against Cancer. 2015. https://content.cancerview.ca/download/cv/treatment_and_support/supportive_care/documents/managecancerfatiguepdf?attachment=0 .
Accessed April 15, 2017.
How to Manage Your Fatigue. Cancer Care Ontario. 2015. https://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=357461. Accessed: April 15, 2017.
37
Eat Well
 Follow a balanced diet
 Stay hydrated
 Recommend 6 to 8 glasses of
fluid everyday
 If lack of appetite
 Eat small meals and healthy
snacks throughout the day
 Drink nutritional supplements with
meals or as a snack
 Consider a referral to see a
Registered Dietitian
Manage cancer related fatigue: For People Affected by Cancer. Canadian Partnership Against Cancer. 2015. https://content.cancerview.ca/download/cv/treatment_and_support/supportive_care/documents/managecancerfatiguepdf?attachment=0 .
Accessed April 15, 2017.
How to Manage Your Fatigue. Cancer Care Ontario. 2015. https://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=357461. Accessed: April 15, 2017.
EXERCISE!
Strongest evidence for
treating CRF
•
Encourage patients to get up and move even if it’s a short walk everyday
• Advocate and refer patients to local exercise programs if appropriate
CRF, cancer-related fatigue
38
Family and friends
 CRF can affect a patient’s family and friends
 Family/friends may feel:
 Helpless
 Anxious and worried about their loved one
 Loss/sadness because they cannot do the same activities with them
 Stressed
 Key: When counselling, it is important to acknowledge family and
friends and educate them about what to expect with CRF
 Offer suggestions on how they can help
CRF, cancer-related fatigue
Howes JL and Hamilton, J. Managing Your Cancer-Related Fatigue. Program of Care for Cancer, Nova Scotia Health Authority, Canadian Partnership Against Cancer, Halifax, Nova Scotia, December, 2016.
Resources for patients
 Cancer-related fatigue Mike Evans (10 min video)
 Accessible through Google
 Cancerconnection.ca
(Canadian Cancer Society)
 Cancerchatcanada.ca
 Cancerview.ca
 Cancer Care Ontario
 Saskatchewan Cancer Agency
 *Local programs at your Cancer Centre
39
Resources for patients
Cancer related fatigue mike evans. Youtube and google. 2017. https://www.google.ca/?gws_rd=ssl#q=cancer+related+fatigue+mike+evans&spf=377. Accessed: April 20, 2017
Resources for patients
Cancer connection. Canadian Cancer Society. 2017. www.cancerconnection.ca. Accessed: April 20, 2017
40
Resources for patients
Cancer chat. Cancer Chat Canada. 2017. www.cancerchatcanada.ca. Accessed: April 20, 2017
Resources for patients
How to manage your symptoms. Cancer Care Ontario. 2016. https://www.cancercare.on.ca/cms/one.aspx?objectId=347998&contextId=1377 Accessed: April 20, 2017
41
Resources for
patients
How to Manage Cancer-Related Fatigue.
Canadian Partnership Against Cancer. 2017.
http://www.saskcancer.ca/Cancer%20Related%20Fatigue%2002-2017. Accessed: April 20, 2017
Resources for patients
Living well with
cancer-related
fatigue video series
Cancer and Fatigue: Video Series. MyHealth.Alberta.ca. 2017. https://myhealth.alberta.ca/Alberta/cancer-fatigue. Accessed: April 20, 2017
42
Resources for patients
 Cancer-related fatigue Mike Evans (10 min video)
 Accessible through Google
 Cancerconnection.ca
(Canadian Cancer Society)
 Cancerchatcanada.ca
 Cancerview.ca
 Cancer Care Ontario
 Saskatchewan Cancer Agency
 *Local programs at your Cancer Centre
Collaboration with
other Health Care
Professionals
43
Referrals
 Physician
 Social Work
 Dietitian
 Rehabilitation
 Exercise therapy, occupational therapy
 Physically based therapies
 Massage therapy
 Psychosocial interventions
 Cognitive behavioral therapy (CBT)/behavioral therapy (BT)
National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Cancer-Related Fatigue Version 1.2017. 2016 December 19.
Key points to remember
 Pharmacologic and herbal medications have a limited role
in the treatment of CRF
 Exercise has the best evidence for reducing CRF and pharmacists
can recommend exercise for patients
 Pharmacists can play a key role in managing CRF for patients
 Identify patients experiencing CRF
 Manage contributing factors to CRF
 Provide counselling and resources
 Collaborate and provide referrals to appropriate HCPs
CRF, cancer-related fatigue; HCP, health care provider
44
THANK YOU
Wake up:
Get a move on managing
fatigue in oncology patients
and recognizing the pharmacist’s role
April 23, 2017
Fairmont Banff Springs Hotel
Banff, Alberta
45
Questions and
discussion
?
What did you think
of this morning’s
sessions?
Raise your hand
if you have any
questions
Please complete the
meeting evaluation form
Thank you for your
participation!
Your feedback is important to us
46
Wake up:
Get a move on managing
fatigue in oncology patients
and recognizing the pharmacist’s role
April 23, 2017
Fairmont Banff Springs Hotel
Banff, Alberta
47