Download Disclosure Objectives Objectives, continued

3/10/2016
Objectives
Cancer Survivorship and
the Role of Pharmacy
• Pharmacists:
– Describe the definition of cancer survivorship and
standards for survivorship care
– Discuss screening, assessment and management
of psychosocial and physical problems
experienced by cancer survivors
– Identify survivorship resources for health care
professionals and patients, and the role of
pharmacy in caring for cancer survivors
Katerine Dumais, PharmD, MPH
PGY-1 Pharmacy Practice Resident
Memorial Regional Hospital
www.fshp.org
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Disclosure
Objectives, continued
• Pharmacy Technicians:
• I do not have any conflicts of interest to
disclose in regards to the content of this
presentation
– Describe the definition of cancer survivorship
– Discuss late effects and long-term psychosocial
and physical problems experienced by cancer
survivors
– Identify the role of pharmacy in caring for cancer
survivors
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Survivorship Guidelines
Phases of Cancer Survivorship
Acute
Extended
Permanent
Diagnosis
Disease
stabilization
Remission
Selection of
treatment
Surveillance
Late side effects of
therapy
Fear and anxiety
Thoughts of
returning to normal
Long-term risks
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(Mullan F. N Engl J Med 313(4):270-3)
Definition
Survival Statistics
• Survivorship
• The number of people with a history of cancer
in the United States has increased
dramatically
– An individual is considered a cancer survivor from
the time of diagnosis, through the balance of his
or her life
– NOT limited to individuals who have no disease at
the completion of treatment
(National Comprehensive Cancer Network. Survivorship (Version 2.2015))
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– 3 million in 1971 to more than 14 million today
• About 64% of cancer survivors were
diagnosed with cancer five or more years ago
• More than half of cancer survivors are 65
years or older
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(American Society of Clinical Oncology. About Cancer Survivorship. http://www.cancer.net/survivorship/about-survivorship)
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Survival Statistics, continued
Challenges faced by Survivors
• Most common cancers among adult cancer
survivors:
• Cancer survivors
often face physical,
emotional, social
and financial
challenges as a result
of their diagnosis
and treatment
– 22% breast
– 20% prostate
– 9% colorectal
– 8% cervical, uterine or ovarian
(Image from www.campboggycreek.com)
(American Society of Clinical Oncology. About Cancer Survivorship. http://www.cancer.net/survivorship/about-survivorship)
Survival Statistics, continued
Standards for Survivorship Care
• Care of the cancer survivor should include:
• Incidence of childhood cancer has changed
only slightly since 1970
– Prevention of new and recurrent cancers and other late
effects
– Surveillance for cancer spread, recurrence, or second cancers
– Assessment of late psychosocial and physical effects
– Interventions for consequences of cancer and treatment (i.e.
medical problems, symptoms, psychological distress, financial
and social concerns)
– Coordination of care between primary care providers and
specialists to ensure that all of the survivors health needs are
met
– However, the overall survival rate for childhood
cancer has increased dramatically during this
period
• Overall survival rate for childhood cancer is
close to 80%
• Two-third of childhood cancer survivors have
at least one chronic health condition
(American Childhood Cancer Organization. http://www.acco.org/about-childhood-cancer/diagnosis/childhood-cancer-statistics/.)
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(National Comprehensive Cancer Network. Survivorship (Version 2.2015))
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Secondary Cancers
Long-term Effects of Specific Agents
• Genetic susceptibilities, shared causative
factors (smoking, obesity and environmental
exposure), and/or mutagenic effects of
previous cancer therapy increase risk
• Incidence differs based on caner type
– 2% in lymphoma survivors to 30% in survivors of
small cell lung cancer
• Expected to increase as cancer survivors live
longer
(National Comprehensive Cancer Network. Survivorship (Version 2.2015))
•
•
•
•
•
•
•
Pulmonary
fibrosis Bleomycin
Ototoxicity Platinums
Peripheral
NeuropathiesVinca
Alkaloids,
Platinums,
Taxanes
Cardiotoxicity Anthracyclines
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Psychosocial and Physical Effects
Anthracycline-Induced Cardiac Toxicity
Anthracycline-induced cardiac toxicity
Anxiety and Depression
Pain
Fatigue
Cognitive function
Sexual function
Sleep Disorders
• Anthracyclines (eg. doxorubicin, epirubicin,
daunorubicin) are used to treat many cancer types
(National Comprehensive Cancer Network. Survivorship (Version 2.2015))
– Breast cancer, lymphoma and sarcoma
• Reactive oxygen species (ROS) cause oxidative
injury, and the subsequent induction of apoptosis
in cancer cells
• Asymptomatic left ventricular ejection fraction
(LVEF) decline reported between 10 – 50 % in
various studies
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(National Comprehensive Cancer Network. Survivorship (Version 2.2015))
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Screening for Cardiac Toxicity
Anxiety and Depression
• All survivors should be
assessed for heart failure
within one year of
anthracycline therapy
• Additional risk factors
should be considered
– Other cardiotoxic
therapies, higher
cumulative dose (eg
cumulative dose of 300
mg/m2), underlying
cardiac issues
Vulnerability
Multiple
Stressors
Challenges
Anxiety
and
Depression
(Image from http://pharmacologycorner.com/drug-therapyheart-failure-ppt/)
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(National Comprehensive Cancer Network. Survivorship (Version 2.2015))
(National Comprehensive Cancer Network. Survivorship (Version 2.2015); Anderson BL, DeRubeis RJ, Berman BS, et al.. J Clin Oncol 32(18): 1605-1619)
Assessment and Management of
Cardiac Toxicity
Screening for Anxiety and Depression
Stage
Characteristics
Treatment
A
No structural disorder of the heart, but at risk for
developing heart failure:
• H/o cardiotoxic chemotherapy
• H/o chest irradiation
• Hypertension, coronary artery disease
diabetes mellitus
• H/o alcohol abuse, rheumatic fever
• Family h/o cardiomyopathy
•
•
•
• All patients with cancer should be evaluated for
symptoms of depression and anxiety at their initial
visit, at appropriate intervals and as clinically
indicated
Address underlying risk
factors: hypertension,
lipids, tobacco use,
obesity, metabolic
syndrome, diabetes
Recommend physical
activity and healthy diet
habits
Consider referral to
cardiologist
B
Structural heart disease but no signs or symptoms
of heart failure:
• Left ventricular hypertrophy
• Left ventricular dilation or hypocontractility
• Asymptomatic valvular disease
• Previous myocardial infarction
•
•
Measures under stage A
Referral to cardiologist
C
Signs and symptoms of heart failure
•
Referral to cardiologist
D
Advanced structural heart disease and marked
symptoms at rest despite maximal medical
therapy
•
Referral to cardiologist
(National Comprehensive Cancer Network. Survivorship (Version 2.2015))
– Post-treatment, recurrence, progression, transition to
palliative and end-of-life care
• Screening should be done using a valid and reliable
measure
– Nine-item Personal Health Questionnaire (PHQ-9),
Generalized Anxiety Disorder (GAD) 7-scale
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(National Comprehensive Cancer Network. Survivorship (Version 2.2015); Anderson BL, DeRubeis RJ, Berman BS, et al.. J Clin Oncol 32(18): 1605-1619)
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Assessment and Management of
Depression
Pharmacologic Interventions for
Anxiety and Depression
• First-line treatment:
– Selective serotonin reuptake inhibitors (SSRIs)
– Selective-norepinephrine reuptake inhibitors
(SNRIs)
– Benzodiazepines
PHQ-9
None/mild
(score 1-7)
Moderate
(score 8-14)
Moderate to
severe (score
15 –27)
Offer referral to
supportive
care services
Self-help;
Group based
therapy;
Physical activity;
Pharmacologic
Individual
based therapy;
Pharmacologic
(combined)
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(National Comprehensive Cancer Network. Survivorship (Version 2.2015); Anderson BL, DeRubeis RJ, Berman BS, et al.. J Clin Oncol 32(18): 1605-1619)
(National Comprehensive Cancer Network. Survivorship (Version 2.2015); Anderson BL, DeRubeis RJ, Berman BS, et al.. J Clin Oncol 32(18): 1605-1619)
Assessment and Management of
Anxiety
Pharmacologic Interventions for
Anxiety and Depression, continued
Concomitant Problems
GAD-7
None/mild
(score of 0-4,
5-9)
Moderate
(score 10-14)
Moderate to
severe
(score 15-21)
Offer referral to
supportive
care services
Self-help;
Group based
therapy;
Physical activity;
Pharmacologic
Individual
based therapy;
Pharmacologic
(combined)
Special Pharmacologic
Consideration
Substance Abuse
Minimize use of
benzodiazepines
Pain syndromes (eg,
neuropathy)
Serotonin-norepinephrine
reuptake inhibitors (SNRI)
Tricyclic antidepressants
Menopausal symptoms (eg, hot Gabapentin
flashes)
(300-600 mg/day),
Venlafaxine extended release
(37.5 -75 mg/day)
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(National Comprehensive Cancer Network. Survivorship (Version 2.2015); Anderson BL, DeRubeis RJ, Berman BS, et al.. J Clin Oncol 32(18): 1605-1619)
Fatigue
Bupropion
Insomnia
Mirtazapine,
Benzodiazepines
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(National Comprehensive Cancer Network. Survivorship (Version 2.2015); Anderson BL, DeRubeis RJ, Berman BS, et al.. J Clin Oncol 32(18): 1605-1619)
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Drug Interactions with Tamoxifen
Screening and Assessment of Pain
• All cancer survivors
should be screened for
pain at regular intervals
• Pain intensity should be
quantified by the
survivor
• Severe uncontrolled
pain is a medical
emergency
Paroxetine, Fluoxetine and Bupropion
Tamoxifen
Endoxifen
CYP2D6
(active form)
(Desmarias JE, Looper KJ. J Clin Psychiatry 70(12):1688-97)
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Pain
Management of Pain
• Goals are to increase comfort, maximize function and
improve quality of life
• Multidisciplinary approach is recommended
• More than one-third of cancer survivors
experience chronic pain
– Injury to somatic and visceral structures resulting
in nociceptive pain
– Neuropathic pain as a side-effect of chemotherapy
or radiation therapy or by surgical injury to the
nerves
– Pharmacologic, psychosocial interventions, physical
therapy and interventional procedures
• Management of eight distinct pain syndromes
addressed in the guidelines
– Neuropathic pain, chronic pain syndromes,
myalgias/arthralgias, skeletal pain, myofascial pain,
GI/urinary/pelvic pain, lymphedema, post-radiation pain
• Pain in survivors is often ineffectively
managed
(National Comprehensive Cancer Network. Survivorship (Version 2.2015))
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(National Comprehensive Cancer Network. Survivorship (Version 2.2015))
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(National Comprehensive Cancer Network. Survivorship (Version 2.2015))
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Duloxetine for the Management of
Neuropathic Pain
Management of Neuropathic Pain
General
measures
• Adjuvant analgesics
• Antidepressants
• Anticonvulsants
• Opioids
• Psychosocial interventions
• Consider hypnosis
Refractory
pain
• Pharmacologic therapies
• Topical patches
• Creams
• Non-pharmacologic therapies
• Heat, ice, acupuncture, etc.
(National Comprehensive Cancer Network. Survivorship (Version 2.2015))
• ASCO guideline only recommends duloxetine
for chemotherapy-induced peripheral
neuropathies (CIPN)
• Smith et al studied the effect of duloxetine in
a randomized, placebo-controlled trial of 231
patients with CIPN
– Patients receiving duloxetine reported a significant
decrease in pain compared with placebo (p = .003)
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Management of Neuropathic Pain,
continued
Agent
Tricyclic Antidepressants
(Nortriptyline and desipramine)
Dosing
Starting dose 20-30 mg daily
(increase to 60-10 mg daily)
Venlafaxine
Starting dose 37.5 mg daily
(increase to 75-225 mg daily)
Gabapentin
Starting dose 100-300 mg HS
(increase to 900-3600 mg daily
in 2-3 divided doses)
Pregabalin
Starting dose 50 mg TID
(increase to 100 mg TID)
(National Comprehensive Cancer Network. Survivorship (Version 2.2015))
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Fatigue
• Common complaint in individuals undergoing
chemotherapy
Start with a low dose and
increase every 3-5 days;
Starting dose 10-25 mg HS)
(increase to 50-150 mg HS)
Duloxetine
(Hershman DL, Lacchetti C, Dworkin RH, et al. J Clin Oncol 32(18): 1941-1967)
– May persist for months and years after cancer
diagnosis
• Important to assess for possible
comborbidities and/or medications
– Cardiac dysfunction, endocrine abnormalities
and/or anemia
– Sleep aids, pain medications and/or antiemetics
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(National Comprehensive Cancer Network. Survivorship (Version 2.2015))
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Fatigue Management
Patient/
Family
Education
Physical
Activity
Psychosocial;
Nutrition;
Sleep
Hygiene
Cancer Survivorship Guidelines
Pharmacologic
(National Comprehensive Cancer Network. Survivorship (Version 2.2015))
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Pharmacologic Agents for the
Management of Fatigue
Available at www.NCCN.org
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Cancer Survivorship Guidelines,
continued
• Evidence suggests that psycho-stimulants (eg,
methylphenidate) and other weakfulness
agents (eg, modafinil) can be effective in
patients with active disease
• Small pilot studies have evaluated
supplements, such as ginseng and vitamin D
– No consistent evidence of their effectiveness
ASCO has developed guidelines on prevention and management of
chemotherapy-induced peripheral neuropathy, fatigue, anxiety and
depression, and fertility preservation
(National Comprehensive Cancer Network. Survivorship (Version 2.2015); Bower JE, Bak K, Berger A, et al. Screening. J Clin Oncol 32(18): 1840-1850.
)
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Available at http://www.instituteforquality.org/practice-guidelines
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Cancer Survivorship at
Memorial Cancer Institute
Breast Cancer Survivorship Guidelines
Long-term Effect
Late Effect
Tamoxifen
Agent
Hot flashes
Changes in
menstruation
Mood changes
Increased triglycerides
Increased risk of stroke
Increased risk of
endometrial cancer
Increased risk of blood
clots
Osteopenia in
premenopausal
women
Aromatase inhibitors
Vaginal dryness
Decreased libido
Musculoskeletal pain
Cholesterol elevation
Increased risk of
osteoporosis
Increased risk of
fractures
Trastuzumab
Increased risk of
cardiac dysfunction
(Runowicz CD, Leach CR, Henry NL, et al.. J Clin Oncol. Published online before print December 7, 2015)
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Treatment Summary
and Survivorship Care Plan
Available at http://www.asco.org/practice-research/cancer-survivorship
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Chemotherapy Passport at
Memorial Cancer Institute
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Survivorship Resources
Role of Pharmacy
• “From a medication standpoint, a lot of cancer
therapies have lasting adverse effects—
neuropathy, heart failure, and so on. All of
those problems would be best managed by
pharmacists who can assess treatment
effectiveness and then work with patients to
optimize their regimens.”
- Daniel Zlott, PharmD, National Cancer
Institute
(National Comprehensive Cancer Network. Survivorship (Version 2.2015))
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Survivorship Resources, continued
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Role of Pharmacy, continued
• In the absence of a defined role for pharmacists
in cancer survivorship teams, we should use this
opportunity to create new possibilities for
pharmacists and pharmacy technicians to
optimize the care of cancer survivors
– Assisting patients in creating cancer treatment and
survivorship plans
– Monitoring and management of effects of cancer
diagnosis and treatment
– Preventing drug-drug interactions
(National Comprehensive Cancer Network. Survivorship (Version 2.2015))
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Assessment Question 1
Assessment Question 3
Which of the following anti-cancer agents is
associated with an increased risk of developing
heart failure?
A. Doxorubicin
B. Trastuzumab
C. Epirubicin
D. All of the above
Which agent has the most evidence for the
treatment of chemotherapy-induced peripheral
neuropathy.
A. Duloxetine
B. Nortriptyline
C. Gabapentin
D. All of these agents have similar evidence
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Assessment Question 2
Summary
A breast cancer survivor on tamoxifen has been
complaining of hot flashes. She was recently
diagnosed with depression. Which
antidepressant would you recommend?
A. Paroxetine
B. Fluoxetine
C. Bupropion
D. Venlafaxine
• The number of cancer survivors is increasing
• Cancer survivors face unique psychosocial and
physical effects
• There are resources available on cancer
survivorship for healthcare professionals
• We should create new possibilities for
pharmacists and pharmacy technicians to
optimize the care of cancer survivors
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Questions
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References
•
•
•
•
•
•
•
•
•
American Childhood Cancer Organization. Childhood Cancer Statistics. http://www.acco.org/aboutchildhood-cancer/diagnosis/childhood-cancer-statistics/. Accessed February 14, 216.
National Comprehensive Cancer Network. Survivorship (Version 2.2015).
Anderson BL, DeRubeis RJ, Berman BS, et al. Screening, Assessment, and Care of Anxiety and
Depressive Symptoms in Adults with Cancer: An American Society of Clinical Oncology Guideline
Adaptation. J Clin Oncol 32(18): 1605-1619.
Bower JE, Bak K, Berger A, et al. Screening, Assessment, and Care of Fatigue in Adults with Cancer: An
American Society of Clinical Oncology Guideline Adaptation. J Clin Oncol 32(18): 1840-1850.
Desmarais JE, Et al. Interactions between Tamoxifen and Antidepressants via Cytochrome P450 2D6. J
of Clin Psychiatry 70(12): 1688-97.
Hershman DL, Lacchetti C, Dworkin RH, et al. Prevention and Management of Chemotherapy-Induced
Peripheral Neuropathy in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical
Practice Guideline. J Clin Oncol 32(18): 1941-1967.
Runowicz CD, Leach CR, Henry NL, et al American Cancer Society/American Society of Clinical
Oncology Breast Cancer Survivorship Care Guideline. J Clin Oncol. Published online before print
December 7, 2015.
Mullan F. Seasons of survival: reflections of a physician with cancer. N Engl J Med 313(4):270-3.
American Society of Clinical Oncology. About Cancer Survivorship.
http://www.cancer.net/survivorship/about-survivorship. Accessed January 15, 2016.
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