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How to Mitigate the LongTerm Effects of Treatment
Steven D. Passik, Ph.D.
Director, Symptom Management and
Pharmacotherapy Lab
Memorial Sloan Kettering Cancer Center
Department of Psychiatry and Behavioral Sciences
New York, NY
Cancer as a Disease
Experience



Survival rates increasing
Cancer has largely transformed from
an acute life threatening illness into
a chronic illness
Focus naturally being placed on
facilitating QOL
American Cancer Society, 1997, Sarafino, 1994
Goals of People With Cancer

Old days
• Get your affairs in order
• Comfort
• Say good-bye

Now-a-days
• Continue work, life interests, hobbies
• Maintain sense of self and identity
• Continue to play important family roles
But…

People with Cancer are Highly
Symptomatic
• Average in-pt has 10 distressing
symptoms
• Average out-pt has 5 distressing
symptoms with fatigue, GI upset and
pain leading the way
The Relationship of Symptoms to
Quality of Life

Chang and colleagues:
• Direct linear relationship between the
number of symptoms and patients’
reported quality of life

Symptom management is complex
• How to get the most bang for the buck?


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Does 10 symptoms mean 10 medicines?
Use of non-medical interventions
Is an intervention to treat one symptom
helping or hurting
Women with MBCa Have Many
Choices




Medical interventions
Psychological interventions
Alternative therapies
Exercise and physical therapeutic
interventions
Pain
Pain Statistics



Cancer pain is common but not inevitable
Fatigue, GI upset, and psychosocial
problems are often more prevalent, but
pain is the #1 feared aspect of cancer for
most patients
Rates of pain vary widely among disease
sites:
• 35% in lymphoma
• 56% in breast cancer
• 67% in head and neck cancer
Communicating About Pain

Communicate
• Intensity
• Location
• What the pain feels like
• What makes it worse
• What helps
What Not to Fear



Addiction
Tolerance (using meds too soon, i.e.,
before “I really need them”)
Side effects
• Good treatments exist for nausea,
sedation and a ground breaking
treatment will soon be available for
constipation
Future Developments in Pain




Rapid onset opioids
Oxymorphone
“Smart” pills
Alvimopan
Depression
Depression: Background




Depressive spectrum: normal
unhappiness, adjustment disorder, major
depression
Diagnosis often complicated by somatic
symptoms of cancer and its treatment
Psychotherapeutic, problem solving
approaches have been well-validated
Growing body of research on
antidepressants
Diagnosing Depression in Cancer
Patients
o
Reliable Symptoms
o Anhedonia
o Persistent depressed mood
o
Unreliable Symptoms
o Fatigue, insomnia, decreased libido,
eating disturbances, situational
emotional reactions
Patient-MD Concordance for
Depression Ratings
PATIENT
NONE
MILD
MOD./
Severe
TOTAL
PHYSICIAN
No.
%
No.
%
No.
%
No.
%
None
560
79
145
61
78
49
783
70.9
Mild
131
18
77
33
61
38
269
24.3
Moderate/
Severe
18
3
15
6
20
13
53
4.8
Total
709
64.2
237
21.4
159
14.4
Patient-Nurse Concordance
For Depression Ratings
PATIENT
NONE
MILD
MOD./
Severe
TOTAL
NURSE
No.
%
No.
%
No.
%
No.
%
None
576
81
146
61
84
53
806
72.9
Mild
107
15
69
29
52
33
228
20.6
Moderate/
Severe
26
4
23
10
23
14
72
6.5
Total
709
64.2
238
21.4
159
14.4
Antidepressant Selection



The art of treating depression
pharmacologically
Minimization vs. Mobilization – match to
symptom complex
The oncologist should learn to use 3 drugs
alone or in combination:
• “Clean” (one SSRI: fluoxetine, paroxetine,
sertraline, venlafaxine)
• “Dirty” (mirtazapine)
• Stimulant (methlyphenidate)

If the patient fails to respond or has
significant existential issues --- Refer to a
psycho-oncologist
Alternative Treatments for
Depression



Fish oil
Exercise
Yoga, meditation
Nausea and Vomiting
Etiologies of Nausea and Vomiting
in Oncology Patients

Chemical (chemotherapy-induced: acute
and delayed; opioids)

Vestibular

CNS (increased intracranial pressure)

Visceral (direct disease-related sources,
abdominal irradiation)
Potential of Olanzapine as
Antiemetic Therapy


Literature indicates the need for activity at
multiple receptor sites to control opioid-induced
nausea and vomiting (which arises from visceral,
vestibular, and CNS etiologies)
Olanzapine has activity at multiple receptor sites
•
•
•
•
•

Dopaminergic (D1, D2, D3, D4)
Serotonergic (5-HT2A, 5-HT2C, 5-HT6, 5-HT3)
Adrenergic (1)
Histaminergic (H1)
Muscarinic (m1, m2, m3, m4)
Minimal extrapyramidal side effects (EPS)
(Passik, Lundberg, Kirsh, et al, JPSM, 2002)
Alternative Treatments



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Relaxation
The sacrificial lamb approach
Wrist bands
Acupuncture
Maintaining Weight and Muscle
Mass
Cachexia and Nutritional Risk

Nutritional risk (ie, unwanted weight loss),
including cachexia, is a common and distressing
problem in advanced cancer, affecting up to 80%
of patients (Bruera, 1993)

Negatively affects survival as well as quality of
life (Delmore, 1993)

Etiologies:
• abnormal gastrointestinal functioning
• anorexia from nausea, anxiety, depression and cognitive
dysfunction
• metabolic abnormalities caused principally by cytokines
(Keller, 1993)
Cachexia and Nutritional Risk

4 main clinical manifestations of cachexia:
•
•
•
•

Anorexia
Chronic nausea
Asthenia
Change in body image
Pharmacologic treatment of cachexia is
targeted principally at anorexia and
chronic nausea (Bruera, 1993)
Pharmacological Approaches

The main pharmacologic approaches include:
•
•
•
•
•
•
Corticosteroids
Progestational agents (ie, megestrol acetate)
Cannabinoids (ie, dronabinol)
Antihistamines (ie, cyproheptadine)
Unique agents (ie, hydrazine sulfate)
Omega-3 fatty acids, EPA and docosahexaneoic acid
(DHA) (n-3s) (Barber, et al, 2000; Hussey & Tisdale, 1999;
Wigmore, et al, 2000)

Results of trials for cachexia have been mixed
(Bruera, et al, 1985; Gold, 1975; Lener & Regelson, 1976; Silverstein, et
al, 1989; Tayek, et al, 1987; Wadleigh, et al, 1990)
Ongoing and Future Work


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Anabolic steroids
Protein shakes
Weight lifting with creatine
Olanzapine
Fatigue and Chemobrain
Fatigue


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Highly prevalent – effecting 2/3s of
patients
Very disabling
Also makes the job of caregiving
more stressful and exhausting for
family
Fatigue – what works?


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Exercise
Modifications in diet
Stimulant medications
Chemobrain

What really is chemobrain?
• Subjective sense of slowed thinking,
muddy thinking, lack of flexibility in
cognitive processes
• Poor concentration and secondarily, poor
memory

What causes it?
• Chemo? Hormones? Other meds?
Chemobrain – What works?


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Stimulants
Meditation?
Anti-depressants?
Medications that increase red blood
cell counts (ie epo)?
Insomnia and Hot
Flashes
Insomnia

Highly prevalent symptom
• 53% of people with cancer report
difficulty sleeping
• Breast cancer

Multiple problems can lead to poor sleep
• Pain
• Hot flashes
• Worry
Insomnia

Multiple new sleep aids on the
market
• Eszopiclone
• Remelteon


None evaluated in people with cancer
An oldie but a goodie
• Trazadone (only hot flas med that is
sedating and can be taken at bedtime)
Hot Flashes

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
Highly prevalent
Vary tremendously in frequency and
intensity from patient to patient
Can be part of a viscious circle
Hot Flashes

Antidepressants work best
•
•
•
•

SNRIs (venlafaxine and possibly duloxetine)
SSRIs
Others?
Olanzapine (?)
Most of the herbal and supplement based
treatments in effective
• Loprinzi latest was negative trial of black
cohosh
www.cancer.gov
Follow links to PDQ
Supportive Care
Conclusions



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
People with cancer are living longer
The focus is on quality of life in addition to
quantity
People surviving cancer want to live
normal lives
People with cancer have multiple
symptoms
New treatments of various kinds are
available and there is no need to suffer
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