How to Mitigate the LongTerm Effects of Treatment

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How to Mitigate the Long-Term 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

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The Changing Nature of Palliative Care
CURATIVE CARE
PALLIATIVE CARE
CURATIVE CARE
PALLIATIVE CARE
TIME
3
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

4
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

5
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

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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?
• Does 10 symptoms mean 10 medicines?
• Use of non-medical interventions
• Is an intervention to treat one symptom helping
  or hurting

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Changeable Nature of Patients Fears of
Chemotherapy

• Patients surveyed about symptom distress and
  fears prior to first ever cycle of chemo and then
  again prior to second cycle
• High levels of distress pretreatment
• Nausea and vomiting most feared pretreatment
• Drops to fifth most feared by second cycle

(Passik, Kirsh, et al, JPSM, 2001)
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Women with MBCa Have Many Choices

• Medical interventions
• Psychological interventions
• Alternative therapies
• Exercise and physical therapeutic interventions

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Pain
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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

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Monitoring Outcome The 4 As

• Analgesia (pain relief)
• Activities of Daily Living (psychosocial
  functioning)
• Adverse effects (side effects)
• Aberrant drug taking (addiction-related outcomes)
• (Passik and Weinreb, 1998)

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Communicating About Pain

• Communicate
• Intensity
• Location
• What the pain feels like
• What makes it worse
• What helps

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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

14
Future Developments in Pain

• Rapid onset opioids
• Oxymorphone
• Smart pills
• Alvimopan

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Depression
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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

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Diagnosing Depression in Cancer Patients

• Reliable Symptoms
• Anhedonia
• Persistent depressed mood
• Unreliable Symptoms
• Fatigue, insomnia, decreased libido, eating
  disturbances, situational emotional reactions

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Keys to Approaching Distress Programmatically
The SOS Program at MCC

• Screening program is essential
• Tailoring the program to your population
• Focus on the relevant symptoms distressing
  symptoms are different depending upon population
• Use the resources that you have
• Extend the reach of the mental health staff
  available
• Enfranchise the medical members of the team into
  the mental health effort
• Unify those who provide support to help with
  triage SOS program at Markey

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Management of Distress

• Following screening and triage, distress is
  managed with a hierarchical approach depending on
  severity
• Information, group support
• Crisis intervention and individual/family
  counseling approaches
• Medication management
• Combined medication and psychosocial treatments

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Recognizing Distress CCC 1994 Depression
Prevalence Survey
Study Results Level of Depression ZSDS (N /
) BZSDS (N/ ) None 711 (64.1) 764
(68.8) Mild 238 (21.5) 198
(17.9) Moderate 139 (12.5) 94 (
8.4) Severe 21 ( 1.9) 53 (
4.8) Total with depressive symptoms 398
(35.9) 345 (31.1) Correlation of BZSDS with
ZSDS r.92, plt.0001
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Patient-MD Concordance for Depression Ratings
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Patient-Nurse Concordance For Depression Ratings
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Prophylactic Work in Depression

• Testing a Strategy for Early Intervention and
  Prevention of Depression in Lung Cancer Patients
  Impact on Multiple Symptoms and Quality of Life
• (Passik, Kirsh, Mullett, Arnold, Leibee)
• Primary objective - determine if the use of an
  anti-depressant (mirtazapine) used to treat
  insomnia in patients being treated for lung
  cancer can be a useful prophylactic treatment for
  depression
• double-blind placebo controlled study
• half the patients receive 15 mgs. mirtazapine to
  take a bedtime
• half the patients will receive a placebo

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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

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Alternative Treatments for Depression

• Fish oil
• Exercise
• Yoga, meditation

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Nausea and Vomiting
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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)

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Olanzapine for the Relief of Opioid-Induced Nausea

• Cancer pain affects 15-90 ofcancer patients
• Nausea and vomiting affect approximately 40 of
  patients on opioids
• Consequences of opioid-induced nausea
• Impede adequate pain management
• Force changes in or refusal of treatment regimen
• Decrease psychosocial and physical functioning
• Diminish overall quality of life

(Passik, Lundberg, Kirsh, et al, JPSM, 2002)
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Potential of Olanzapine asAntiemetic 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)
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Alternative Treatments

• Relaxation
• The sacrificial lamb approach
• Wrist bands
• Acupuncture

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Maintaining Weight and Muscle Mass
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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)

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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)

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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)

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Future Work

• Interventions for Nutritional Risk in Radiation
  Patients
• (Passik, Kirsh, Huhn)
• Specific aims
• To examine the efficacy of nutritional counseling
  plus fish oil alone (NCFO) versus nutritional
  counseling plus fish oil plus olanzapine (NCFOO)
  in the treatment of nutritional risk in patients
  initiating radiation therapy.
• To compare the impact of NCFO vs. NCFOO on
  weight maintenance/gain, lean body mass,
  appetite, mood, nausea, body image, energy level,
  strength and overall quality of life in patients
  undergoing radiation therapy.

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Ongoing and Future Work

• Anabolic steroids
• Protein shakes
• Weight lifting with creatine
• Olanzapine

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Fatigue and Chemobrain
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Fatigue

• Highly prevalent effecting 2/3s of patients
• Very disabling
• Also makes the job of caregiving more stressful
  and exhausting for family

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Fatigue what works?

• Exercise
• Modifications in diet
• Stimulant medications

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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?

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Chemobrain What works?

• Stimulants
• Meditation?
• Anti-depressants?
• Medications that increase red blood cell counts
  (ie epo)?

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Insomnia and Hot Flashes
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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

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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)

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Hot Flashes

• Highly prevalent
• Vary tremendously in frequency and intensity from
  patient to patient
• Can be part of a viscious circle

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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

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www.cancer.gov

• Follow links to PDQ
• Supportive Care

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Conclusions

• 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