How to Mitigate the Long-How to Mitigate the Long-Term Effects of TreatmentTerm Effects of Treatment

Steven D. Passik, Ph.D.Director, Symptom Management and

Pharmacotherapy LabMemorial Sloan Kettering Cancer Center

Department of Psychiatry and Behavioral SciencesNew York, NY

Cancer as a Disease Cancer as a Disease ExperienceExperience

Survival rates increasingSurvival rates increasing

Cancer has largely transformed from Cancer has largely transformed from an an acuteacute life threatening illness into life threatening illness into a a chronicchronic illness illness

Focus naturally being placed on Focus naturally being placed on facilitating QOL facilitating QOL

American Cancer Society, 1997, Sarafino, 1994American Cancer Society, 1997, Sarafino, 1994

Goals of People With CancerGoals of People With Cancer

Old daysOld days• Get your affairs in orderGet your affairs in order• ComfortComfort• Say good-byeSay good-bye

Now-a-daysNow-a-days• Continue work, life interests, hobbiesContinue work, life interests, hobbies• Maintain sense of self and identityMaintain sense of self and identity• Continue to play important family rolesContinue to play important family roles

But…But…

People with Cancer are Highly People with Cancer are Highly SymptomaticSymptomatic• Average in-pt has 10 distressing Average in-pt has 10 distressing

symptomssymptoms• Average out-pt has 5 distressing Average out-pt has 5 distressing

symptoms with fatigue, GI upset and symptoms with fatigue, GI upset and pain leading the waypain leading the way

The Relationship of Symptoms to The Relationship of Symptoms to Quality of LifeQuality of Life

Chang and colleagues:Chang and colleagues:• Direct linear relationship between the Direct linear relationship between the

number of symptoms and patients’ number of symptoms and patients’ reported quality of lifereported quality of life

Symptom management is complexSymptom management is complex• How to get the most bang for the buck? How to get the most bang for the buck?

Does 10 symptoms mean 10 medicines?Does 10 symptoms mean 10 medicines? Use of non-medical interventionsUse of non-medical interventions Is an intervention to treat one symptom Is an intervention to treat one symptom

helping or hurtinghelping or hurting

Women with MBCa Have Many Women with MBCa Have Many Choices Choices

Medical interventionsMedical interventions Psychological interventionsPsychological interventions Alternative therapiesAlternative therapies Exercise and physical therapeutic Exercise and physical therapeutic

interventionsinterventions

PainPain

Pain StatisticsPain Statistics Cancer pain is common but not inevitableCancer pain is common but not inevitable

Fatigue, GI upset, and psychosocial Fatigue, GI upset, and psychosocial problems are often more prevalent, but problems are often more prevalent, but pain is the #1 feared aspect of cancer for pain is the #1 feared aspect of cancer for most patientsmost patients

Rates of pain vary widely among disease Rates of pain vary widely among disease sites:sites:• 35% in lymphoma35% in lymphoma• 56% in breast cancer56% in breast cancer• 67% in head and neck cancer67% in head and neck cancer

Communicating About PainCommunicating About Pain

CommunicateCommunicate• IntensityIntensity• LocationLocation• What the pain feels likeWhat the pain feels like• What makes it worse What makes it worse • What helpsWhat helps

What Not to FearWhat Not to Fear

AddictionAddiction Tolerance (using meds too soon, i.e., Tolerance (using meds too soon, i.e.,

before “I really need them”)before “I really need them”) Side effectsSide effects

• Good treatments exist for nausea, Good treatments exist for nausea, sedation and a ground breaking sedation and a ground breaking treatment will soon be available for treatment will soon be available for constipationconstipation

Future Developments in PainFuture Developments in Pain

Rapid onset opioidsRapid onset opioids OxymorphoneOxymorphone ““Smart” pillsSmart” pills AlvimopanAlvimopan

DepressionDepression

Depression: BackgroundDepression: Background Depressive spectrum: normal unhappiness, Depressive spectrum: normal unhappiness,

adjustment disorder, major depressionadjustment disorder, major depression

Diagnosis often complicated by somatic Diagnosis often complicated by somatic symptoms of cancer and its treatmentsymptoms of cancer and its treatment

Psychotherapeutic, problem solving Psychotherapeutic, problem solving approaches have been well-validatedapproaches have been well-validated

Growing body of research on Growing body of research on antidepressantsantidepressants

Diagnosing Depression in Cancer Diagnosing Depression in Cancer PatientsPatients

o Reliable SymptomsReliable Symptomso AnhedoniaAnhedoniao Persistent depressed moodPersistent depressed mood

o Unreliable SymptomsUnreliable Symptomso Fatigue, insomnia, decreased libido, Fatigue, insomnia, decreased libido,

eating disturbances, situational eating disturbances, situational emotional reactionsemotional reactions

Patient-MD Concordance for Patient-MD Concordance for Depression RatingsDepression Ratings

PATIENT

NONE MILDMOD./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 Patient-Nurse Concordance For Depression RatingsFor Depression Ratings

PATIENT

NONE MILDMOD./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 SelectionAntidepressant Selection The art of treating depression The art of treating depression

pharmacologicallypharmacologically Minimization vs. Mobilization – match to Minimization vs. Mobilization – match to

symptom complexsymptom complex The oncologist should learn to use 3 drugs The oncologist should learn to use 3 drugs

alone or in combination:alone or in combination:• ““Clean” (one SSRI: fluoxetine, paroxetine, Clean” (one SSRI: fluoxetine, paroxetine,

sertraline, venlafaxine)sertraline, venlafaxine)• ““Dirty” (mirtazapine)Dirty” (mirtazapine)• Stimulant (methlyphenidate)Stimulant (methlyphenidate)

If the patient fails to respond or has significant If the patient fails to respond or has significant existential issues --- Refer to a psycho-oncologistexistential issues --- Refer to a psycho-oncologist

Alternative Treatments for Alternative Treatments for DepressionDepression

Fish oilFish oil ExerciseExercise Yoga, meditationYoga, meditation

Nausea and VomitingNausea and Vomiting

Etiologies of Nausea and Vomiting Etiologies of Nausea and Vomiting in Oncology Patientsin Oncology Patients

Chemical (chemotherapy-induced: acute Chemical (chemotherapy-induced: acute and delayed; opioids)and delayed; opioids)

VestibularVestibular

CNS (increased intracranial pressure)CNS (increased intracranial pressure)

Visceral (direct disease-related sources, Visceral (direct disease-related sources, abdominal irradiation)abdominal irradiation)

Potential of Olanzapine asPotential of Olanzapine asAntiemetic TherapyAntiemetic Therapy

Literature indicates the need for activity at Literature indicates the need for activity at multiple receptor sites to control opioid-induced multiple receptor sites to control opioid-induced nausea and vomiting (which arises from visceral, nausea and vomiting (which arises from visceral, vestibular, and CNS etiologies)vestibular, and CNS etiologies)

Olanzapine has activity at multiple receptor sitesOlanzapine has activity at multiple receptor sites• Dopaminergic (D1, D2, D3, D4)Dopaminergic (D1, D2, D3, D4)• Serotonergic (5-HT2A, 5-HT2C, 5-HT6, 5-HT3)Serotonergic (5-HT2A, 5-HT2C, 5-HT6, 5-HT3)• Adrenergic (Adrenergic (1)1)• Histaminergic (H1)Histaminergic (H1)• Muscarinic (m1, m2, m3, m4)Muscarinic (m1, m2, m3, m4)

Minimal extrapyramidal side effects (EPS)Minimal extrapyramidal side effects (EPS)(Passik, Lundberg, Kirsh, et al, JPSM, 2002)

Alternative TreatmentsAlternative Treatments

RelaxationRelaxation The sacrificial lamb approachThe sacrificial lamb approach Wrist bandsWrist bands AcupunctureAcupuncture

Maintaining Weight and Muscle Maintaining Weight and Muscle MassMass

Cachexia and Nutritional RiskCachexia and Nutritional Risk Nutritional risk (ie, unwanted weight loss), Nutritional risk (ie, unwanted weight loss),

including cachexia, is a common and distressing including cachexia, is a common and distressing problem in advanced cancer, affecting up to 80% problem in advanced cancer, affecting up to 80% of patients of patients (Bruera, 1993)(Bruera, 1993)

Negatively affects survival as well as quality of Negatively affects survival as well as quality of life life (Delmore, 1993)(Delmore, 1993)

EtiologiesEtiologies: : • abnormal gastrointestinal functioningabnormal gastrointestinal functioning• anorexia from nausea, anxiety, depression and cognitive anorexia from nausea, anxiety, depression and cognitive

dysfunctiondysfunction• metabolic abnormalities caused principally by cytokinesmetabolic abnormalities caused principally by cytokines(Keller, 1993)(Keller, 1993)

Cachexia and Nutritional RiskCachexia and Nutritional Risk

4 main clinical manifestations of cachexia:4 main clinical manifestations of cachexia:• AnorexiaAnorexia• Chronic nauseaChronic nausea• AstheniaAsthenia• Change in body imageChange in body image

Pharmacologic treatment of cachexia is Pharmacologic treatment of cachexia is targeted principally at anorexia and targeted principally at anorexia and chronic nausea chronic nausea (Bruera, 1993)(Bruera, 1993)

Pharmacological ApproachesPharmacological Approaches The main pharmacologic approaches include:The main pharmacologic approaches include:

• CorticosteroidsCorticosteroids• Progestational agents (ie, megestrol acetate)Progestational agents (ie, megestrol acetate)• Cannabinoids (ie, dronabinol)Cannabinoids (ie, dronabinol)• Antihistamines (ie, cyproheptadine)Antihistamines (ie, cyproheptadine)• Unique agents (ie, hydrazine sulfate)Unique agents (ie, hydrazine sulfate)• Omega-3 fatty acids,Omega-3 fatty acids, EPA and docosahexaneoic acid EPA and docosahexaneoic acid

(DHA) (n-3s) (DHA) (n-3s) (Barber, et al, 2000; Hussey & Tisdale, 1999; Wigmore, (Barber, et al, 2000; Hussey & Tisdale, 1999; Wigmore, et al, 2000)et al, 2000)

Results of trials for cachexia have been mixed Results of trials for cachexia have been mixed (Bruera, et al, 1985;(Bruera, et al, 1985; Gold, 1975; Lener & Regelson, 1976; Silverstein, et al, Gold, 1975; Lener & Regelson, 1976; Silverstein, et al, 1989; Tayek, et al, 1987; Wadleigh, et al, 1990)1989; Tayek, et al, 1987; Wadleigh, et al, 1990)

Ongoing and Future WorkOngoing and Future Work

Anabolic steroidsAnabolic steroids Protein shakesProtein shakes Weight lifting with creatineWeight lifting with creatine OlanzapineOlanzapine

Fatigue and ChemobrainFatigue and Chemobrain

FatigueFatigue

Highly prevalent – effecting 2/3s of Highly prevalent – effecting 2/3s of patientspatients

Very disablingVery disabling Also makes the job of caregiving Also makes the job of caregiving

more stressful and exhausting for more stressful and exhausting for familyfamily

Fatigue – what works?Fatigue – what works?

ExerciseExercise Modifications in dietModifications in diet Stimulant medicationsStimulant medications

ChemobrainChemobrain

What really is chemobrain?What really is chemobrain?• Subjective sense of slowed thinking, Subjective sense of slowed thinking,

muddy thinking, lack of flexibility in muddy thinking, lack of flexibility in cognitive processescognitive processes

• Poor concentration and secondarily, Poor concentration and secondarily, poor memorypoor memory

What causes it?What causes it?• Chemo? Hormones? Other meds? Chemo? Hormones? Other meds?

Chemobrain – What works?Chemobrain – What works?

StimulantsStimulants Meditation?Meditation? Anti-depressants?Anti-depressants? Medications that increase red blood Medications that increase red blood

cell counts (ie epo)?cell counts (ie epo)?

Insomnia and Hot Insomnia and Hot FlashesFlashes

InsomniaInsomnia

Highly prevalent symptomHighly prevalent symptom• 53% of people with cancer report 53% of people with cancer report

difficulty sleepingdifficulty sleeping• Breast cancer Breast cancer

Multiple problems can lead to poor sleepMultiple problems can lead to poor sleep• PainPain• Hot flashesHot flashes• Worry Worry

InsomniaInsomnia

Multiple new sleep aids on the Multiple new sleep aids on the marketmarket• Eszopiclone Eszopiclone • RemelteonRemelteon

None evaluated in people with cancerNone evaluated in people with cancer

An oldie but a goodieAn oldie but a goodie• Trazadone (only hot flas med that is Trazadone (only hot flas med that is

sedating and can be taken at bedtime)sedating and can be taken at bedtime)

Hot FlashesHot Flashes

Highly prevalentHighly prevalent Vary tremendously in frequency and Vary tremendously in frequency and

intensity from patient to patientintensity from patient to patient Can be part of a viscious circleCan be part of a viscious circle

Hot FlashesHot Flashes

Antidepressants work bestAntidepressants work best• SNRIs (venlafaxine and possibly duloxetine) SNRIs (venlafaxine and possibly duloxetine) • SSRIsSSRIs• Others?Others?• Olanzapine (?) Olanzapine (?)

Most of the herbal and supplement based Most of the herbal and supplement based treatments in effectivetreatments in effective• Loprinzi latest was negative trial of black Loprinzi latest was negative trial of black

cohoshcohosh

www.cancer.govwww.cancer.gov

Follow links to PDQFollow links to PDQ

Supportive CareSupportive Care

ConclusionsConclusions

People with cancer are living longerPeople with cancer are living longer The focus is on quality of life in addition to The focus is on quality of life in addition to

quantityquantity People surviving cancer want to live People surviving cancer want to live

normal livesnormal lives People with cancer have multiple People with cancer have multiple

symptomssymptoms New treatments of various kinds are New treatments of various kinds are

available and there is no need to sufferavailable and there is no need to suffer