How to Mitigate the Long-Term Effects of Treatment

1. 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

2. 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

3. 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

4. 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

5. 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

6. Women with MBCa Have Many Choices • Medical interventions • Psychological interventions • Alternative therapies • Exercise and physical therapeutic interventions

7. Pain

8. 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

9. Communicating About Pain • Communicate • Intensity • Location • What the pain feels like • What makes it worse • What helps

10. 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

11. Future Developments in Pain • Rapid onset opioids • Oxymorphone • “Smart” pills • Alvimopan

12. Depression

13. 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

14. Diagnosing Depression in Cancer Patients • Reliable Symptoms • Anhedonia • Persistent depressed mood • Unreliable Symptoms • Fatigue, insomnia, decreased libido, eating disturbances, situational emotional reactions

15. Patient-MD Concordance for Depression Ratings

16. Patient-Nurse Concordance For Depression Ratings

17. 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

18. Alternative Treatments for Depression • Fish oil • Exercise • Yoga, meditation

19. Nausea and Vomiting

20. 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)

21. 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)

22. Alternative Treatments • Relaxation • The sacrificial lamb approach • Wrist bands • Acupuncture

23. Maintaining Weight and Muscle Mass

24. 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)

25. 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)

26. 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)

27. Ongoing and Future Work • Anabolic steroids • Protein shakes • Weight lifting with creatine • Olanzapine

28. Fatigue and Chemobrain

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

30. Fatigue – what works? • Exercise • Modifications in diet • Stimulant medications

31. 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?

32. Chemobrain – What works? • Stimulants • Meditation? • Anti-depressants? • Medications that increase red blood cell counts (ie epo)?

33. Insomnia and Hot Flashes

34. 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

35. 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)

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

37. 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

38. www.cancer.gov Follow links to PDQ Supportive Care

39. 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