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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 3 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 2 4 1 3/10/2016 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 5 (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)) 7 – 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 6 (American Society of Clinical Oncology. About Cancer Survivorship. http://www.cancer.net/survivorship/about-survivorship) 8 2 3/10/2016 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/.) 11 9 10 (National Comprehensive Cancer Network. Survivorship (Version 2.2015)) 12 3 3/10/2016 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 13 15 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 14 (National Comprehensive Cancer Network. Survivorship (Version 2.2015)) 16 4 3/10/2016 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/) 17 19 (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 18 20 (National Comprehensive Cancer Network. Survivorship (Version 2.2015); Anderson BL, DeRubeis RJ, Berman BS, et al.. J Clin Oncol 32(18): 1605-1619) 5 3/10/2016 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) 21 23 (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) 22 (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 24 (National Comprehensive Cancer Network. Survivorship (Version 2.2015); Anderson BL, DeRubeis RJ, Berman BS, et al.. J Clin Oncol 32(18): 1605-1619) 6 3/10/2016 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) 25 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)) 27 (National Comprehensive Cancer Network. Survivorship (Version 2.2015)) 26 (National Comprehensive Cancer Network. Survivorship (Version 2.2015)) 28 7 3/10/2016 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) 29 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)) 31 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 30 (National Comprehensive Cancer Network. Survivorship (Version 2.2015)) 32 8 3/10/2016 Fatigue Management Patient/ Family Education Physical Activity Psychosocial; Nutrition; Sleep Hygiene Cancer Survivorship Guidelines Pharmacologic (National Comprehensive Cancer Network. Survivorship (Version 2.2015)) 33 Pharmacologic Agents for the Management of Fatigue Available at www.NCCN.org 35 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. ) 34 Available at http://www.instituteforquality.org/practice-guidelines 36 9 3/10/2016 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) 37 Treatment Summary and Survivorship Care Plan Available at http://www.asco.org/practice-research/cancer-survivorship 39 Chemotherapy Passport at Memorial Cancer Institute 38 40 10 3/10/2016 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)) 41 Survivorship Resources, continued 43 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)) 42 44 11 3/10/2016 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 45 47 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 46 48 12 3/10/2016 Questions 49 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. 50 13