Cancer Across the Lifespan: Focus on Supportive Care

Transcription

1 Cancer Across the Lifespan: Focus on Supportive Care Traci M. White, PharmD, PhC Assistant Professor UNM College of Pharmacy Pharmacist Clinician Mesilla Valley Hospice

2 Objectives Identify common symptoms related to end stage cancer, including etiology Describe the role of palliative care in oncology Recommend appropriate palliative pharmacologic management of common symptoms Describe appropriate assessment of response to palliative pharmacologic intervention

3 Cancer as a Chronic Condition A changing landscape More treatment options Better screening modalities Improved symptom control with newer targeted treatments Increased experimental options Low grade lymphomas, chronic leukemias, multiple myeloma, hormone sensitive cancers Witter D. OncoLog 2008;53(4)

4 Key advances in the history of cancer chemotherapy. DeVita V T, and Chu E Cancer Res 2008;68: by American Association for Cancer Research

5 Key advances in the history of cancer chemotherapy. DeVita V T, and Chu E Cancer Res 2008;68: by American Association for Cancer Research

6 Imatinib in chronic myelogenous leukemia (CML)

7 Oncologic Drugs Approved in 2015 Drug Cancer Type Target Alectinib (Alecensa) Metastatic NSCLC ALK positive tumors Cobimetinib (Cotellic) Melanoma BRAF V600E or V600K Daratumumab (Darzalex) Multiple myeloma CD38 Elotuzumab (Empliciti) Multiple myeloma SLAMF7 Panobinostat (Farydak) Multiple myeloma HDAC inhibitor Palbociclib (Ibrance) Breast ER+, HER-2 - Talimogene laherparepvec (Imlygic) Unresectable recurrent melanoma HSV 1 oncolytic virus Levatinib (Lenvima) Thyroid Multitargeted TKI Trifluridine/Tipiracil (Lonsurf) Metastatic colon Antimetabolite Ixazomib (Ninlaro) Multiple myeloma Proteosome inhibitor Sonidegib (Odomzo) Locally advanced basal cell Hedgehog pathway inhibitor

8 Oncologic Drugs Approved in 2015 Irinotecan liposomal (Onivyde) Drug Cancer Type Target Metastatic pancreatic Topoisomerase 1 inhibitor Nivolumab (Opdivo) Metastatic NSCLC PD-1 inhibitor Necitumumab (Portrazza) Metastatic NSCLC EGFR inhibitor Osimertinib (Tagrisso) NSCLC EGFR T790M mutation Dinutuximab (Unituxin) Rolapitant (Varubi) Trabectedin (Yondelis) High-risk neuroblastoma (pediatrics) Prevention of delayed chemo-induced n/v Liposarcoma or leiomyosarcoma GD-2 NK-1 antagonist G2/M phase cycle specific

9 Annual Report to the Nation on the Status of Cancer Collaboration of the ACS, CDC, NCI and the North American Association of Central Cancer Registries Overall decreased incidence of 0.7% per year Death rates continued to decline by average of 1.5% per year Ryerson AB, et al. Cancer 2016 (Mar 9)

10 Incidence Rates

11 10 Year Mortality Trends

12 Pediatric Malignancies Curative therapies developed over the last 50 years have made longterm survival into adulthood the expectation for >80% of children with access to these therapies Surgeries, chemotherapy, radiation therapy, stem cell transplant Late effects contribute to a high burden of morbidity in survivors 60-90% develop 1 or more chronic health conditions 20-80% experience severe or life-threatening complications during adulthood

13 Factors that Affect the Risk of Late Effects Tumor-related Type, location, how tissues and organs are affected Treatment-related Use of 2 or more modalities Blood product transfusions Chronic graft vs. host disease Patient-related Age and developmental stage at time of diagnosis Length of time since treatment Changes in hormone status and genes Family history

14 Second Cancers Solid tumors Radiation Breast cancer chest radiation for HL Thyroid cancer Brain tumors Bone and soft tissue tumors Lung cancer Chemotherapy MDS or AML Essig, et al. Lancet Oncol 2014 Jul;15(8):841-51

15 Survivorship Physical symptoms/conditions Lymphedema Cardiomyopathy, CHF Neuropathy Osteoporosis Chronic fatigue Psychological effects Anxiety Fear Depression Source: Data Modeling Branch,, Division of Cancer Control and Population Sciences, National Cancer Institute DeSantis CE, et al. CA Cancer J Clin 2014;64:

16 Development of Chemotherapy Regimen

17 Supportive Care During Treatment Focus on improving quality of life through symptom management: Anemia Constipation/diarrhea Cachexia Fatigue Dermatologic toxicity Mucositis Nausea/vomiting Long-term complications

18 WHO Definition of Palliative Care An approach that improves the quality of life of patients and their families facing the problem associated with life-threatening illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial and spiritual

19 What is Palliative Care? Specialized medical care for people with serious illness Focused on providing patients with relief from the symptoms, pain and stress of a serious illness whatever the diagnosis Improves quality of life for both the patient and the family Palliative care is ALWAYS a part of hospice, but hospice is NOT always a part of palliative care

20 Palliative Care and the Triple Aim

21 Delivery of Palliative Care Basic palliative skills Specialty palliative care Facilitate communication von Gunten C, et al. JAMA 2002;287(7):

22 Palliative Care and Oncology Temel et al NEJM 2010;363: Phase III randomized, controlled, single institution, non-blinded clinical trial comparing palliative care plus standard oncology care, begun at the time of diagnosis, to standard oncology care 151 patients with newly-diagnosed metastatic non-small cell lung cancer Intervention: a baseline evaluation and follow-up, at least once per month, by members of a multidisciplinary PC team comprised of 7 palliative care clinicians Primary Outcome: QOL Secondary outcomes: mood, aggressive treatment at EOL

23 Palliative Care and Oncology Results in intervention arm Better understanding of the disease, prognosis, and options Significantly higher QOL scores (p=0.03) Fewer depressive symptoms (p=0.01) Less aggressive end of life care (p=0.05) Less use of chemotherapy near end of life Less hospitalization and intubation More and longer use of hospice Survival 2.7 months longer (p=0.02)

24 Causes of Suffering for Patients with Advanced Cancer Ferris FD, et al. J Clin Oncol 2009;27:

25 Symptom Prevalence in Cancer Systematic review of most common symptoms in end stage cancer in last 7-14 days of life Fatigue 88% Weight loss 86% Weakness 70% Appetite loss 56% Pain 45% Dyspnea 39% Dry mouth 34% Nervousness/anxiety 30% Constipation 29% Depressed mood 19% Teunissen, W et al. JPSM 2007:1:94-104

26 Commonly Used Medications Analgesics (opioids and non-opioids) Benzodiazepines Corticosteroids Anticholinergics Antipsychotics Laxatives Antidepressants

27 Individualized Approach Anticipate symptoms based on disease state(s) Use of standard assessments Frequent evaluation and re-evaluation Utilize a medication that treats multiple symptoms to reduce polypharmacy Discontinue medications that no longer contribute to symptom management Anticipate and treat side effects

28 Pain Management Complete the pain assessment Match the appropriate drug to the pain type Consider potential risks and side effects Assess the safest route of delivery Consider who will administer the meds and in what setting Determine whether the patient can find and afford the medication Assess the cultural, spiritual, and social context for the pain

29 Short-Acting Opioids Medication Onset Peak Effect Duration Common starting doses Morphine Hydromorphone PO: min IV: 1-2 min PO: min IV: min PO: 3-6 hrs IV: 2-4 hrs 5 mg PO q4h PRN 1 mg PO q3-4h PRN Oxycodone PO: min PO: min PO: 3-6 hrs 5 mg PO q4h PRN Hydrocodone 5 mg PO q4h PRN Fentanyl IV: < 1 min IV: < 5 min hrs 25 mcg IV q15min

30 Long-Acting Opioids Oral agents Morphine ER (MS Contin), oxycodone ER (Oxycontin), hydromorphone ER (Exalgo), oxymorphone ER (Opana SR) Onset of action 1-2 hrs Plateau effect 3-8 hrs, duration 8-12 hrs Can dose escalate q24 hrs Transdermal Fentanyl Slow onset of action hrs Duration of action hrs Should only dose escalate q72 hrs Fentanyl stays in circulation for up to 24 hrs after patch removal

31 Methadone Should only be prescribed/adjusted by provider with adequate training and experience Complex PK properties Basic, lipophilic drug onset minutes after oral Oral bioavailability: 70-80% Widely distributed, retained in tissues Extensively metabolized (3A4, 2B6, 2C8, 2C9, 2C19, 2D6; many drug interactions) Elimination half-life: hours (avg hours) Takes 4-10 days to achieve steady-state When initiating therapy and with dosage changes Advantages: Rapid onset of analgesia Effective for neuropathic pain Chemically unrelated to other opioids No active or toxic metabolites Available in many dosage forms Lower incidence of neurotoxic adverse effects Bruera E an d Sweeney C. J Palliat Med2002;5(1):

32 Adjuvant Analgesics Neuropathic pain Tricyclic antidepressants Anticonvulsants Corticosteroids Bone pain NSAIDs Corticosteroids Musculoskeletal spasms Muscle relaxants Benzodiazepines

33 Indices of Therapeutic Effect SUBJECTIVE Pain ratings Description of improved functional status Sleeping better Performing ADLs better Other OBJECTIVE Number of breakthrough doses required Assessment of improved functional status Longer sleep Able to walk further Able to perform activities longer

34 Indices of Adverse Effects SUBJECTIVE Constipation Nausea Sedation Dizziness Confusion Itching Problems with urination OBJECTIVE Bowel movement frequency # of episodes of emesis Vital signs (BP, RR, HR) Pupil size Mini mental status exam

35 Dose Adjustments Educate for good record keeping of PRN doses How many tablets per day do you need to stay comfortable? Make the dosage increases count! Increase the total daily dose of opioid by 25-50% for mild to moderate pain Increase the total daily dose of opioid by % for moderate to severe pain Long-acting, sustained-release opioids can be increased every 24 hours (with the exception of transdermal fentanyl and methadone)

36 Opioid Rotation Lack of therapeutic response Development of adverse effects GI effects Autonomic Cutaneous CNS True opioid allergy Change in patient status

37 Equianalgesic Opioid Dosing EQUIANALGESIC DOSES (MG) DRUG PARENTERAL ORAL Morphine Buprenorphine (SL) Codeine Fentanyl 0.1 N/A Hydrocodone N/A 30 Hydromorphone Meperidine Oxycodone 10* 20 Oxymorphone 1 10 Tramadol 100* 120 McPherson ML. Demystifying Opioid Conversion Calculations: A Guide For Effective Dosing. Amer Soc of Health-Systems Pharm, Bethesda, MD, Copyright ASHP, *Not available in the US

38 Dyspnea Definition: a subjective sensation of difficulty breathing or an abnormally uncomfortable awareness of breathing Causes: Obstructive airway process tracheal obstruction, asthma, COPD Parenchymal/pleural disease aspiration, diffuse primary or metastatic cancer, lymphangitic metastases, pneumonia, pleural effusion, pulmonary drug reaction, radiation pneumonitis Vascular disease - PE, SVC obstruction, pulmonary vascular tumor emboli Cardiac disease CHF, pericardial effusion, arrhythmia, myocardial ischemia Chest wall/respiratory muscles primary neurologic disease, malnutrition Other anxiety, anemia, constipation

39 Dyspnea Assessment Patient rating: Numeric scale (1-10) Physical signs: Sitting up, accessory muscles, nasal flaring ADLs: Impairment of eating, talking, exercise tolerance Lab/X-Ray: Assess the overall goals of care No or minimal diagnostics is reasonable if focus on symptoms

40 Dyspnea Management Non-pharmacologic Re-positioning (avoid lying flat), maintain cool room temps, relaxation exercises, acupuncture, minimal exertion Pharmacologic Oxygen therapy for documented hypoxia esp. COPD Opioids first-line treatment No optimal agent or dose although nebulized route not shown to be superior; consider opioid naïve vs. opioid-tolerant patient Morphine most commonly used Rescue doses at 30-50% of scheduled dose typically effective Anxiolytics Benzodiazepines reserved for breakthrough or refractory dyspnea compounded by anxiety or when ADRs limit titration of opioids to efficacy Jennings AL et al.thorax 2002; 57:939-44

41 Nausea/Vomiting Self-report is gold standard for nausea Associated symptoms, triggers, duration, severity Documentation of vomiting and retching Other monitoring parameters: Food intake Hydration status Bowel movements Documentation of relief from medication

42 Nausea/Vomiting Assessment Smith HS. Ann Palliat Med 2012;1(2):87-93 Sensation of vertigo Vestibular irritation Abdominal pain/ache GERD/ulcer Early satiety or anorexia Compressed stomach Liver metastases Headache with nausea Brain tumor Positional vomiting or vomiting with no nausea Reflux

43 Nausea/Vomiting Management Match the cause of nausea with the most appropriate drug class Stimulation of CTZ (drugs, uremia) dopamine or serotonin antagonist Haloperidol 1-2 mg PO/PR/subQ q4h PRN Movement-related nausea antihistamine Anxiety benzodiazepine Elevated intracranial pressure glucocorticoid (dexamethasone preferred) Constipation laxative GERD proton pump inhibitor

44 Medical Cannabis Dronabinol (Marinol) synthetic THC indicated for chemotherapy related n/v Reserved for 3 rd or 4 th line agent Not very potent Toxicities often unacceptable for elderly patients (i.e. dysphoria) Role of cannabidiol (CBD)? NM Medical Cannabis Program 21 qualifying conditions including cancer, intractable n/v and hospice Not a prescription but a certification

45 Restlessness Falls in the spectrum of delirium Signs may include: Calling out for dead family members or friends Talking about packing bags, taking a trip, going for a care ride Periods of deepening somnolence Agitation Assess for other contributing factors Medication withdrawal, kidney/liver failure, fecal impaction, urinary retention, uncontrolled pain, psychosocial or spiritual problems Treatment Non-pharmacologic interventions Pharmacologic Benzodiazepines Lorazepam 0.5-2mg PO/SL q4h PRN May need to schedule May worsen if delirium Neuroleptic for delirium haloperidol 1-2mg PO/SL q4h PRN

46 Terminal Secretions Known as the death rattle Mean time from onset to death ~16 hrs Type 1 predominately salivary secretions Type 2 predominately bronchial secretions Treatment Discontinue artificial nutrition/hydration Repositioning Oropharyngeal suctioning use only if necessary Anticholinergic meds to dry secretions Atropine, scopolamine, glycopyrrolate, hyoscyamine

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48 Selected Resources Provider education Center to Advance Palliative Care American Academy of Hospice and Palliative Medicine Education in Palliative and End-of-Life Care Palliative Care Fast Facts Patient education