Russell Goldman MD, MPH, CCFP Ramona Mahtani MD, CCFP

1. A Transformative Year for Palliative CareTop Practice Changing (or Practice Validating) Articles2013-2014 Russell Goldman MD, MPH, CCFP Ramona Mahtani MD, CCFP

2. Disclosure: past 2 years April 2014: “pain management in the elderly” for oncologists sponsored by Purdue December 2013: Advisory Board participant for Teva Pharmaceuticals on SL fentanyl

7. Transformative Paradigm in Palliative Care

9. What’s Already Known… Many patients with metastatic cancer receive chemotherapy in their final months WITHOUT information on survival, future care, quality of life and location of death Patients who receive chemo within 2 weeks of death are less likely to receive hospice services, compared with those who do not

10. Objective of Study: Is there an association with chemotherapy in patients last MONTHS of life and intensive medical care in the ICU in their last WEEK? -More likely to die in ICU? -More likely to receive CPR, mechanical ventilation, both? -Late referrals to hospice(home palliative care/PCU)? -Less likely to die in preferred place?

12. Methods • Participants baseline Interview • Medical Chart Review at study enrollment: • Confirmation with Physician: performance status and prognosis <6mo

13. Additional Covariates Measured at Baseline • Sociodemographic characteristics • Health Status Measures: • McGill Quality of Life Index, Charlson Comorbid Index, ECOG, Karnofskyscore • Treatment preferences

14. Sample Patient Interview “If you could choose, would you prefer: 1) a course of treatment that focused on extending life as much as possible, even if it meant more pain and discomfort, or 2) on a plan of care that focused on relieving pain and discomfort as much as possible, even if that meant not living as long?” “Would you take chemotherapy and risk side effects such as…or have to spend more time in the hospital if it would keep you alive for ‘___’ time…”

15. Q for Patient: “Do you think it would be a bad thing for a person to die in the ICU versus elsewhere (e.g., home, hospital, and hospice)?” Q for Caregiver: “Do you think that (PLACE OF DEATH) was where (PATIENT) would have most wanted to die?”

16. Results 56% participants were receiving palliative chemo on study enrollment (N=386) Died median of 4 months (1.8-8.3 m0) after enrollment in study Survival same in both groups

18. Total Yes Chemo No Chemo

22. What do you think?

23. Author’s conclusions Our study has important implications for oncology providers, patients with advanced cancer, and caregivers facing decisions about treatment. It suggests that end of life discussions may be particularly important for patients receiving palliative chemotherapy, who should be informed by data on the likely outcomes associated with its use. The findings also suggest the need for oncology providers to elicit patients’ preferred site of death to ensure that patients’ end of life experiences are congruent with their values.

24. “Palliative Chemotherapy” as an exclusion criteria for Palliative Care Programs? “Time-outs” involving interdisciplinary & interprofessional teams to reflect & avoid inadvertently ‘treating ourselves’ in offering interventions without benefit & with potential to harm at end of life

25. Advance Care Planning discussions need to consider the longer-term path patient’s and family’s are sent on when decisions are made earlier in their disease trajectory

26. Emerging, Practical Evidence Base

27. Purpose Cancer patients at end of life majority in hospital receive parenteral hydration; majority in “hospice” do not Limited evidence supporting either practice RCT to determine the effect of hydration on symptoms associated with dehydration, quality of life, and survival in patients with advanced cancer

29. Methods • Intervention • 1000 ml SC daily over 4 hours • Control • 100 ml SC daily over 4 hours • Blinding: different nurse started infusion; pump in a backpack with counterweight • End point • Unresponsive; progressive coma or died

30. Measures “fatigue, myoclonus, sedation, hallucinations, pain, nausea, depression, anxiety, drowsiness, shortness of breath, appetite, feelings of well-being, and sleep, was assessed using the Edmonton Symptom Assessment Scale (ESAS)” Primary outcome change in sum of four dehydration symptoms (bold) day 4 and baseline

31. Measures (cont) Memorial Delirium Assessment Scale Richmond Agitation Sedition Scale (RASS) Nursing Delirium Screening Scale (NuDESC) Unified Myoclonus Rating Scale (UMRS) QoL and fatigue during the last 7 days using the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) questionnaire. Physical assessement (mucous membranes, axillary moisture & sunkenness of eyes Baseline, day 4 and then q3-5 days

32. Results

33. Results • No significant differences between the two groups for: • Change in the sum of four dehydration symptoms (−3.3 v −2.8, P = .77), ESAS (all nonsignificant) • MDAS (1 v 3.5, P = .084), • NuDESC (0 v 0, P = .13), • UMRS (0 v 0, P = .54) by day 4. • Results for day 7, including FACIT-F, were similar • Survival did not differ between the two groups (median, 21 v 15 days, P = .83).

34. What do you think?

35. Author’s Conclusions “In conclusion, our results suggest that in patients with advanced cancer who are mildly to moderately dehydrated and within days to weeks of death, parenteral hydration at 1,000 mL per day does not improve symptoms associated with dehydration, QoL, or survival as compared with placebo”.

36. Author’s Conclusions (cont) “Our study supports current hospice practice of not administering hydration routinely. Further studies are required to determine whether any subgroups, such as delirious patients or those with longer survival, would benefit from parenteral hydration”

38. What’s already known Cochrane Review (2010) – mixed results for all pharmacologic treatment vs. placebo for CRF Prior positive studies did not use validated outcome measures, not adequately powered No Double-Blind, Randomized Placebo Controlled Trial

39. Primary Objective: Effect of Dexamethasone and Placebo on CRF using validated instrument Secondary Objective: Role of Dexamethasone in anorexia, anxiety, depression and symptom distress scores Location: Outpatient clinic for pain management, palliative care, Oncology at 4 unique sites

40. Inclusion Criteria • Advanced cancer • Moderate to Severe CRF clinical cluster symptoms = ≥ 3 symptoms during previous 24hrs (pain, fatigue, nausea, anorexia/cachexia, sleep problems, depression, poor appetite) with ≥ 4 on ESAS • Normal cognition • No infection • Hemoglobin >90 within week of enrollment • Life expectancy ≥4 weeks • No AIDS • ANC ≥750 within week of enrollment • No diabetes in last 2 weeks and no surgery in last 2 weeks

41. Intervention Dexamethasone 4mg OR Placebo po bid x 14d

42. Outcome Measures • FACIT-F: • validated, quality of life instrument (CRF clinical trials) • 27 general quality of life questions divided into 4 domains (physical, social, emotional, functional) • 13 item FACIT-F fatigue subscale • FAACT • ESAS • HADS • Monitored for Adverse Events (National Cancer Institute Common Toxicity Criteria)

44. ‘No interest’ + ‘Too much burden’=25%

46. Mean Difference =5.9

47. Mean difference= -6.0

49. What do you think?

50. Limitations! Dose Duration Beyond 2 weeks -- Effects wane, Adverse effects increase Cluster Symptoms Not assessing an integrated holistic, multidisciplinary approach