1. Exercise & Cancer Rehabilitation Lee W. Jones, Ph.D. Behavioral Medicine Laboratory, Faculty of Physical Education, University of Alberta Behavioral Medicine Laboratory, Faculty of Physical Education, University of Alberta HE ED 221 (E-121) November 24, 1.00-2.00pm, 2003 HE ED 221 (E-121) November 24, 1.00-2.00pm, 2003

2. Framework PEACE PreventionPrevention1.Pre-Treatment1.Pre-Treatment DIAGNOSISDIAGNOSIS 2.Treatment2.Treatment 4.Palliation4.Palliation 3.Rehabilitation3.Rehabilitation 5.Survival5.Survival Adapted from Courneya & Friedenreich, Ann Behav Med 2001 PRE-DIAGNOSISPRE-DIAGNOSISPOST-DIAGNOSISPOST-DIAGNOSIS

3. Why Exercise?

4. Cancer Therapies Surgery Tx for localized tumors 60% pts, 30% cure rate Surgery Tx for localized tumors 60% pts, 30% cure rate Radiation Local – regional tx 50% patients Radiation Local – regional tx 50% patients Systemic Therapy Advanced solid tumors Chemotherapy;hormonal therapy; biological therapy Systemic Therapy Advanced solid tumors Chemotherapy;hormonal therapy; biological therapy

5. Cancer & Quality of Life - Psychological/physical & functional side-effects Surgery - infection, loss of function, dyspnea, pain, diarrhea, lymphedema Surgery Radiation - nausea, fatigue, vascular damage (cardiac & lung tissue) Radiation Chemotherapy - myelosuppression, nausea, weight gain, cardiac toxicity, fatigue Chemotherapy Shapiro NEJM 2001 344:1997-2008

6. Current Quality of Life Interventions - Cognitive-behavioral therapies, educational strategies, grp psychotherapy - Largely psychological in nature - Unlikely to address physical/functional aspects - Exercise – not important or appropriate - Cognitive-behavioral therapies, educational strategies, grp psychotherapy - Largely psychological in nature - Unlikely to address physical/functional aspects - Exercise – not important or appropriate Courneya, Mackey & Jones Phys SportsMed 2000

7. Cancer, Quality of Life, & Exercise Clinical Concerns: -Immunosuppressive effects -Pathological bone fractures -  Cardiotoxicity (RT & CT) - Unwillingness of cancer pts - Recent research – dispelling myths Clinical Concerns: -Immunosuppressive effects -Pathological bone fractures -  Cardiotoxicity (RT & CT) - Unwillingness of cancer pts - Recent research – dispelling myths Courneya, Mackey & Jones Phys SportsMed 2000

8. Current Status – Exercise & Cancer Research

9. Review of Literature Cancer Site Study Design Adjuvant Tx Exercise Modality

10. Review of Literature Courneya et al. Phys SportsMed 2000;28:49; Courneya ACSM; 2003 All reported significant benefits No Adverse events Multiple Outcomes….. All reported significant benefits No Adverse events Multiple Outcomes….. Outcomes/ResultsOutcomes/Results Physiologic Outcomes - VO 2peak, body comp, NK activity, flexibility Tx-Related Symptoms – fatigue, pain, nausea, diarrhea, platelet transfusion, hospital stay QOL Outcomes – overall, PWB, FWB, SWB, SWL, anx/dep

11. Review of Literature Small number of studies (n=47; only 14 RCT’s) Small sample sizes (heterogeneous) Self-report measures of exercise Methodology not well described Small number of studies (n=47; only 14 RCT’s) Small sample sizes (heterogeneous) Self-report measures of exercise Methodology not well described LimitationsLimitations Courneya et al. Phys SportsMed 2000;28:49; Courneya ACSM; 2003

12. V. Clinical Exercise Prescription Guidelines

13. Cancer dx affects all aspects of physical functioning Unique manifestations - Tumor - Tumor - Treatment - Treatment - Side effects - Side effects - Demographic profile - Demographic profile ACSM guidelines (3-5d/wk, 30-60mins, moderate intensity) Optimal guidelines – not yet established Cancer dx affects all aspects of physical functioning Unique manifestations - Tumor - Tumor - Treatment - Treatment - Side effects - Side effects - Demographic profile - Demographic profile ACSM guidelines (3-5d/wk, 30-60mins, moderate intensity) Optimal guidelines – not yet established General Guidelines

14. Prescription Guidelines Mode Walking / cycle ergometry natural choice Account for specific impairments (e.g., colorectal, breast cancer) Resistance/upper body – lymphedema concerns - unfounded Combined program optimal Walking / cycle ergometry natural choice Account for specific impairments (e.g., colorectal, breast cancer) Resistance/upper body – lymphedema concerns - unfounded Combined program optimal

15. Prescription Guidelines Frequency & Intensity At least 3-5d/wk Daily for deconditioned patients Moderate Intensity 50-70% VO 2max 60-80% HR max RPE 11-14 At least 3-5d/wk Daily for deconditioned patients Moderate Intensity 50-70% VO 2max 60-80% HR max RPE 11-14

16. Prescription Guidelines Duration & Progression 20-30mins (continuous) Intermittment bouts (5-10 mins) Initially in frequency & duration - then intensity Progression slower for deconditioned pts & those suffering severe side effects 20-30mins (continuous) Intermittment bouts (5-10 mins) Initially in frequency & duration - then intensity Progression slower for deconditioned pts & those suffering severe side effects

17. General Guidelines No evidence that one type of exercise is superior Safety is the primary concern Optimal program may combine resistance & aerobic training Key point is to be flexible - modify prescription based on response to treatment(s) No evidence that one type of exercise is superior Safety is the primary concern Optimal program may combine resistance & aerobic training Key point is to be flexible - modify prescription based on response to treatment(s)

18. ComplicationPrecaution ComplicationPrecaution Hemoglobin <8.0 g/dlAvoid high intensity exercise Hemoglobin <8.0 g/dlAvoid high intensity exercise Absolute neutrophil countAvoid exercises that may increase chance of infection (swimming) Absolute neutrophil countAvoid exercises that may increase chance of infection (swimming) Fever > 38 o CAvoid exercise Fever > 38 o CAvoid exercise Ataxia/dizzinessAvoid exercises that require significant balance & coordination (treadmill) Ataxia/dizzinessAvoid exercises that require significant balance & coordination (treadmill) Severe cachexiaLoss of muscle mass limits exercise intensity - modify program accordingly Severe cachexiaLoss of muscle mass limits exercise intensity - modify program accordingly Bone painAvoid high impact exercises Bone painAvoid high impact exercises Extreme fatigueExercise at lower power output, avoid maximal tests Extreme fatigueExercise at lower power output, avoid maximal tests ComplicationPrecaution ComplicationPrecaution Hemoglobin <8.0 g/dlAvoid high intensity exercise Hemoglobin <8.0 g/dlAvoid high intensity exercise Absolute neutrophil countAvoid exercises that may increase chance of infection (swimming) Absolute neutrophil countAvoid exercises that may increase chance of infection (swimming) Fever > 38 o CAvoid exercise Fever > 38 o CAvoid exercise Ataxia/dizzinessAvoid exercises that require significant balance & coordination (treadmill) Ataxia/dizzinessAvoid exercises that require significant balance & coordination (treadmill) Severe cachexiaLoss of muscle mass limits exercise intensity - modify program accordingly Severe cachexiaLoss of muscle mass limits exercise intensity - modify program accordingly Bone painAvoid high impact exercises Bone painAvoid high impact exercises Extreme fatigueExercise at lower power output, avoid maximal tests Extreme fatigueExercise at lower power output, avoid maximal tests Special Precautions

19. VI. Current Clinical Trials & Forthcoming Studies

20. Breast Cancer

21. REHAB Trial REHAB (Rehabilitation Exercise for Health After Breast Cancer) Trial Purpose Determine the effects of exercise training on cardiopulmonary, QOL, and biologic outcomes in postmenopausal b/c survivors Purpose Outcomes QOL, VO 2peak, metabolic hormones (insulin, IGF-1), sex steroid hormones (estradiol, estrogen), biomarkers of CVD (CRP, lipids, etc.) Outcomes

22. REHAB Trial Method 53 participants EG (n=25) or CG (n=28) Cycle ergometry 3x/wk, 15- 35mins, 15wks, 70-75% VO 2peak Results 52 participants completed trial 98.4% adherence (44.3/45 sessions) 53 participants EG (n=25) or CG (n=28) Cycle ergometry 3x/wk, 15- 35mins, 15wks, 70-75% VO 2peak Results 52 participants completed trial 98.4% adherence (44.3/45 sessions)

23. Results VO 2peak QOLQOL Courneya et al. JCO 2003

24. Breast Cancer START (Supervised Trial of Aerobic vs Resistance Training) Objectives 1.Compare AET Vs RET on fitness & QOL 2.Explore individual characteristics of these effects 3.Compare adherence rates 4.Investigate psychosocial determinants Objectives 1.Compare AET Vs RET on fitness & QOL 2.Explore individual characteristics of these effects 3.Compare adherence rates 4.Investigate psychosocial determinants Courneya, et al. Funded by CBCRA Purpose Determine the effects of aerobic vs. resistance training on QOL in early stage b/c patients on chemotherapy Purpose

25. START Trial Study Design 210 Early Stage B/C Patients VancouverN=70OttawaN=70 ProcedureProcedure EdmontonN=70 Tax/Non-TaxTax/Non-Tax Tax/Non-Tax LMRTAELMRTAELMRTAE Eligible Pts Approached by OncologistBaseline Assessment > 1 st CT Intervention Concurrent with CT Post-Test 3wk > Last CT Courneya, et al. Funded by CBCRA

26. START Trial Outcomes Primary: QOL Secondary: Fatigue; VO 2peak ; Muscular Strength; Body Composition; Lymphedema; Bio-markers (Cancer Recurrence & CV Risk Factors) Outcomes Primary: QOL Secondary: Fatigue; VO 2peak ; Muscular Strength; Body Composition; Lymphedema; Bio-markers (Cancer Recurrence & CV Risk Factors) Progress Edmonton (n=21; 83%) Ottawa (n=18) Vancouver (n=3) Progress Edmonton (n=21; 83%) Ottawa (n=18) Vancouver (n=3) Courneya, et al. Funded by CBCRA

27. Prostate Cancer

28. Prostate Trial Prostate and Resistance Exercise Training Trial Purpose Determine the effects of resistance exercise on fatigue & HRQOL in prostate cancer patients receiving ADT. Outcomes HRQOL, fatigue, body composition, muscular fitness (strength, cardiopulmonary fitness) Purpose Determine the effects of resistance exercise on fatigue & HRQOL in prostate cancer patients receiving ADT. Outcomes HRQOL, fatigue, body composition, muscular fitness (strength, cardiopulmonary fitness) Segal et al. JCO 2003

29. REHAB Trial Prostate Trial Method 155 RET (n=83) or CG (n=73) Resistance Training 3x/wk, 12wks, 9 exercises, 2 sets of 8- 12 reps @ 60-70% 1 RM Results 135 participants completed 76.2% adherence (27/36 sessions) Method 155 RET (n=83) or CG (n=73) Resistance Training 3x/wk, 12wks, 9 exercises, 2 sets of 8- 12 reps @ 60-70% 1 RM Results 135 participants completed 76.2% adherence (27/36 sessions)

30. Prostate Results Chest Press FatigueFatigue Leg Press QOLQOL

31. Colorectal Cancer

32. CAN-HOPE RCT Colorectal RCT (CAN-HOPE) To determine if exercise can improve QOL in colorectal cancer survivorsTo determine if exercise can improve QOL in colorectal cancer survivors Submaximal fitness test/QOL at baseline & 16 weeksSubmaximal fitness test/QOL at baseline & 16 weeks Moderate intensity, home- based exercise program (F=3-5/wk; D=20-30)Moderate intensity, home- based exercise program (F=3-5/wk; D=20-30) Randomized 102 patients (33 Control /69 EX)Randomized 102 patients (33 Control /69 EX) Colorectal RCT (CAN-HOPE) To determine if exercise can improve QOL in colorectal cancer survivorsTo determine if exercise can improve QOL in colorectal cancer survivors Submaximal fitness test/QOL at baseline & 16 weeksSubmaximal fitness test/QOL at baseline & 16 weeks Moderate intensity, home- based exercise program (F=3-5/wk; D=20-30)Moderate intensity, home- based exercise program (F=3-5/wk; D=20-30) Randomized 102 patients (33 Control /69 EX)Randomized 102 patients (33 Control /69 EX) Courneya et al. EJCC, in press

33. CAN-HOPE RCT Participant Characteristics Demographic Age: 60; 59% male 74% married; 40% university 60% >$40k Participant Characteristics Demographic Age: 60; 59% male 74% married; 40% university 60% >$40k Medical Mths Sx: 2 80% III/IV; 100% Sx; 20% RT; 65% CT Medical Mths Sx: 2 80% III/IV; 100% Sx; 20% RT; 65% CT

34. CAN-HOPE Results TOI QOL Anxiety  Fitness  Fitness Courneya et al. EJCC, in press

35. Lung Cancer

36. Exercise Capacity & NSCLC Purpose Determine the Prognostic Value of Symptom-Limited Exercise Testing on Survival in Inoperable NSCLC Patients Purpose Method New Patient Rounds via Medical Record Review Blood draw/PFT/GXT Method New Patient Rounds via Medical Record Review Blood draw/PFT/GXT Jones et al. In Process

37. Exercise Capacity & NSCLC Outcomes Primary: Survival Secondary: -Association with traditional predictors -VO 2peak & Tx response/tolerability Outcomes Primary: Survival Secondary: -Association with traditional predictors -VO 2peak & Tx response/tolerability Jones et al. In Process

38. Exercise Capacity & NSCLC ProgressProgress Total Number of Patients Screened N=49 Total Number of Patients Eligible N=20 (20/49 = 41%) Total Number of Patients Interested N=12 (12/20 = 65%) Total Number of Patients Tested N=10 (10/12 = 83%) Reasons for Non-Eligibility (n=29) Recent CHD (n=4) Physically Disabled (n=7) TB (n=1) Age (n=2) O2 Dependent (n=5) Extensive Met Disease (n=4) Psychological Distress (n=2) Co-morbidities (n=4) Non Lung Cancer (n=1) No Treatment (n=1) Reasons for Non-recruitment (n=8) Does Not Believe in Exercise (n=1) Exercise Test Too Risky (n=1) Too Sick (n=3) Too Much On (n=3) Jones et al. In Process

39. Exercise Capacity & NSCLC Results Age: 71 Range: 64 - 83 VO 2peak : 16.2Range: 9.4 – 24.3RER: 1.2 BMI: 27Range: 21 – 35 Results Age: 71 Range: 64 - 83 VO 2peak : 16.2Range: 9.4 – 24.3RER: 1.2 BMI: 27Range: 21 – 35 Aims: Accurate prognostic information ‘Optimal’ therapeutic approach Feasibility & safety - RCT Aims: Accurate prognostic information ‘Optimal’ therapeutic approach Feasibility & safety - RCT

40. Pre Surgery Exercise RCT Jones et al. In Progress Outcomes Primary: Perioperative Complications (infection, O 2 utilization, etc.) Secondary: VO 2peak, QOL, length of hospital stay Outcomes Primary: Perioperative Complications (infection, O 2 utilization, etc.) Secondary: VO 2peak, QOL, length of hospital stay Method Surgeon Referral Two-armed RCT – Exercise Training (n=25) vs. Usual Care (n=25) AET 4/5x/wk, 10-45mins, 50-75% VO 2peak for 6 wks Method Surgeon Referral Two-armed RCT – Exercise Training (n=25) vs. Usual Care (n=25) AET 4/5x/wk, 10-45mins, 50-75% VO 2peak for 6 wks Timing of Assessments: baseline, pre-sx, 5-7d post sx

41. Other Cancers

42. Exercise & Anemia Trial Mackey, Courneya, Jones et al. Funded by Amgen Inc EXTRA (EXercise TRaining & Anemia) Trial Outcomes Primary: QOL (FACT-An) Secondary: VO 2peak, Hb Response, Blood Markers Outcomes Primary: QOL (FACT-An) Secondary: VO 2peak, Hb Response, Blood Markers Purpose Determine if a 12-wk exercise program can improve QOL in anemic patients receiving Aranesp Purpose Method Two-armed RCT – Aranesp Alone (n=50) vs. Aranesp + Exercise (n=50) Periodized Cycle Ergometry 3x/wk, 30-45mins, 60-75% VO 2peak for 12 wks Method Two-armed RCT – Aranesp Alone (n=50) vs. Aranesp + Exercise (n=50) Periodized Cycle Ergometry 3x/wk, 30-45mins, 60-75% VO 2peak for 12 wks

43. EXTRA Trial Results Age: 51 Range: 25 - 71 VO 2peak : 16.5Range: 11 – 25.3RER: 1.23 Hb: 100Range: 91 - 107 Results Age: 51 Range: 25 - 71 VO 2peak : 16.5Range: 11 – 25.3RER: 1.23 Hb: 100Range: 91 - 107

44. Purpose Examine the Potential Role of Exercise in Multiple Myeloma Cancer Patients Purpose Objectives 1.Exercise preferences/level of interest 2.Exercise Rates 3.Determinants of exercise (attitudes, perceived capability) 4.Association with QOL & fatigue Objectives 1.Exercise preferences/level of interest 2.Exercise Rates 3.Determinants of exercise (attitudes, perceived capability) 4.Association with QOL & fatigue Multiple Myeloma Jones et al. In Process

45. Exercise & Multiple Myeloma Method Cross-sectional provincial survey – ACB registry Oncologist-approval 162 sent questionnaire Method Cross-sectional provincial survey – ACB registry Oncologist-approval 162 sent questionnaire Results 11 returned (6 deceased, 5 moved) 87 (87/151 = 58%) completed questionnaire Results 11 returned (6 deceased, 5 moved) 87 (87/151 = 58%) completed questionnaire Jones et al. In Process

46. Exercise & Glioma RCT Purpose To determine the effect of exercise training on QOL in newly diagnosed primary glioma cancer patients during RT Purpose Jones et al. Submitted for Funding CIHR/ACB Method Two-armed RCT: usual care (n=12) vs. exercise training (n=12) Method Intervention 3x/wk; 60-90 minutes, 8wks AET: 50-70% VO 2peak RET: 8-12 repetitions @ 70-80% 1-RM of 8 upper/lower body exercises Intervention 3x/wk; 60-90 minutes, 8wks AET: 50-70% VO 2peak RET: 8-12 repetitions @ 70-80% 1-RM of 8 upper/lower body exercises

47. Summary ACSM Guidelines – Early Stage Patients Integral component of comprehensive care for cancer patients Advanced Cancer Pts – More Care Safety primary concern