Transcript Exercise in Cancer Patients and Survivors: Benefits and Motivational

Kerry S. Courneya, PhD
Professor and Canada Research Chair
in Physical Activity and Cancer
University of Alberta, Edmonton, Canada
Dr. Courneya indicates that he has no financial
disclosures or conflicts of interest.
Physical Activity and
Cancer Survivorship:
Does the Data Support an
Exercise Prescription?
Kerry S. Courneya, PhD
Professor and Canada Research Chair
in Physical Activity and Cancer
Director, Behavioral Medicine Laboratory
University of Alberta, Edmonton, Canada
(Courneya et al. Res Quart Ex Sport 2015;86:107-116)
PA and Cancer Survival
(Courneya et al. Cancer Therapy 2004;2:1-12)
PA Mechanisms of Improved Survival


reduced risk of cancer recurrence/mortality:

sex hormones (androgens and estrogens).

insulin sensitivity (insulin, IGF-1, IGFBP-3).

immune function (NK cells).

inflammation (IL6, TNFa, leptin, CRP).
reduced risk of other potentially fatal diseases:


lipids, blood pressure, HbA1c.
clinical pathways: body composition, physical fitness, QoL.
PA and Cancer-Specific Mortality
(Schmid & Leitzmann Annals Onc 2014;25:1293-1311)
PA and All-Cause Mortality
(Schmid & Leitzmann Annals Onc 2014;25:1293-1311)
Limitations of PA Research

no randomized trials with survival endpoints.
For observational studies:

none had PA/fitness as primary exposure.

basic assessment of self-reported PA.

no objective measures of PA.

no measures of sedentary behavior.
Limitations of PA Research

few objective fitness assessments (e.g., BMI).

limited biomarker data.

few designed as cancer survivor cohorts.

variable and arbitrary follow-up assessments.

limited disease and treatment data (covariates).

few cancer groups have been examined.
Research on PA & Cancer Outcomes

follow-up of the START Trial (breast).

update of the AMBER Cohort Study (breast).

update of the CHALLENGE (CO.21) Trial (colon).

unpublished prostate cancer survival cohort data.

update of the GAP4 Trial (prostate).

follow-up of the HELP Trial (lymphoma).
Supervised Trial of Aerobic versus
Resistance Training (START)

RCT examining AET versus
RET versus UC in 242 BC
patients on chemotherapy.

multicenter trial: Edmonton,
Ottawa, and Vancouver.
Funded by the Canadian Breast Cancer Research Alliance.
Change in VO2peak (ml/kg/min)
Changes in Aerobic Fitness
UC
RET
AET
1
0.5
0
-0.5
-1
P=.031
-1.5
-2
P=.004
-2.5
(Courneya et al. JCO 2007;25:4396-4404)
Changes in Muscular Strength
UC
RET
AET
Change in strength (kg)
10
8
6
4
P<.001
P<.001
2
0
(Courneya et al JCO 2007;25:4396-4404)
Changes in Lean Body Mass
UC
RET
AET
Change in Lean Mass (kg)
1.4
1.2
1
0.8
0.6
0.4
P=.004
0.2
0
(Courneya et al. JCO 2007;25:4396-4404)
Changes in % Body Fat
UC
RET
AET
Change in % Body Fat
1.2
1
0.8
0.6
0.4
P=.076
0.2
0
(Courneya et al. JCO 2007;25:4396-4404)
Chemotherapy Received (RDI)
Relative Dose Intensity
95
P=.033
90
P=.266
85
80
75
UC
RET
AET
(Courneya et al. JCO 2007;25:4396-4404)
START Trial Outcomes

patients randomized between 2003-2005.

electronic record review in summer 2012.

abstracted events, dates, and treatments.

explored DFS, OS, DDFS, and RFI (STEEP definitions).

Cox proportional hazards models and KM curves.

combined exercise groups and explored selected subgroups.

median follow-up of 89 months.
(Courneya et al. MSSE 2014;46:1744-51)
START Trial Events
(Courneya et al. MSSE 2014;46:1744-51)
Disease-Free Survival
8-year DFS was 82.7% for EX vs. 75.6% for UC
(Courneya et al. MSSE 2014;46:1744-51)
Overall Survival
8-year OS was 91.2% for EX vs. 82.7% for UC
(Courneya et al. MSSE 2014;46:1744-51)
Recurrence-Free Interval
8-year RFI was 12.6% for EX vs. 21.6% for UC
(Courneya et al. MSSE 2014;46:1744-51)
Disease-Free Survival by Subgroups
(Courneya et al. MSSE 2014;46:1744-51)
Possible Explanations

PA improved chemotherapy completion rate (although
strongest effect was with optimal chemotherapy dosing).

PA during chemotherapy may promote PA during
survivorship (6 month follow-up data not supportive).

PA may potentiate effects of chemotherapy:

drug distribution, pharmacodynamics, and metabolism,

nitric oxide-mediated peripheral blood flow, angiogenesis,
endogenous antioxidant expression.
(Courneya et al. MSSE 2014;46:1744-51)
Why Not a Randomized Trial?

no phase III randomized exercise trials with survival
endpoints are ongoing in early stage breast cancer.

Excellent survival rate >90% means that:

sample size is too large (several thousand).

length of intervention is too long (>5 years).

length of follow-up is too long (>10 years).

logistical and financial challenges.
Funded by the Canadian Institutes of Health Research.
AMBER Methods

prospective cohort design with breast cancer patients
being recruited soon after surgery.

sample size of 1500 Alberta breast cancer patients
diagnosed with stages I (T1c) to IIIc.

assessments at baseline (<90 days of surgery), 1 year
(after completion of primary therapy), 3 years (early
survivorship), and 5 years (mid survivorship).

5-10 year follow-up for disease outcomes.
(Courneya et al BMC Cancer 2012;12:525)
AMBER PA and HRF Measures

comprehensive self-report of PA and sedentary.

objective PA and sedentary (accelerometers).

maximal cardiorespiratory fitness (gas exchange).

maximal strength and endurance (8RM, SLT).

flexibility and balance.

body composition (DXA, anthropometrics).

lymphedema (perometers) and neuropathy.
(Courneya et al BMC Cancer 2012;12:525)
AMBER Update

accrual began July, 2012.

>600 patients accrued as of June, 2015.

estimated accrual completion in 2018.

250 patients with 1 year follow-up.

most common reason for ineligibility is <T1c.

most common reason for refusal is “overwhelmed”.
CHALLENGE Trial (CO.21)
Colon Health and Life-Long Exercise
Change (CHALLENGE) Trial (CO.21)

primary objective is to determine whether a 3 year structured
exercise program improves DFS in high risk stage II or III colon
cancer survivors 2-6 months after chemotherapy.

first exercise trial with a survival-related outcome as primary.

multinational in Canada (NCIC CTG) and Australia (SURG).

funded by NCIC-CTG and NHMRC in Australia.
(Courneya et al Curr Onc 2008;15:262-70)
CHALLENGE Trial Update

20 centers in Canada.

26 centers in Australia.

380 randomized.

US, Israel, Kor., France

UK expansion.

majority of patients are
adhering to program.

most improving fitness.
PA and Prostate Cancer Survival

830 men diagnosed with stage I-III prostate cancer
in 1997-2000 and followed until Oct. 2014.

PA assessed at diagnosis and every 2 years after
using the LTPAQ and converted to MET hours.

adjusted for disease and treatment variables as well
as diet and body mass index.

577 deaths; 236 prostate deaths; 401 recurrences.
(Friedenreich et al. submitted)
PA and Prostate Cancer Survival
(Friedenreich et al. submitted)
Physical Activity and Overall Survival
(Friedenreich et al. submitted)
Global Action Project (GAP4) Trial

phase III RCT to test the effects of exercise on overall
survival in prostate cancer patients with M1 CRPC.

multinational trial supported by Movember.

Study Co-Chairs: Fred Saad and Rob Newton.

currently finalizing protocol.

plan is to launch the trial in fall 2015.
GAP4 Trial

Patients: 860 M1 CRPC, ECOG 0-1, medical
clearance, not meeting EX guidelines (HR=0.78).

Intervention: tapered supervised EX for 9 months;
transition to home program for 15 months.

Comparison: no exercise; psychosocial support.

Outcomes: OS, PFS, PSA progression, skeletal
adverse events, pain, fatigue, QoL, mechanisms.
Healthy Exercise for Lymphoma
Patients (HELP) Trial

RCT comparing AET to UC in 122 lymphoma
patients receiving chemotherapy or off treatments.

12 weeks supervised exercise training.

primary endpoint TOI-An.

secondary endpoints of HRF, PROs, medical.
(Courneya et al. J Clin Onc 2009;27:4605-12)
Effects of Exercise on Chemotherapy
Completion Rate (n=54)
% Completion Rate
110
P=.45
P=.20
100
UC
AET
90
80
70
60
50
% of minimum
% of maximum
(Courneya et al. J Clin Onc 2009;27:4605-12)
Effects of Exercise on Treatment Response (n=54)
60
P=.24
UC
AET
% With Response
50
40
30
20
10
0
Stable
Partial
Complete
(Courneya et al. J Clin Onc 2009;27:4605-12)
HELP Trial Outcomes

patients randomized between 2005-2008.

electronic record review in summer 2013.

abstracted events, dates, and treatments.

explored progression-free survival (PFS).

adjusted analyses based on propensity scores.

ITT analyses and explored protocol adherence (crossover).

median follow-up of 61 months.
(Courneya et al. Can Causes Con 2015;26:269-76)
Progression-Free Survival
(Courneya et al. Can Causes Con 2015;26:269-76)
Progression-Free Survival
5-year PFS was 68.5% for SUP EX vs. 59.0% for No SUP EX
(HR=0.70, 95% CI=0.35-1.39, log rank p=0.31)
(Courneya et al. Can Causes Con 2015;26:269-76)
Optimal Exercise Prescription?
Optimal exercise prescription for improved cancer
outcomes is unknown, however:
 aerobic >
 volume
strength;
is important;
 some
better than none (biggest gains);
 more
is even better (diminishing returns);
 vigorous >
 avoiding
moderate;
sitting may also be important.
Summary and Conclusions

self-reported PA is associated with survival in
several cancer groups (breast, colon, prostate).

phase II data suggestive of possible survival benefit
of supervised exercise in breast and lymphoma.

phase III exercise trials ongoing in colon and
prostate cancer.

lifestyle trials ongoing in several cancer groups.

weight loss trials are also being pursued.
Acknowledgements
 Many
colleagues, students, staff and study
participants have contributed to this research.
 K.S.
Courneya is supported by the Canada
Research Chairs Program.