Physical-Based Therapeutic Approaches for Cancer-Related Pain Lee W. Jones, Ph.D Department of Surgery Duke University Medical Center 2 nd Annual Pain

Physical-Based Therapeutic Physical-Based Therapeutic Approaches for Cancer-Related Approaches for Cancer-Related

PainPain

Physical-Based Therapeutic Physical-Based Therapeutic Approaches for Cancer-Related Approaches for Cancer-Related

PainPain

Lee W. Jones, Ph.DLee W. Jones, Ph.DLee W. Jones, Ph.DLee W. Jones, Ph.DDepartment of SurgeryDepartment of Surgery

Duke University Medical CenterDuke University Medical Center

22ndnd Annual Pain Management Symposium Annual Pain Management SymposiumJune 6June 6thth, 2008, 2008

Department of SurgeryDepartment of SurgeryDuke University Medical CenterDuke University Medical Center

22ndnd Annual Pain Management Symposium Annual Pain Management SymposiumJune 6June 6thth, 2008, 2008

Presentation OutlinePresentation Outline

• Brief Overview of Cancer-Related Pain Brief Overview of Cancer-Related Pain (CRP)(CRP)

• Management of CRPManagement of CRP

• Role of Physical-Based Approaches for Role of Physical-Based Approaches for CRPCRP

• Future Directions Future Directions

• Brief Overview of Cancer-Related Pain Brief Overview of Cancer-Related Pain (CRP)(CRP)

• Management of CRPManagement of CRP

• Role of Physical-Based Approaches for Role of Physical-Based Approaches for CRPCRP

• Future Directions Future Directions

Brief Overview of CRPBrief Overview of CRP

Overview of CRPOverview of CRP• 30% to 50% undergoing therapy30% to 50% undergoing therapy

• 70% to 90% advanced disease70% to 90% advanced disease

• Bone pain most common (>75% related Bone pain most common (>75% related to neoplastic invasion)to neoplastic invasion)

• CRP SyndromesCRP Syndromes

• NociceptionNociception - damage to pain - damage to pain receptorsreceptors

• NeuropathicNeuropathic - nerve damage - nerve damage (peripheral neuropathy)(peripheral neuropathy)

• Treatment-related painTreatment-related pain – damage to – damage to receptors by Sx, RT, CT, & ETreceptors by Sx, RT, CT, & ET

• 30% to 50% undergoing therapy30% to 50% undergoing therapy

• 70% to 90% advanced disease70% to 90% advanced disease

• Bone pain most common (>75% related Bone pain most common (>75% related to neoplastic invasion)to neoplastic invasion)

• CRP SyndromesCRP Syndromes

• NociceptionNociception - damage to pain - damage to pain receptorsreceptors

• NeuropathicNeuropathic - nerve damage - nerve damage (peripheral neuropathy)(peripheral neuropathy)

• Treatment-related painTreatment-related pain – damage to – damage to receptors by Sx, RT, CT, & ETreceptors by Sx, RT, CT, & ET

The Symptom ClusterThe Symptom Cluster

PAINPAIN

FATIGUEFATIGUE

DISTRESSDISTRESS

FUNCTIONFUNCTIONDECLINEDECLINE

QOLQOL

Management of CRPManagement of CRP

Management of CRPManagement of CRP

Pharmacologic ApproachesPharmacologic Approaches

• Opoids / Analgesics / NSAIDs Opoids / Analgesics / NSAIDs

• Bisphosphonates / new approachesBisphosphonates / new approaches

• Inadequate pain reliefInadequate pain relief

• Not benign (GI toxicity / cog Not benign (GI toxicity / cog dysfunction)dysfunction)

Pharmacologic ApproachesPharmacologic Approaches

• Opoids / Analgesics / NSAIDs Opoids / Analgesics / NSAIDs

• Bisphosphonates / new approachesBisphosphonates / new approaches

• Inadequate pain reliefInadequate pain relief

• Not benign (GI toxicity / cog Not benign (GI toxicity / cog dysfunction)dysfunction)

Non-Pharmacologic ApproachesNon-Pharmacologic Approaches

• Surgery / psychological (grp Surgery / psychological (grp psychotherapy / stress management, psychotherapy / stress management, etc.)etc.)

• Address physical dimensions??Address physical dimensions??

Non-Pharmacologic ApproachesNon-Pharmacologic Approaches

• Surgery / psychological (grp Surgery / psychological (grp psychotherapy / stress management, psychotherapy / stress management, etc.)etc.)

• Address physical dimensions??Address physical dimensions??

Role of Physical-Based Approaches for CRP

Role of Physical-Based Approaches for CRP

Types of Physical-Based Approaches

Types of Physical-Based Approaches

• YogaYoga

• mediation, gentle postures, breathing mediation, gentle postures, breathing exercises exercises

• Tai ChiTai Chi

• Meditative form of exercise & postures Meditative form of exercise & postures

• Structured Exercise TrainingStructured Exercise Training

• Bodily activity aim of improving fitness & Bodily activity aim of improving fitness & healthhealth

• Physical / Rehabilitation TherapyPhysical / Rehabilitation Therapy

• Prevention, management, & tx of Prevention, management, & tx of movement disordersmovement disorders

• YogaYoga

• mediation, gentle postures, breathing mediation, gentle postures, breathing exercises exercises

• Tai ChiTai Chi

• Meditative form of exercise & postures Meditative form of exercise & postures

• Structured Exercise TrainingStructured Exercise Training

• Bodily activity aim of improving fitness & Bodily activity aim of improving fitness & healthhealth

• Physical / Rehabilitation TherapyPhysical / Rehabilitation Therapy

• Prevention, management, & tx of Prevention, management, & tx of movement disordersmovement disorders

Review of LiteratureReview of Literature

• >50% of exercise studies conducted in >50% of exercise studies conducted in

early-stage breast cancer patientsearly-stage breast cancer patients

• >50% completed during treatment>50% completed during treatment

• Majority tested aerobic-based interventionsMajority tested aerobic-based interventions

• Cycle ergometry/treadmill walking Cycle ergometry/treadmill walking

• 3d.wk for 6-24 weeks, moderate intensity3d.wk for 6-24 weeks, moderate intensity

• >50% of exercise studies conducted in >50% of exercise studies conducted in

early-stage breast cancer patientsearly-stage breast cancer patients

• >50% completed during treatment>50% completed during treatment

• Majority tested aerobic-based interventionsMajority tested aerobic-based interventions

• Cycle ergometry/treadmill walking Cycle ergometry/treadmill walking

• 3d.wk for 6-24 weeks, moderate intensity3d.wk for 6-24 weeks, moderate intensity

• Adherence levels (if reported) > 70%Adherence levels (if reported) > 70%• Adherence levels (if reported) > 70%Adherence levels (if reported) > 70%

Jones & Demark-Wahnefried. Lancet Oncol 2007

Review of LiteratureReview of Literature

• All reported significant benefits

• No adverse events

• Multiple Biopsychosocial Outcomes

• All reported significant benefits


• Multiple Biopsychosocial Outcomes

Physiologic Outcomes – exercise capacity, body comp, NK activity, flexibility

Physiologic Outcomes – exercise capacity, body comp, NK activity, flexibility

Tx-Related Symptoms – fatigue, pain, nausea, diarrhea, platelet transfusion, hospital stayTx-Related Symptoms – fatigue, pain, nausea, diarrhea, platelet transfusion, hospital stay

QOL Outcomes – overall, PWB, FWB, SWB, SWL, anx/depQOL Outcomes – overall, PWB, FWB, SWB, SWL, anx/dep

Jones & Demark-Wahnefried. Lancet Oncol 2007

Prior WorkPrior Work• Examined potential role of exercise in the Examined potential role of exercise in the

following:following:

DescriptiveDescriptive InterventionIntervention

Early-Stage Breast Cancer Early-Stage Breast Cancer Metastatic BreastMetastatic Breast

Non-Hodgkins LymphomaNon-Hodgkins Lymphoma Inoperable NSCLCInoperable NSCLC

Multiple MyelomaMultiple Myeloma Preoperative Preoperative NSCLCNSCLC

Primary Brain CancerPrimary Brain Cancer Neoadjuvant Neoadjuvant BreastBreast

EndometrialEndometrial Adjuvant NSCLCAdjuvant NSCLC

ColorectalColorectal Anemic Cancer Anemic Cancer PtsPts

ProstateProstate NHL NHL

• Examined potential role of exercise in the Examined potential role of exercise in the following:following:

DescriptiveDescriptive InterventionIntervention

Early-Stage Breast Cancer Early-Stage Breast Cancer Metastatic BreastMetastatic Breast

Non-Hodgkins LymphomaNon-Hodgkins Lymphoma Inoperable NSCLCInoperable NSCLC

Multiple MyelomaMultiple Myeloma Preoperative Preoperative NSCLCNSCLC

Primary Brain CancerPrimary Brain Cancer Neoadjuvant Neoadjuvant BreastBreast

EndometrialEndometrial Adjuvant NSCLCAdjuvant NSCLC

ColorectalColorectal Anemic Cancer Anemic Cancer PtsPts

ProstateProstate NHL NHL

Prior Clinical TrialsPrior Clinical TrialsPrior Clinical TrialsPrior Clinical Trials

REHAB TrialREHAB Trial

• Examined the effects of endurance training on exercise capacity, QOL, & biologic outcomes in PM breast cancer survivors

• Examined the effects of endurance training on exercise capacity, QOL, & biologic outcomes in PM breast cancer survivors

Courneya, Jones et al. Courneya, Jones et al. JCO JCO 20032003

Aims

• Effects on QOL (FACT-B) and exercise capacity

(VO2peak)

• Effects on metabolic hormones (insulin, IGF-1, IGFBPs), & CV risk factors (BP, CRP, etc.)

Aims

• Effects on QOL (FACT-B) and exercise capacity

(VO2peak)

• Effects on metabolic hormones (insulin, IGF-1, IGFBPs), & CV risk factors (BP, CRP, etc.)

REHAB Trial

MethodREHAB Trial

MethodPatients and Eligibility

• Histologically confirmed (stage I-IIIa) breast cancer

• No evidence of metastatic or recurrent disease

• Completion of primary adjuvant therapy

• Postmenopausal

• No significant or recent CV disease

• Recruitment letter sent to all potentially eligible participants following physician approval

Patients and Eligibility

• Histologically confirmed (stage I-IIIa) breast cancer

• No evidence of metastatic or recurrent disease

• Completion of primary adjuvant therapy

• Postmenopausal


• Recruitment letter sent to all potentially eligible participants following physician approval


REHAB Trial

Patient CharacteristicsREHAB Trial

Patient CharacteristicsAll Cases

n=53Exercise

n=24Control

n=28

Mean / % Mean / % Mean / %

Mean Age (yrs) 59 59 58

BMI (kg/m2) 29 29 29

Stage I 40% 42% 39%

Chemotherapy 40% 42% 39%

Radiotherapy 71% 67% 75%

Endocrine 46% 46% 46%


REHAB Trial

Results – Exercise Capacity - ITTREHAB Trial

Results – Exercise Capacity - ITT

10

15

20

25

30

VO

2 (mL.kg.min)

Baseline 15 weeks

EGCG

2.7 mL.kg.min within group ( 17.4%) (p<.001)3.4 mL.kg.min between groups


REHAB Trial

Results – QOLREHAB Trial

Results – QOL

100

105

110

115

120

125

FACT-B (0-140)

Baseline 15 weeks

EG

CG

+9.1 points within group (clinically meaningful) (p<.001)+8.8 between groups


REHAB Trial

Results – FatigueREHAB Trial

Results – Fatigue

5

10

15

20

FACT - Fatigue (0-52)

Baseline 15 weeks

EG

CG

-9.3 points within group (clinically meaningful) (p<.006)-7.3 between groups

EG fatigue (adjusted analyses)


REHAB Trial

Other ResultsREHAB Trial

Other ResultsMetabolic Hormones (Fairey et al. CEBP, 2003)

• No differences in fasting insulin, glucose, insulin resistance, or IGFBP-1

• Differences in IGF-1 & IGFBP-3

Metabolic Hormones (Fairey et al. CEBP, 2003)

• No differences in fasting insulin, glucose, insulin resistance, or IGFBP-1

• Differences in IGF-1 & IGFBP-3

CVD Risk Factors (Fairey et al. Brain Behav Immun 2005)

• Non-significant reductions in CRP ( 1.39 mg/L)

• Non-significant reductions in SBP ( 5.5 mm Hg), DBP ( 3.6 mm Hg), & HDL-C ( 0.05 mmol/L)

CVD Risk Factors (Fairey et al. Brain Behav Immun 2005)

• Non-significant reductions in CRP ( 1.39 mg/L)

• Non-significant reductions in SBP ( 5.5 mm Hg), DBP ( 3.6 mm Hg), & HDL-C ( 0.05 mmol/L)

EXTRA TrialEXTRA Trial

• Determine if a 12-week endurance exercise training program can improve QOL in anemic pts receiving Aranesp

• Determine if a 12-week endurance exercise training program can improve QOL in anemic pts receiving Aranesp

Sponsored by Amgen Inc,

Aims

• Effects on QOL (FACT-An), fatigue,

exercise capacity (VO2peak)

• Effects on Hb response & dosing requirement

Aims

• Effects on QOL (FACT-An), fatigue,

exercise capacity (VO2peak)

• Effects on Hb response & dosing requirement

EXTRA Trial

MethodEXTRA Trial

MethodPatients and Eligibility

• Histologically confirmed solid tumors

• Hb level between 80 & 110 g/L

• Expected survival ≥3 months


• Identified via central screening


• Histologically confirmed solid tumors

• Hb level between 80 & 110 g/L

• Expected survival ≥3 months


• Identified via central screening

EXTRA Trial

Participant CharacteristicsEXTRA Trial

Participant Characteristics

All Casesn=55

DA Alonen=29

DA+EX n=26

Mean / % Mean / % Mean / %

Mean Age (yrs) 56 54 58

Breast Cancer Dx 60% 62% 58%

Stage IV 47% 38% 57%

Chemotherapy 92% 90% 96%

Prior transfusion 20% 24% 15%

Heart Disease 16% 17% 14%

EXTRA Trial

Results – Exercise Capacity - ITTEXTRA Trial

Results – Exercise Capacity - ITT

10

15

20

25

30

VO

2 (mL.kg.min)

Baseline 12 weeks

DA+EXDAL

3.5 mL.kg.min within group ( 22%) (p<.001)3.0 mL.kg.min between groups

Courneya, Jones et al. Courneya, Jones et al. JCO JCO SubmittedSubmitted

EXTRA Trial

Results – QOLEXTRA Trial

Results – QOL

115

120

125

130

135

140

145

150

FACT-An (0-188)

Baseline 12 weeks

DA+EX

DAL

+13.4 points within group (clinically meaningful) (p=.637)-6.9 between groups

Courneya, Jones et al. Courneya, Jones et al. JCO JCO SubmittedSubmitted

EXTRA Trial

Results – Hb OutcomesEXTRA Trial

Results – Hb Outcomes

NSCLC Pre-Op StudyNSCLC Pre-Op Study

• Determine the feasibility of pre-operative exercise training for patients undergoing surgical resection for NSCLC

• Determine the feasibility of pre-operative exercise training for patients undergoing surgical resection for NSCLC

Aims

• Determine feasibility of exercise training

• Determine the effects of exercise training on exercise capacity, QoL, & biologic outcomes

Aims


• Determine the effects of exercise training on exercise capacity, QoL, & biologic outcomes

Jones et al. Cancer 2007


Pre-Op Study

MethodsPre-Op Study

Methods


• Suspected stage I-IIIa NSCLC with or without preoperative histologic confirmation

• Surgery for curative intent

• No contraindications to CPET


• Suspected stage I-IIIa NSCLC with or without preoperative histologic confirmation

• Surgery for curative intent

• No contraindications to CPET

Pre-Op

Patient FlowPre-Op

Patient Flow

Number of Patients ScreenedNumber of Patients ScreenedN=43N=43

Number of Patients EligibleNumber of Patients EligibleN=35 (35/43 = 81%)N=35 (35/43 = 81%)

Baseline Tests CompletedBaseline Tests CompletedN=25 (25/35 = 71%)N=25 (25/35 = 71%)

Patients Becoming IneligiblePatients Becoming IneligibleN=5 (5/25 = 20%)N=5 (5/25 = 20%)

Pre-Surgery Tests CompletedPre-Surgery Tests CompletedN=18 (18/20 = 90%)N=18 (18/20 = 90%)

Post-Surgery Tests CompletedPost-Surgery Tests CompletedN=13 (13/18 = 72%)N=13 (13/18 = 72%)

Reasons for Non-Eligibility (n=8)Reasons for Non-Eligibility (n=8)

Geographical Location (n=6)Geographical Location (n=6)

Reasons for Non-Consent (n=10)Reasons for Non-Consent (n=10)

Not Interested (n=6)Not Interested (n=6)

Reasons for Drop Out (n=2)Reasons for Drop Out (n=2)

No transportation (n=1)No transportation (n=1)Work Commitments (n=1)Work Commitments (n=1)

Reasons for Drop Out (n=5)Reasons for Drop Out (n=5)Died (n=2)Died (n=2)Sx complicationsSx complications

Reasons for Non-Eligibility (n=5)Reasons for Non-Eligibility (n=5)

Became inoperable (n=4)Became inoperable (n=4)



Pre-Op Study

Participant Characteristics (n=20)Pre-Op Study

Participant Characteristics (n=20)No. %

Age, mean - yrs 65±10

Male, % 6 30

BMI, mean 27±4

NSCLC Diagnosis 13 65

Lobectomy 15 75

FEV1, Liters 1.9±0.6 (73%)

VO2peak, mL.kg.min-1 15.7±3.6 (70%)

6MWD, meters 427±89 (68%)

Pre-Op Study

Results – VO2peak -ITTPre-Op Study

Results – VO2peak -ITT

10

12

14

16

18

20

VO

2 (mL.kg.min)

Baseline Pre-Surgery

2.4mL.kg.min ( 15%) (p=.002)


Pre-Op Study

Results – VO2peak (adherence)Pre-Op Study

Results – VO2peak (adherence)

10

12

14

16

18

20

VO

2 (mL.kg.min)

Baseline Pre-Surgery

>80%

<80%

≥80% adherence: 3.3mL.kg.min ( 20%) (p=.006)

<80% adherence: 0.8mL.kg.min ( 5%) (p=.129)


Pre-Op Study

Results – VO2peak (n=13)Pre-Op Study

Results – VO2peak (n=13)


10

12

14

16

18

20

VO

2 (mL.kg.min)

Baseline Pre-Surgery Post-surgery

18% 18%

~0%

Current Clinical TrialsCurrent Clinical TrialsCurrent Clinical TrialsCurrent Clinical Trials

Duke InfrastructureDuke InfrastructureDuke InfrastructureDuke InfrastructureExercise TrainingExercise TrainingExercise TrainingExercise Training

Exercise TestingExercise TestingExercise TestingExercise Testing

• Determine the feasibility of exercise training among 20 postsurgical NSCLC patients

• Determine the feasibility of exercise training among 20 postsurgical NSCLC patients

Funded by the Lance Armstrong Foundation

Aims


• Determine the effects of exercise training on exercise capacity, tx completion rates, toxicity & QoL

• Cycle ergometry (3x/wk for 20-45mins, 60-

100% VO2peak) for 14 weeks

• N=20 patients recruited; 19 completed; 1 on study

Aims


• Determine the effects of exercise training on exercise capacity, tx completion rates, toxicity & QoL

• Cycle ergometry (3x/wk for 20-45mins, 60-

100% VO2peak) for 14 weeks

• N=20 patients recruited; 19 completed; 1 on study

Jones LW, Crawford J, Garst J, Kraus WE, Peterson B

NSCLC Post-Op StudyNSCLC Post-Op Study

NSCLC Post-Op Preliminary ResultsNSCLC Post-Op Preliminary Results

• 79% adherence

• 2 drop out (10%)

• Baseline - 15.3 ml.kg.min (30% age-matched predicted)

• Postintervention – 16 ml.kg.min ( 7%)


• Abstract submitted to ASCO

• 79% adherence

• 2 drop out (10%)

• Baseline - 15.3 ml.kg.min (30% age-matched predicted)

• Postintervention – 16 ml.kg.min ( 7%)


• Abstract submitted to ASCO

• Effects of exercise training on tumor response Effects of exercise training on tumor response

to chemotherapy among 20 breast cancer to chemotherapy among 20 breast cancer

patients undergoing neoadjuvant patients undergoing neoadjuvant

chemotherapychemotherapy

• Effects of exercise training on tumor response Effects of exercise training on tumor response

to chemotherapy among 20 breast cancer to chemotherapy among 20 breast cancer

patients undergoing neoadjuvant patients undergoing neoadjuvant

chemotherapychemotherapy

Sponsored by US DOD Breast Cancer Research Program

AimsAims

• Effects of exercise on exercise capacityEffects of exercise on exercise capacity

• Examine effects of exercise on tumor Examine effects of exercise on tumor

physiology, tx response, QoL, cardiac function, physiology, tx response, QoL, cardiac function,

& blood markers& blood markers

• Cycle ergometry (3x/wk, 30-45mins, 60-100% Cycle ergometry (3x/wk, 30-45mins, 60-100%

VOVO2peak2peak for 12 weeks) for 12 weeks)

• 6 patients completed; 4 on study6 patients completed; 4 on study

AimsAims

• Effects of exercise on exercise capacityEffects of exercise on exercise capacity

• Examine effects of exercise on tumor Examine effects of exercise on tumor

physiology, tx response, QoL, cardiac function, physiology, tx response, QoL, cardiac function,

& blood markers& blood markers

• Cycle ergometry (3x/wk, 30-45mins, 60-100% Cycle ergometry (3x/wk, 30-45mins, 60-100%

VOVO2peak2peak for 12 weeks) for 12 weeks)

• 6 patients completed; 4 on study6 patients completed; 4 on study

Jones LWJones LW, Marcom PK, Dewhirst, M, Blackwell K, Allen J, Douglas PD, Kraus WE, , Marcom PK, Dewhirst, M, Blackwell K, Allen J, Douglas PD, Kraus WE, Peterson, BPeterson, B

Breast Neoadjuvant StudyBreast Neoadjuvant Study

• To prospectively assess changes in exercise To prospectively assess changes in exercise

capacity and skeletal muscle function across capacity and skeletal muscle function across

primary brain tumor therapy (n=25 HGG; n=10 primary brain tumor therapy (n=25 HGG; n=10

LG)LG)

• Baseline (pre chemo/XRT; 6 weeks; 6 months)Baseline (pre chemo/XRT; 6 weeks; 6 months)

• To prospectively assess changes in exercise To prospectively assess changes in exercise

capacity and skeletal muscle function across capacity and skeletal muscle function across

primary brain tumor therapy (n=25 HGG; n=10 primary brain tumor therapy (n=25 HGG; n=10

LG)LG)

• Baseline (pre chemo/XRT; 6 weeks; 6 months)Baseline (pre chemo/XRT; 6 weeks; 6 months)

Funded by NCI – R03

AimsAims

• Examine Examine feasibilityfeasibility of exercise capacity & skeletal of exercise capacity & skeletal

muscle function assessmentsmuscle function assessments

• Assess Assess changeschanges in these outcomes & QOL in these outcomes & QOL

• Disease progression & overall survivalDisease progression & overall survival

AimsAims

• Examine Examine feasibilityfeasibility of exercise capacity & skeletal of exercise capacity & skeletal

muscle function assessmentsmuscle function assessments

• Assess Assess changeschanges in these outcomes & QOL in these outcomes & QOL

• Disease progression & overall survivalDisease progression & overall survival

Jones LWJones LW, Reardon D, Friedman HS, Friedman A, Major N, Kraus WE, , Reardon D, Friedman HS, Friedman A, Major N, Kraus WE, Peterson BPeterson B

Glioma Profiling StudyGlioma Profiling Study

AssessmentsAssessments

• Exercise CapacityExercise Capacity• Exercise CapacityExercise Capacity

• Skeletal Muscle FunctionSkeletal Muscle Function

• Muscle sizeMuscle size

• Muscle strengthMuscle strength

• Skeletal Muscle FunctionSkeletal Muscle Function

• Muscle sizeMuscle size

• Muscle strengthMuscle strength

• Body CompositionBody Composition• Body CompositionBody Composition

Preliminary ResultsPreliminary Results

• 105 screened; 50 (48%) eligible; 24 (48%) recruited

• 16 HGG; 8 LG

• N=24 completed baseline; n=20 completed 6 week assessment; n=7 completed 6 month

• 2 pts loss to follow-up (deceased, DVT)

• Baseline exercise capacity = 15.45 mL.kg.min (~45% below age-sex predicted)

• 6 week = 15.74 mL.kg.min

• 105 screened; 50 (48%) eligible; 24 (48%) recruited

• 16 HGG; 8 LG

• N=24 completed baseline; n=20 completed 6 week assessment; n=7 completed 6 month

• 2 pts loss to follow-up (deceased, DVT)

• Baseline exercise capacity = 15.45 mL.kg.min (~45% below age-sex predicted)

• 6 week = 15.74 mL.kg.min

Forthcoming StudiesForthcoming StudiesForthcoming StudiesForthcoming Studies

Pre-Clinical InvestigationsPre-Clinical InvestigationsPre-Clinical InvestigationsPre-Clinical Investigations

• Determine the effects of exercise training Determine the effects of exercise training

on antitumor efficacy of doxorubicin (DOX) on antitumor efficacy of doxorubicin (DOX)

in MDA-MB-231 breast cancer xenograftsin MDA-MB-231 breast cancer xenografts

• Funded by US Dept of Defense BCRP - Funded by US Dept of Defense BCRP -

Concept AwardConcept Award

• Determine the effects of exercise training Determine the effects of exercise training

on antitumor efficacy of doxorubicin (DOX) on antitumor efficacy of doxorubicin (DOX)

in MDA-MB-231 breast cancer xenograftsin MDA-MB-231 breast cancer xenografts

• Funded by US Dept of Defense BCRP - Funded by US Dept of Defense BCRP -

Concept AwardConcept Award

Exercise/Chemotherapy InteractionExercise/Chemotherapy Interaction

PurposePurposeExercise/Chemotherapy InteractionExercise/Chemotherapy Interaction

PurposePurposeJones LW, Eves ND, Courneya KS, Baracos VE, Hanson J, & Mackey JR

MethodMethod

Athymic FemaleAthymic FemaleHSD Mice (3-4wks)HSD Mice (3-4wks)

N = 84N = 84

All Mice S.C. All Mice S.C. Implanted MDA-Implanted MDA-MB-231 (5x10MB-231 (5x1066))

Acclimatization Acclimatization for 10 Daysfor 10 Days

Doxorubicin Only Doxorubicin Only (n=21)(n=21)

R

Exercise Only Exercise Only (n=21)(n=21)

Exercise + Exercise + Doxorubicin Doxorubicin

(n=21)(n=21)

No Intervention No Intervention Control (n=21)Control (n=21)

Tumor Tumor Establishment for Establishment for

14 Days14 Days

Exercise InterventionExercise InterventionExercise InterventionExercise Intervention

• Forced running on Treadmill (6 chambers)Forced running on Treadmill (6 chambers)

• 2nd treadmill ‘sham exercise training’2nd treadmill ‘sham exercise training’

• 18m/min @ 0% grade for 45 mins, 5d.wk, 8 wks18m/min @ 0% grade for 45 mins, 5d.wk, 8 wks

• 70-75% VO70-75% VO2max2max

• Forced running on Treadmill (6 chambers)Forced running on Treadmill (6 chambers)

• 2nd treadmill ‘sham exercise training’2nd treadmill ‘sham exercise training’

• 18m/min @ 0% grade for 45 mins, 5d.wk, 8 wks18m/min @ 0% grade for 45 mins, 5d.wk, 8 wks

• 70-75% VO70-75% VO2max2max

ResultsResults

0

10

20

30

40

50

60

70

80

90

100

6 12 18 24 30 36 42 48 54

% S

urv

ivin

g

% S

urv

ivin

g

DaysDays

Control Control N=21N=21 Events=14Events=14 Median Growth Delay=25 Median Growth Delay=25

Ex Only Ex Only N=21N=21 Events=16Events=16 Median Growth Delay=25 Median Growth Delay=25

Ex + CTEx + CT N=21N=21 Events=16Events=16 Median Growth Delay=36 (>C0 p=0.029; Ex Median Growth Delay=36 (>C0 p=0.029; Ex Only p=0.080)Only p=0.080)CT Only CT Only N=21N=21 Events=13Events=13 Median Growth Delay=42 (>C0 p=0.0084; Ex Median Growth Delay=42 (>C0 p=0.0084; Ex Only p=0.029)Only p=0.029)

Log Rank P=0.015Log Rank P=0.015

35%35%

20%20%

16%16%

DiscussionDiscussion

• Moderate intensity TM running does not Moderate intensity TM running does not

significantly influence DOX-induced tumor significantly influence DOX-induced tumor

growth delay in MDA-MB-231 xenograftsgrowth delay in MDA-MB-231 xenografts

• Trend for longer survival in DOX only suggests Trend for longer survival in DOX only suggests

that TM running may partially inhibit the that TM running may partially inhibit the

efficacy of DOX therapyefficacy of DOX therapy

• Clinical trial underway (DOD funded study)Clinical trial underway (DOD funded study)

• Moderate intensity TM running does not Moderate intensity TM running does not

significantly influence DOX-induced tumor significantly influence DOX-induced tumor

growth delay in MDA-MB-231 xenograftsgrowth delay in MDA-MB-231 xenografts

• Trend for longer survival in DOX only suggests Trend for longer survival in DOX only suggests

that TM running may partially inhibit the that TM running may partially inhibit the

efficacy of DOX therapyefficacy of DOX therapy

• Clinical trial underway (DOD funded study)Clinical trial underway (DOD funded study)

SummarySummary

Growing interest in role of exercise for Growing interest in role of exercise for cancer survivorscancer survivorsGrowing interest in role of exercise for Growing interest in role of exercise for cancer survivorscancer survivors

Preliminary evidence – safe, feasible, & Preliminary evidence – safe, feasible, & beneficial supportive interventionbeneficial supportive interventionPreliminary evidence – safe, feasible, & Preliminary evidence – safe, feasible, & beneficial supportive interventionbeneficial supportive intervention

Current/forthcoming research addressing Current/forthcoming research addressing fundamental questionsfundamental questionsCurrent/forthcoming research addressing Current/forthcoming research addressing fundamental questionsfundamental questions

Integral part of comprehensive cancer Integral part of comprehensive cancer carecareIntegral part of comprehensive cancer Integral part of comprehensive cancer carecare

Documents

Physical-Based Therapeutic Approaches for Cancer-Related Pain Lee W. Jones, Ph.D Department of Surgery Duke University Medical Center 2 nd Annual Pain