Student Submission -- Gen Psych Different Therapeutic Approaches
Physical-Based Therapeutic Approaches for Cancer-Related Pain
Transcript of Physical-Based Therapeutic Approaches for Cancer-Related Pain
Physical-Based Therapeutic Physical-Based Therapeutic Approaches for Cancer-Related PainApproaches for Cancer-Related Pain
Lee 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
Presentation Outline
• Brief Overview of Cancer-Related Pain (CRP)Brief Overview of Cancer-Related Pain (CRP)• Management of CRPManagement of CRP• Role of Physical-Based Approaches for CRPRole of Physical-Based Approaches for CRP• Future Directions Future Directions
Brief Overview of CRP
Overview 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 to Bone pain most common (>75% related to
neoplastic invasion)neoplastic invasion)• CRP SyndromesCRP Syndromes
• NociceptionNociception - damage to pain receptors - damage to pain receptors• NeuropathicNeuropathic - nerve damage (peripheral - nerve damage (peripheral
neuropathy)neuropathy)• Treatment-related painTreatment-related pain – damage to – damage to
receptors by Sx, RT, CT, & ETreceptors by Sx, RT, CT, & ET
The Symptom Cluster
PAINPAIN
FATIGUEFATIGUE
DISTRESSDISTRESS
FUNCTIONFUNCTIONDECLINEDECLINE
↓↓↓↓ QOLQOL
Management of CRP
Management of CRPPharmacologic ApproachesPharmacologic Approaches
• Opoids / Analgesics / NSAIDs Opoids / Analgesics / NSAIDs • Bisphosphonates / new approachesBisphosphonates / new approaches• Inadequate pain reliefInadequate pain relief• Not benign (GI toxicity / cog dysfunction)Not benign (GI toxicity / cog dysfunction)
Non-Pharmacologic ApproachesNon-Pharmacologic Approaches• Surgery / psychological (grp Surgery / psychological (grp
psychotherapy / stress management, etc.)psychotherapy / stress management, etc.)• Address physical dimensions??Address physical dimensions??
Role of Physical-Based Approaches for CRP
Types of Physical-Based Approaches• YogaYoga
• mediation, gentle postures, breathing exercises mediation, gentle postures, breathing 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 & healthBodily activity aim of improving fitness & health• Physical / Rehabilitation TherapyPhysical / Rehabilitation Therapy
• Prevention, management, & tx of movement Prevention, management, & tx of movement disordersdisorders
Review of Literature
• >50% of exercise studies conducted in early-stage >50% of exercise studies conducted in early-stage breast cancer patientsbreast 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%
Jones & Demark-Wahnefried. Lancet Oncol 2007
Review of Literature• All reported significant benefits• No adverse events
• Multiple Biopsychosocial Outcomes
Physiologic Outcomes – exercise capacity, 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
Jones & Demark-Wahnefried. Lancet Oncol 2007
Prior Work• Examined potential role of exercise in the following:Examined potential role of exercise in the 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 NSCLCPreoperative NSCLC
Primary Brain CancerPrimary Brain Cancer Neoadjuvant BreastNeoadjuvant Breast
EndometrialEndometrial Adjuvant NSCLCAdjuvant NSCLC
ColorectalColorectal Anemic Cancer PtsAnemic Cancer Pts
ProstateProstate NHL NHL
Prior Clinical TrialsPrior Clinical Trials
REHAB Trial• 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.)
REHAB 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
Courneya, Jones et al. Courneya, Jones et al. JCO JCO 20032003
REHAB 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%
Courneya, Jones et al. Courneya, Jones et al. JCO JCO 20032003
REHAB Trial
Results – Exercise Capacity - ITT
10
15
20
25
30
VO2 (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
Courneya, Jones et al. Courneya, Jones et al. JCO JCO 20032003
REHAB Trial
Results – QOL
100
105
110
115
120
125
FACT-B (0-140)
Baseline 15 weeks
EGCG
+9.1 points within group (clinically meaningful) (p<.001)+8.8 between groups
Courneya, Jones et al. Courneya, Jones et al. JCO JCO 20032003
REHAB Trial
Results – Fatigue
5
10
15
20
FACT - Fatigue (0-52)
Baseline 15 weeks
EGCG
-9.3 points within group (clinically meaningful) (p<.006)-7.3 between groups
EG ↑ fatigue (adjusted analyses)
Courneya, Jones et al. Courneya, Jones et al. JCO JCO 20032003
REHAB 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
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 Trial• 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
EXTRA Trial
MethodPatients and Eligibility
• Histologically confirmed solid tumors
• Hb level between 80 & 110 g/L
• Expected survival ≥3 months
• No significant or recent CV disease
• Identified via central screening
EXTRA 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 - ITT
10
15
20
25
30
VO2 (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 – QOL
115
120
125
130
135
140
145
150
FACT-An (0-188)
Baseline 12 weeks
DA+ EXDAL
+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 Outcomes
NSCLC Pre-Op Study
• 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
Jones et al. Cancer 2007
Jones et al. Cancer 2007
Pre-Op Study
MethodsPatients and Eligibility
• Suspected stage I-IIIa NSCLC with or without preoperative histologic confirmation
• Surgery for curative intent
• No contraindications to CPET
Pre-Op
Patient FlowNumber of Patients ScreenedNumber of Patients Screened
N=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)
Jones et al. Cancer 2007
Jones et al. Cancer 2007
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 -ITT
10
12
14
16
18
20
VO2 (mL.kg.min)
Baseline Pre-Surgery
2.4mL.kg.min (↑ 15%) (p=.002)
Jones et al. Cancer 2007
Pre-Op Study
Results – VO2peak (adherence)
10
12
14
16
18
20
VO2 (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)
Jones et al. Cancer 2007
Pre-Op Study
Results – VO2peak (n=13)
Jones et al. Cancer 2007
10
12
14
16
18
20
VO2 (mL.kg.min)
Baseline Pre-Surgery Post-surgery
↑ 18% ↓ 18%
~0%
Current Clinical TrialsCurrent Clinical Trials
Duke InfrastructureDuke InfrastructureExercise TrainingExercise Training
Exercise TestingExercise Testing
• Determine the feasibility of exercise training among 20 postsurgical NSCLC patients
Funded by the Lance Armstrong Foundation
Aims
• Determine feasibility of exercise training
• 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 Study
NSCLC 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%)
• No adverse events
• Abstract submitted to ASCO
• Effects of exercise training on tumor response to Effects of exercise training on tumor response to chemotherapy among 20 breast cancer patients chemotherapy among 20 breast cancer patients undergoing neoadjuvant chemotherapyundergoing neoadjuvant chemotherapy
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 physiology, tx Examine effects of exercise on tumor physiology, tx response, QoL, cardiac function, & blood markersresponse, QoL, cardiac function, & blood markers
• Cycle ergometry (3x/wk, 30-45mins, 60-100% VOCycle ergometry (3x/wk, 30-45mins, 60-100% VO2peak2peak 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, Peterson, , Marcom PK, Dewhirst, M, Blackwell K, Allen J, Douglas PD, Kraus WE, Peterson, BB
Breast Neoadjuvant Study
• To prospectively assess changes in exercise capacity To prospectively assess changes in exercise capacity and skeletal muscle function across primary brain and skeletal muscle function across primary brain tumor therapy (n=25 HGG; n=10 LG)tumor therapy (n=25 HGG; n=10 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 muscle of exercise capacity & skeletal muscle function assessmentsfunction 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, Peterson , Reardon D, Friedman HS, Friedman A, Major N, Kraus WE, Peterson BB
Glioma Profiling Study
Assessments
• Exercise CapacityExercise Capacity
• Skeletal Muscle FunctionSkeletal Muscle Function• Muscle sizeMuscle size• Muscle strengthMuscle strength
• Body CompositionBody Composition
Preliminary 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
Forthcoming StudiesForthcoming Studies
Pre-Clinical InvestigationsPre-Clinical Investigations
• Determine the effects of exercise training on Determine the effects of exercise training on antitumor efficacy of doxorubicin (DOX) in MDA-antitumor efficacy of doxorubicin (DOX) in MDA-MB-231 breast cancer xenograftsMB-231 breast cancer xenografts
• Funded by US Dept of Defense BCRP - Concept Funded by US Dept of Defense BCRP - Concept AwardAward
Exercise/Chemotherapy InteractionExercise/Chemotherapy Interaction
PurposePurposeJones LW, Eves ND, Courneya KS, Baracos VE, Hanson J, & Mackey JR
MethodAthymic FemaleAthymic Female
HSD 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 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
Results
0
10
20
30
40
50
60
70
80
90
100
6 12 18 24 30 36 42 48 54
% S
urvi
ving
Days
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=25Ex + CTEx + CT N=21N=21 Events=16Events=16 Median Growth Delay=36 (>C0 p=0.029; Ex Only p=0.080) Median Growth Delay=36 (>C0 p=0.029; Ex Only p=0.080)CT Only CT Only N=21N=21 Events=13Events=13 Median Growth Delay=42 (>C0 p=0.0084; Ex Only p=0.029) Median Growth Delay=42 (>C0 p=0.0084; Ex Only p=0.029)
Log Rank P=0.015Log Rank P=0.015
35%35%
20%20%16%16%
Discussion
• Moderate intensity TM running does not significantly Moderate intensity TM running does not significantly influence DOX-induced tumor growth delay in MDA-influence DOX-induced tumor growth delay in MDA-MB-231 xenograftsMB-231 xenografts
• Trend for longer survival in DOX only suggests that Trend for longer survival in DOX only suggests that TM running may partially inhibit the efficacy of DOX TM running may partially inhibit the efficacy of DOX therapytherapy
• Clinical trial underway (DOD funded study)Clinical trial underway (DOD funded study)
Summary
Growing interest in role of exercise for cancer Growing interest in role of exercise for cancer survivorssurvivors
Preliminary evidence – safe, feasible, & Preliminary evidence – safe, feasible, & beneficial supportive interventionbeneficial supportive intervention
Current/forthcoming research addressing Current/forthcoming research addressing fundamental questionsfundamental questions
Integral part of comprehensive cancer careIntegral part of comprehensive cancer care