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Physical-Based Therapeutic Approaches for Cancer-Related Pain

Physical-Based Therapeutic Approaches for Cancer-Related Pain. Lee W. Jones, Ph.D. Department of Surgery Duke University Medical Center 2 nd Annual Pain Management Symposium June 6 th , 2008. Presentation Outline. Brief Overview of Cancer-Related Pain (CRP) Management of CRP

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Physical-Based Therapeutic Approaches for Cancer-Related Pain

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  1. Physical-Based Therapeutic Approaches for Cancer-Related Pain Lee W. Jones, Ph.D Department of Surgery Duke University Medical Center 2nd Annual Pain Management Symposium June 6th, 2008

  2. Presentation Outline • Brief Overview of Cancer-Related Pain (CRP) • Management of CRP • Role of Physical-Based Approaches for CRP • Future Directions

  3. Brief Overview of CRP

  4. Overview of CRP • 30% to 50% undergoing therapy • 70% to 90% advanced disease • Bone pain most common (>75% related to neoplastic invasion) • CRP Syndromes • Nociception - damage to pain receptors • Neuropathic - nerve damage (peripheral neuropathy) • Treatment-related pain – damage to receptors by Sx, RT, CT, & ET

  5. The Symptom Cluster PAIN FATIGUE  QOL DISTRESS FUNCTION DECLINE

  6. Management of CRP

  7. Management of CRP • Pharmacologic Approaches • Opoids / Analgesics / NSAIDs • Bisphosphonates / new approaches • Inadequate pain relief • Not benign (GI toxicity / cog dysfunction) • Non-Pharmacologic Approaches • Surgery / psychological (grp psychotherapy / stress management, etc.) • Address physical dimensions??

  8. Role of Physical-Based Approaches for CRP

  9. Types of Physical-Based Approaches • Yoga • mediation, gentle postures, breathing exercises • Tai Chi • Meditative form of exercise & postures • Structured Exercise Training • Bodily activity aim of improving fitness & health • Physical / Rehabilitation Therapy • Prevention, management, & tx of movement disorders

  10. Review ofLiterature • >50% of exercise studies conducted in early-stage breast cancer patients • >50% completed during treatment • Majority tested aerobic-based interventions • Cycle ergometry/treadmill walking • 3d.wk for 6-24 weeks, moderate intensity • Adherence levels (if reported) > 70% Jones & Demark-Wahnefried. Lancet Oncol 2007

  11. 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

  12. Prior Work • Examined potential role of exercise in the following: Descriptive Intervention Early-Stage Breast Cancer Metastatic Breast Non-Hodgkins Lymphoma Inoperable NSCLC Multiple Myeloma Preoperative NSCLC Primary Brain Cancer Neoadjuvant Breast Endometrial Adjuvant NSCLC Colorectal Anemic Cancer Pts Prostate NHL

  13. Prior Clinical Trials

  14. REHAB Trial • Examined the effects of endurance training on exercise capacity, QOL, & biologic outcomes in PM breast cancer survivors Aims • Effects on QOL (FACT-B) and exercise capacity (VO2peak) • Effects on metabolic hormones (insulin, IGF-1, IGFBPs), & CV risk factors (BP, CRP, etc.) Courneya, Jones et al. JCO 2003

  15. REHAB TrialMethod Patients 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. JCO 2003

  16. REHAB TrialPatient Characteristics Courneya, Jones et al. JCO 2003

  17. REHAB TrialResults – Exercise Capacity - ITT 2.7 mL.kg.min within group ( 17.4%) (p<.001) 3.4 mL.kg.min between groups Courneya, Jones et al. JCO 2003

  18. REHAB TrialResults – QOL +9.1 points within group (clinically meaningful) (p<.001) +8.8 between groups Courneya, Jones et al. JCO 2003

  19. REHAB TrialResults – Fatigue EG  fatigue (adjusted analyses) -9.3 points within group (clinically meaningful) (p<.006) -7.3 between groups Courneya, Jones et al. JCO 2003

  20. REHAB TrialOther Results 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)

  21. EXTRA Trial • Determine if a 12-week endurance exercise training program can improve QOL in anemic pts receiving Aranesp Aims • Effects on QOL (FACT-An), fatigue, exercise capacity (VO2peak) • Effects on Hb response & dosing requirement Sponsored by Amgen Inc,

  22. EXTRA TrialMethod Patients 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

  23. EXTRA TrialParticipant Characteristics

  24. EXTRA TrialResults – Exercise Capacity - ITT 3.5 mL.kg.min within group ( 22%) (p<.001) 3.0 mL.kg.min between groups Courneya, Jones et al. JCO Submitted

  25. EXTRA TrialResults – QOL +13.4 points within group (clinically meaningful) (p=.637) -6.9 between groups Courneya, Jones et al. JCO Submitted

  26. EXTRA TrialResults – Hb Outcomes

  27. 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

  28. Pre-Op StudyMethods Patients and Eligibility • Suspected stage I-IIIa NSCLC with or without preoperative histologic confirmation • Surgery for curative intent • No contraindications to CPET Jones et al. Cancer 2007

  29. Pre-OpPatient Flow Number of Patients Screened N=43 Reasons for Non-Eligibility (n=8) Geographical Location (n=6) Number of Patients Eligible N=35 (35/43 = 81%) Reasons for Non-Consent (n=10) Not Interested (n=6) Baseline Tests Completed N=25 (25/35 = 71%) Patients Becoming Ineligible N=5 (5/25 = 20%) Reasons for Non-Eligibility (n=5) Became inoperable (n=4) Pre-Surgery Tests Completed N=18 (18/20 = 90%) Reasons for Drop Out (n=2) No transportation (n=1) Work Commitments (n=1) Reasons for Drop Out (n=5) Died (n=2) Sx complications Post-Surgery Tests Completed N=13 (13/18 = 72%) Jones et al. Cancer 2007

  30. Pre-Op StudyParticipant Characteristics (n=20) Jones et al. Cancer 2007

  31. Pre-Op StudyResults – VO2peak -ITT 2.4mL.kg.min ( 15%) (p=.002) Jones et al. Cancer 2007

  32. Pre-Op StudyResults – VO2peak (adherence) ≥80% adherence: 3.3mL.kg.min ( 20%) (p=.006) <80% adherence: 0.8mL.kg.min ( 5%) (p=.129) Jones et al. Cancer 2007

  33. Pre-Op StudyResults – VO2peak (n=13)  18%  18% ~0% Jones et al. Cancer 2007

  34. Current Clinical Trials

  35. Duke Infrastructure Exercise Training Exercise Testing

  36. NSCLC Post-Op Study Jones LW, Crawford J, Garst J, Kraus WE, Peterson B • Determine the feasibility of exercise training among 20 postsurgical NSCLC patients 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 Funded by the Lance Armstrong Foundation

  37. 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

  38. Breast Neoadjuvant Study Jones LW, Marcom PK, Dewhirst, M, Blackwell K, Allen J, Douglas PD, Kraus WE, Peterson, B • Effects of exercise training on tumor response to chemotherapy among 20 breast cancer patients undergoing neoadjuvant chemotherapy Aims • Effects of exercise on exercise capacity • Examine effects of exercise on tumor physiology, tx response, QoL, cardiac function, & blood markers • Cycle ergometry (3x/wk, 30-45mins, 60-100% VO2peak for 12 weeks) • 6 patients completed; 4 on study Sponsored by US DOD Breast Cancer Research Program

  39. Glioma Profiling Study Jones LW, Reardon D, Friedman HS, Friedman A, Major N, Kraus WE, Peterson B • To prospectively assess changes in exercise capacity and skeletal muscle function across primary brain tumor therapy (n=25 HGG; n=10 LG) • Baseline (pre chemo/XRT; 6 weeks; 6 months) Aims • Examine feasibility of exercise capacity & skeletal muscle function assessments • Assess changes in these outcomes & QOL • Disease progression & overall survival Funded by NCI – R03

  40. Assessments • Exercise Capacity • Skeletal Muscle Function • Muscle size • Muscle strength • Body Composition

  41. 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

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