1. Targeting Taxane-Induced NeuropathyWith Exercise Constance Visovsky PhD, RN, APRN-NP Associate Dean of Student Affairs & Director Community Engagement Jim Bovaird, PhD Statistician University of Nebraska-Omaha

2. Background The use of taxanes in breast cancer chemotherapy regimens is considered standard first line therapy. 50%-60% of all patients who receive taxanes will develop chemotherapy-induced peripheral neuropathy (CIPN). Clinical manifestations include pain; numbness, tingling, diminished proprioception, and decreased vibration and touch sensation. CIPN remains a significant toxicity and no evidence-based preventative or treatment strategies are available The sensory and motor neuron dysfunction accompanying taxane chemotherapy interferes with physical functioning, impairs quality of life and can be disabling.

3. Purpose To use a 2-group RCT to pilot test a 16-week home- based combination aerobic/resistance exercise program for reducing symptoms of chemotherapy-induced peripheral neuropathy in a convenience sample of 19 women receiving taxane-based chemotherapy for breast cancer.

4. Physiological Framework Taxanes induce sensory and motor neuropathy by impairing axon structure and function. Loss of peripheral nerve vasculature and mitochondrial dysfunction follow. Results in neuropathic pain and functional impairment.

5. Study Design Two group, randomized clinical trial 19 women with Stage I-IIIa breast cancer receiving taxane-based chemotherapy were randomly assigned to either an aerobic and resistance training exercise program or an attention control group.

6. Attention Control Group Detailed Guide: Breast Cancer What Happens After Treatment for Breast Cancer? Completing Treatment can be both stressful and exciting. You will be relieved to finish treatment, yet it is hard not to worry about cancer coming back. (When cancer returns, it is called recurrence.) This is a very common concern among those who have had cancer. For ore information on this please refer to the separate American Cancer Society document, Living With Uncertainty: The Fear of Cancer Recurrence. It may take a while before your confidence in your own recovery begins to feel real and your fears are somewhat relieved. Even with no recurrences, people who have had cancer learn to live with uncertainty. It is important to keep medical insurance. Even though no one wants to think of their cancer coming back, it is always a possibility. If it happens, the last thing you want is to have to worry about paying for treatment. Should your cancer come back the American Cancer Society document, When Your Cancer Comes Back: Cancer Recurrences gives you information on how to manage and cope with this phase of your treatment. You can get this document by calling 1-800-ACS-2345. HOPE Study Daily Planner

7. Features of the Intervention Pedometer, exercise bands: Exercise Guide : DVD using peer models demonstrating the performance of the exercises Exercise Diary : record of the type of exercise band used, the number sets and repetitions done, steps/distance and the number of exercise sessions per week

8. Exercise Intervention Aerobic Exercise: Walking 30 min daily Strength Training Exercises: – Arm Flexion – Arm Extension – Hip Flexion – Hip Extension – Leg Extension – Ankle Plantar and Dorsiflexion

9. Exercise Diary

10. Date: Sunday Monday Tuesday Example: Bicep Curls 5lb/12reps/2sets Warm-up/ Cool Down Bicep Curls Y / G / R / B Reps/ Sets Y / G / R / B Reps/ Sets Y / G / R / B Reps/ Sets Triceps Press Y / G / R / B Reps / Sets Y / G / R / B Reps / Sets Y / G / R / B Reps / Sets Straight Leg Raises Y / G / R / B Reps / Sets Y / G / R / B Reps / Sets Y / G / R / B Reps / Sets Leg Extension Y / G / R / B Reps / Sets Y / G / R / B Reps / Sets Y / G / R / B Reps / Sets Knee Extension Y / G / R / B Reps / Sets Y / G / R / B Reps / Sets Y / G / R / B Reps / Sets Ankle Plantarflexion Y / G / R / B Reps / Sets Y / G / R / B Reps / Sets Y / G / R / B Reps / Sets Exertion Level (0-10) Example: Walking Mile/ Steps/ Time 0.25miles/ 1200steps/ 8 minutes Mile/ Steps/Time Walking Mile/ Steps/ Time Mile/Steps/ Time Mile/Steps/ Time Exertion Level (0-10)

11. Sample Characteristics (n =19) Age 48.8 (range 24-65) Race Caucasian 16 (84.2%) African American 2(11%) Asian 1 (5.3%) Employed 15 (78.9%) Other Illnesses 8 (42.3%) Married or Partnered 13 (68.4%) Surgery Type Neoadjuvant 5 (26.3%) Lumpectomy 8 (42.1%) Mastectomy 6 (31.6%) Disease Stage Stage I9 (47.4%) Stage II7 (36.8%) Stage III2 (10.5%)

12. Data Collection Data collection: baseline, 4, 8, 12, 16 and 24 weeks (2 months post-intervention) Instruments Neuropathy symptoms & QOL: (FACT- Taxane) Likert scale: 0 (not at all) - 4 (very much) Gait & Balance (Timed Get Up and Go) Muscle strength (Dynamometry)

14. Data Analysis A general linear mixed (GLM) modeling was utilized to: evaluate the effect of the intervention (aerobic and resistance exercises) on change in outcomes at post intervention (16 weeks) at follow-up (24 weeks after the start of taxane chemotherapy).

15. Results: Neuropathy Symptoms

16. Results: Quality of Life

17. Results: Gait & Balance

18. Results: Muscle Strength

19. Conclusions CIPN remains a significant dose-limiting toxicity of many chemotherapy regimens. No gold-standard for the prevention or treatment of CIPN exists.

20. Conclusions Combination of aerobic and resistive exercise was feasible and effective in reducing neuropathic symptoms, improving gait & balance, specified areas of muscle strength, and QOL related to CIPN in women with breast cancer. Exercise is a promising intervention that can be easily applied to ambulatory cancer patients under treatment.

21. Thank You!