Peripheral Neuropathy (PN): Late Effects of Cancer Therapy

1. Peripheral Neuropathy (PN):Late Effects of Cancer Therapy

2. Objectives The learner will be able to: • Examine the pathophysiology of PN. • Describe assessment practices to characterize clinical manifestations of PN. • Discuss pharmacologic and non-pharmacologic treatment strategies and implications for nursing care.

3. The Problem • Incidence: Ranges from 10%-100% of cancer survivors • Definition: Peripheral sensory, motor, autonomic nerve damage • Consequences: Persistent pain, decreased function and quality of life • Dose-limiting • Treatment: Few options for prevention and management

4. Transduction Transmission Modulation Perception Interpretation Behavior Physiology of Pain Perception Injury Brain Descending Pathway Dorsal RootGanglion PeripheralNerve AscendingPathways C-Fiber A-beta Fiber Dorsal Horn A-delta Fiber Spinal Cord

5. Sensory and Motor Fibers

6. Pathophysiology • Caused by five major drug classes • Taxanes • Platinums • Vinca alkaloids • Protease inhibitors • Anti-angiogenesis agents

7. Known or Hypothesized Etiologies • Damage to neuronal cell bodies in the dorsal root ganglion • Axonal toxicity (demyelination, impaired transport) • Axonal membrane ion channel dysfunction (Na+ channel) • Mitochondrial damage and inflammation • Vascular changes • Protein C kinase epsilon isoform (PKCε) • Cytokine-mediated inflammation • Nerve growth factor deficiency

8. Factors Contributing to Chemotherapy-Induced Neuropathy • Drug dependent • Regimen dependent • Dose intensity • Cumulative dose • Patient characteristics (age, physical status) • Comorbid conditions (diabetes, alcoholism) Visovsky, C. (2003). Cancer Investigation, 21(3), 439-51. Dropcho, E.J. (2004). Seminars in Neurology, 24(4), 419-26.

9. Clinical Manifestations • Length dependent - nerves “die-back” from the tips • Stocking/glove distribution • Sensory symptoms • Numbness • Paresthesias • Cold hyperalgesia • Pain • Motor symptoms • Autonomic symptoms

10. Possible Descriptions of Neuropathic Pain • Sensations • Numbness • Tingling • Hot burning • Lancinating • Electric-like • Raw skin • Shooting • Deep, dull, bone-like ache • Signs/Symptoms • Muscle and tissue spasm, tightness, and tenderness • Muscle weakness and atrophy • Skin color changes, rashes, swelling, and temperature abnormality 1. Galer, B.S. (195). Neurology,45(suppl 9), S17-S25. 2. Backonja, M.M., & Galer, B.S. (1998). Neurology Clinics, 16, 775-789.

11. Cutaneous Hypersensitivity and Abnormal Sensations • Petersen KL, et al. Pain. 2000;88:125-133.

12. Measurement Approaches The Neurologist “Gold Standard” • A comprehensive approach improves validity. • Subjective sensory, motor, autonomic symptoms • Objective neurologic examination

13. Drugs and Fibers

14. Two Cases Patient 1 • Received paclitaxel for breast cancer • Low cum. dose completed > 1 year ago • Diabetic • Numbness, tingling, and NP to knees and in upper extremities • Impaired balance • Pain with walking and turning on the faucets • Diminished pin and vibration sensation to knees • Normal strength • All reflexes absent Patient 2 • Received oxaliplatinfor colon cancer • Moderate cum. dose still ongoing • No known risk factors • Numbness and tingling to arches • Pain when walking • Normal pin and diminished vibration sensation in toes • Normal strength • Reduced achilles reflex

15. Gabapentin as Treatment • FDA approved for postherpetic neuralgia • Anticonvulsant - uncertain mechanism • Limited intestinal absorption • Usually well tolerated; serious adverse effects rare • Dizziness and sedation can occur. • No significant drug interactions • Peak time: 2 to 3 h; elimination half-life: 5 to 7 h • Usual dosage range for neuropathic pain up to 3,600 mg/d (tid–qid)* *Not approved by FDA for this use.

16. Tricyclic Antidepressants as Treatment • Commonly reported AEs (generally anticholinergic): • Blurred vision • Cognitive changes • Constipation • Dry mouth • Orthostatic hypotension • Sedation • Sexual dysfunction • Tachycardia • Urinary retention • Desipramine • Nortriptyline • Imipramine • Doxepin • Amitriptyline FewestAEs Most AEs AEs = adverse effects.

17. Other Potential Treatments Intravenous Calcium and Magnesium • Theory: Increasing calcium concentrations leads to Na channel closing and subsequent decreased oxaliplatin-induced hyper-excitability of peripheral neurons. Vitamin E • Mixed results regarding interference with chemotherapy efficacy due to antioxidant effects

18. Non-Pharmacologic Treatment • Interruption of therapy strategies if neurotoxicity readily reversible • Acupuncture – limited data • No data in PN on: • Physical activity/exercise • TENS (transcutaneous external nerve stimulation) • Meditation/bio-feedback

19. Safety Measures • Always wear shoes both indoors and outside. • Use knives, scissors, box cutters, and other sharp objects with care. • Protect hands by wearing gloves when cleaning, working outdoors, or doing repairs. • Make sure the house is well lit. • Keep a night light on in bedrooms and along the path to the bathroom. • Cover steps and bathtub/shower with a non-skid surface. • Clear stairs and hall of objects.

20. Safety Measures • Mark the edge of the step with a bright color to help determine where the step ends. • Use handrails. • Tape down the edges of all throw rugs to avoid tripping. • Test the temperature of the water with an area of the body that is not affected by neuropathy before any bathing and dish washing. • Always check feet and shoes at the beginning and end of each day. Small pebbles or poorly fitted shoes can irritate your foot and cause an open sore. Look for any redness or blisters that may not be able to be felt.

21. Nursing Care • Teach patients to: • Report symptoms. • Focus on safety. • Take time to assess PN using objective and subjective approaches. • Collaborate with colleagues regarding the need for chemotherapy dose modifications. • Monitor efficacy of interventions.