 Irritation or damage to nerves outside the brain and spinal cord  Causes difficulty in communication between nerves or group of nerves

 Long, wire-like fibers  Transmit nerve impulses and sensory information from the body to the spinal cord  Carry motor signals for muscle movement and other functions from the brain and spinal cord to rest of body and organs

 Chronic diabetes and uremia  Infection which affects nerves such as shingles (post herpetic neuralgia)  Excess alcohol  Tumor pressing on a nerve  Spinal cord injury  Low vitamin B levels (especially B12)  Poor circulation

 Damage to nerves can occur with: › Surgery › Radiation therapy › Chemotherapy

 Can cause damage to nerves near the surgical site  Side effects reported with damage: › Burning › Shooting pain › Electric tingling › Numbness in skin around surgical site

 More common in 1960s with older treatments  Much less common today but still can occur  Side effects can include: › Weakness › Pain

 Polyneuropathy most common form of neuropathy (affects several nerves)  Usually affects both sides of the body equally  Symptoms usually begin in feet and can progress to hands (referred as “stocking/glove distribution”)

 Platinums (cisplatin, carboplatin, oxaliplatin)  Taxanes (Taxol or paclitaxel, Taxotere or docetaxel)  Epothilones (Ixabepilone or Ixempra)  Plan alkaloids (vinblastine, vincristine, vinorelbine, etoposide)  Thalidomide and lenalidomide (Revlimid)  Bortezomib (Velcade)

 Pain (can be constant or come and go, shooting, electric or stabbing)  Burning  Tingling (“pins and needles”)  Numbness (decreased sensation of pressure, touch, temperature)  Increased sensitivity to temperature (especially cold), touch or pressure

 Difficulty using fingers to pick up, hold or handle things such as buttons, writing  Problems with balance  Tripping or stumbling with walking  Shrinking or weak muscles  Loss of or reduced reflexes

 Difficulty swallowing  Urinary incontinence  Constipation  Impotence  Dizziness with standing

 3-7% in those treated with single agents  38% in those treated with multiple agents

 Can begin anytime after treatment starts  Sometimes occurs at end of treatment  Can worsen as treatments go on

 Can be short term › Last a few days › Stop after treatment ends  Can be long term › Persist between treatments › Continue 6-24 months after treatment ends  Can become a permanent problem

 Age  Genetic predisposition  Chronic conditions (diabetes, kidney failure, HIV)  Amount of each dose of chemo  Total dose of chemo  Drug combination  Previous chemo  Previous problems with PN

 Talk to your doctor or nurse immediately after symptoms begin  Do not delay telling  Failure to disclose symptoms can lead to life-altering problems

 Reduce dose of chemo (this is safe and still give you the same benefit as higher doses)  Give smaller doses 2-3X vs. 1X per week  Give dose over longer period of time  Give longer breaks between chemo  Alter chemo cycle

 Wear gloves and warm socks especially in the cold  Wear shoes inside and outside your home  Protect your hands when working  Keep your house well lit/keep night light  Use nonskid surface in shower/tub  Clear floor of objects and watch for rugs  Test temperature of water with non- affected body part  Check your feet at end of each day

 Avoid alcohol  If diabetic, control your blood sugar  Treat your pain as prescribed  Pay attention to your shoes  Sit down as much as possible if feet are a problem

 Several preventions and treatments have been tried with mixed results  There is no sure way to prevent CIPN to date  Mixed results with treatments  Research needs to continue

 Antioxidant  May protect nerves from damage due to cytotoxic drugs  3 studies examined effect giving 300 to 600 mg during and 3 mths after treatment ended  Evidence of less nerve damage in group who took Vitamin E  Other study found deficient Vitamin E levels in pts receiving cisplatin who had PN

 Tested in pts who received oxaliplatin which binds to calcium and magnesium  Given 1g of calcium and magnesium before and after infusion  65% of those treated vs. 37% of non- treated had no PN symptoms  Retrospective, nonrandomized study

 Amifostine which detoxifies chemotherapy drugs and facilitates DNA repair  Three studies examined effect on PN  No differences in sensory or motor symptoms found in pts treated with amifostine

 Carbamezapine (Tegretol) with oxaliplatin  No neuropathy in treated group vs. 30% in historical control group  Need placebo controlled trial

 Nonessential amino acid  Thought to have neuroprotective effects for paclitaxel  8% of those treated vs. 40% not reported PN symptoms in one study (10g daily)  Other study (10 g 3X/d) in those treated noted less symptoms  Larger, randomized, placebo studies needed

 Thiol tripeptide may hamper platinum accumulation in nerves  Three studies to date  1 st 1500 mg/m2 IV, no grade 3-4 toxicity  2 nd 3 g/m2, 58% vs. 39% able to receive all cycles of chemo and improved QOL  3 rd 1.5 g/m2 17 vs. 88% had clinical evidence of PN  Need further randomized trials

 Fatty acid which converts sugar into energy and is also an antioxidant  Some studies with diabetics  4 randomized, double-blind, placebo controlled studies  600 mg/d IV  Clinically significant improvements in pain, burning and numbness after 5 wks  Need studies for CIPN

 Nutritional supplement which functions as an antioxidant  2 studies in pre-existing CIPN  1 g/d IV or 1 g/tid orally  Studies limited by small sample size and not randomized

 Nortriptyline – blocks reuptake of serotonin and norepinephrine in pain modulating system of CNS  Analgesic effect  Escalating dose of up to100 mg/d  Modest benefit in study of cisplatin induced PN

 Antidepressants (amitriptyline, nortriptyline, and desipramine)  Anticonvulsants (gabapentin or Neurontin, pregabalin or Lyrica)  Steroids (short term use only)  Local anesthetics (capsaicin, EMLA, lidocaine 5%)  Opioids and methadone

 Only ones approved by FDA for treatment of neuropathic pain › Duloxetine (cymbalta) – diabetic PN › Pregabalin (lyrica) – diabetic PN and post herpetic neuralgia › Lidocaine patches 5% - post herpetic › Gabapentin (neurontin) – post herpetic

 Acupuncture  Assistive devices  Physical activity and exercise  Pulsed infrared light therapy  Transcutaneous nerve stimulation  Spinal cord stimulation

 Relaxation therapy  Guided imagery  Distraction  Biofeedback

 PT - can help improve balance, strength and safety  OT – can help improve fine motor coordination such as writing and help adapt your home and work environment  Pain specialists – can educate you about treatment options and help manage your symptoms  Podiatrist – can help you find the right shoes for your symptoms

 Talk to your oncology team  Consider support groups  Visit respected internet websites › cancer.gov › cancer.org › neuropathy.org › cancercare.org › lbbc.org

 Don’t suffer in silence