Peripheral Neuropathy

Peripheral Neuropathy Evelyn Robles-Rodriguez RN, MSN, APN Cooper University Hospital

What is peripheral neuropathy (PN)? • Irritation or damage to nerves outside the brain and spinal cord • Causes difficulty in communication between nerves or group of nerves

What are peripheral 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

What can cause PN? • 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

What about cancer treatment? • Damage to nerves can occur with: • Surgery • Radiation therapy • Chemotherapy

Surgery • 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

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

Chemotherapy • 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”)

Chemotherapy likely to cause peripheral neuropathy • Platinums(cisplatin, carboplatin, oxaliplatin) • Taxanes (Taxolor paclitaxel, Taxotere or docetaxel) • Epothilones (Ixabepilone or Ixempra) • Plan alkaloids (vinblastine, vincristine, vinorelbine, etoposide) • Thalidomide and lenalidomide (Revlimid) • Bortezomib (Velcade)

Symptoms of Chemotherapy Induced Peripheral Neuropathy (CIPN) • 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

More symptoms of CIPN • 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

Less common symptoms • Difficulty swallowing • Urinary incontinence • Constipation • Impotence • Dizziness with standing

How common is CIPN? • 3-7% in those treated with single agents • 38% in those treated with multiple agents

When do symptoms start? • Can begin anytime after treatment starts • Sometimes occurs at end of treatment • Can worsen as treatments go on

How long do symptoms last? • 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

What affects PN longevity? • 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

What can you do to treat peripheral neuropathy?

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

What may your doctor do? • 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

What can you do to stay safe if affected by PN? • 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

What else can you do? • 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

What treatments are available?

Prevention of and treatment for CIPN? • 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

Vitamin E • 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

Calcium and Magnesium • 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

Chemoprotectants • 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

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

Glutamine • 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

Glutathione • Thiol tripeptide may hamper platinum accumulation in nerves • Three studies to date • 1st 1500 mg/m2 IV, no grade 3-4 toxicity • 2nd3 g/m2, 58% vs. 39% able to receive all cycles of chemo and improved QOL • 3rd 1.5 g/m2 17 vs. 88% had clinical evidence of PN • Need further randomized trials

Alpha lipoic acid • 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

Acetyl L-carnitine • 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

Tricyclic antidepressants • 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

Treatment for nerve pain • 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

Which approved? • 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

Non-pharmacology Interventions Studied • Acupuncture • Assistive devices • Physical activity and exercise • Pulsed infrared light therapy • Transcutaneous nerve stimulation • Spinal cord stimulation

Other Things to Consider • Relaxation therapy • Guided imagery • Distraction • Biofeedback

Other approaches • 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

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

Help is available! • Don’t suffer in silence

Peripheral Neuropathy