Peripheral Neuropathy

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Peripheral Neuropathy

• Evelyn Robles-Rodriguez
• RN, MSN, APN
• Cooper University Hospital

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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

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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

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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

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What about cancer treatment?

• Damage to nerves can occur with
• Surgery
• Radiation therapy
• Chemotherapy

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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

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Radiation Therapy

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

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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)

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Chemotherapy likely to cause peripheral neuropathy

• 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)

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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

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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

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Less common symptoms

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

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How common is CIPN?

• 3-7 in those treated with single agents
• 38 in those treated with multiple agents

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When do symptoms start?

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

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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

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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

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What can you do to treat peripheral neuropathy?
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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

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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

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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

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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

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What treatments are available?
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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

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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

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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

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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

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Anticonvulsants

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

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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

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Glutathione

• Thiol tripeptide may hamper platinum accumulation
  in nerves
• Three studies to date
• 1st 1500 mg/m2 IV, no grade 3-4 toxicity
• 2nd 3 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

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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

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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

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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

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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

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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

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Non-pharmacology Interventions Studied

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

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Other Things to Consider

• Relaxation therapy
• Guided imagery
• Distraction
• Biofeedback

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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

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Emotional support

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

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Help is available!

• Dont suffer in silence