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Peripheral Neuropathy: Will it ever go away? Problems, Causes, Solutions

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Cindy Tofthagen, PhD, ARNP, AOCNP, FAANPUniversity of South Florida

College of Nursing

Chemotherapy Related Neuropathy: Managing this Nerve Wracking ProblemCindy Tofthagen, PhD, ARNP, AOCNP, FAANPUniversity of South FloridaCollege of Nursing

Topics of Discussion

• What is chemotherapy induced peripheral neuropathy (CIPN)?

• What are the risk factors?

• What can we do about it?

What is CIPN?

A group of neuromuscular symptoms that result from nerve damage caused by drug therapies used in the treatment of cancer.

Affects 30-100% of patients getting specific neurotoxic chemotherapy drugs.

The most commonly used classes of drugs causing peripheral neuropathy are taxanes (Taxol and Taxotere) and platinum based drugs (cisplatin and oxaliplatin).

(Ocean & Vahdat, 2004; Visovsky, 2003)

•Sensory, motor, or autonomic

•Vary from person to person based on type of treatment and individual differences

•Numbness, tingling, and discomfort in the upper or lower extremities are the hallmarks of peripheral neuropathy

Symptoms

Problem

CIPN can last for months to years after chemotherapy and sometimes is permanent.

It can interfere with the ability to perform usual activities.

Risk Factors• Increasing dose• Pretreatment or concurrent treatment with other

neurotoxic chemotherapies• Diabetes• Hypothyroidism• HIV infection• Charcot-Marie-Tooth disease• Autoimmune disorders• Vitamin B12 deficiency• Chronic alcohol abuse• Shingles

Sue’s Story

Supposedly chemotherapy increased my chances of living 5years by 8%. I don’t want to live for another 5 years like this.My hands and fingers are numb. My feet are numb. My legs arenumb from my knees to the bottom of my feet. I have pain,gnawing, burning, and cramping most of the time. My legsache and feel stiff and heavy all the time. Driving is a problem,walking is a problem, Being on my feet is a problem. My handsdon’t work. I feel collapsed, dizzy, and weak all day, everyday, all the time. I have disabling fatigue. I feel like I have beenpoisoned.-written in 2008 by Sue, colorectal cancer survivor.

(Tofthagen, 2010)

FunctionalDisability

Loss of Sensation

Peripheral Neuropathy

Exaggerated Sensation

Walking

Driving

Hobbies

Picking up

things

Relation-

ships

Chores

WorkWritingExercise

Sleep

Sexual

Activity

4 Approaches to CIPN

1) Prevent it

2) Recognize it early

3) Control the pain

4) Minimize effects on quality of life

Prevent it

A variety of preventative strategies have been evaluated thus far with varying degrees of success, including:

Calcium/Magnesium InfusionsAlpha-lipoic acidB VitaminsGlutamine/glutathioneVitamin E

Calcium/Magnesium Infusions • Numerous clinical trials supporting its use

• One trial was closed because of safety concerns

• Recent meta-analysis confirmed safety and efficacy of Calcium and Magnesium infusions for prevention of neuropathy caused by oxaliplatin only

• Reduces the incidence of grade 2 but not grade 1 neuropathy

(Grothey et al., 2011; Hochster, Grothey, & Childs, 2007; Ishibashi, Okada, Miyazaki, Sano, & Ishida, 2010; Wen et al., 2012)

Genetics• Neurotoxicity may be directly related to

individual variations in neurotoxic drug metabolism, distribution, and elimination.

• Genetic polymorphisms associated with CIPN may lead to genetic tests to help identify individuals likely to develop severe neuropathy

Bergmann, et al., 2011; Sissung, et al., 2006; Renbarger, et. al., 2008; Hertz, et al., 2012; Kroetz, et al., 2010; Schneider, et al., 2011.

Recognize it Early

• Early recognition is key because dose adjustments may be required that may lesson severity and minimize long-term nerve damage.

What to tell your healthcare team

1. What symptoms are you having?

2. Are the symptoms on one or both sides?

3. How much of the extremity is involved?

4. How severe and distressing is each symptom?

5. Are symptoms constant or do they come and go?

6. How are your activities and lifestyle being affected?

Controlling the Pain

Controlling Neuropathic Pain

Neuropathic pain is severe, difficult to treat, and may not respond well to narcotic analgesics.

Image retrieved from http://www.topnews.in/health/files/chronic-pain.jpg

Describing Your Pain•Onset •Location •Duration •Characteristics •Aggravating Factors •Relieving Factors •Treatments tried

Duloxetine

•Based on primary results (n=220) Duloxetine 60mg daily:•Diminishes CIPN pain in the majority• Improves function & QOL•One of the few drugs recommended that has data to support its use for painful CIPN

Treatment of Neuropathic Pain

First LineTricyclic Antidepressants Gapapentin or Pregabalin

Second LineSerotonin-norepinephrine reuptake inhibitors Lidocaine Patch

Third LineTramadol or Controlled Release Opioid

Fourth LineCannabinoids, methadone, lamotrigine, topiramate,

valproic acid

Moulin, et al., 2007

Drug /Class Starting Dose Titration Maximum Dose

Trial Duration

Nortriptyline/TCA

25mg at bedtime

Increase by 25mg every 3-7 days as tol

150mg/day 6-8 weeks

Desipramine/TCA

25mg at bedtime

Increase by 25mg every 3-7 days as tol

150mg/day 6-8 weeks

Duloxetine/SSNRI

30mg/day Increase to 60mg/day in 7 days

60mg /BID 4 weeks

Venlafaxine/SSNRI

37.7mg once or twice a day

Increase by 75 mg/week

225mg/day 4-6 weeks

Gabapentin 100-300mg TID 100-300mg TID every 1-7 days as tolerated

3600 mg/d (1200 mg 3 times daily)

3-8 wk forTitration and 2 weeks at max dose

Pregabalin 50mg TID or 75mg BID

Increase to 300mg/day after 3-7 days, then by 150mg/d every 3-7 days

600mg/d 4 weeks

Dworkin, et al., 2010

Minimizing Neuropathy’s Effects on Quality of Life

Cycle Number Perceived Loss of Balance

Fall Risk

FALL PREDICTORS

Treatment of Foot NeuropathyPatients with numbness in the feet should:

• wear comfortable, properly fitting shoes• avoid sandals, open toed or open heeled shoes• inspect feet daily for injury • avoid walking barefoot or in socks alone• always check for foreign objects in shoes before putting them on• change shoes in the middle of the day to avoid continued pressure in the

same locations

(Plummer & Albert, 2008).

Home Safety

• Water temperature for bathing should be carefully assesses and the thermostat on the water heater should be adjusted to a maximum of 100 degrees Fahrenheit

• Run cold water first

• Use protective gloves when washing dishes

• Always use pot holders (Armstrong, Almadrones, & Gilbert, 2005; Hot Water Burns Like Fire Campaign, 2006).

Home Safety

• Living areas should be kept well lit

• Keep walkways clear

• Nightlights should be kept on in hallways, bathrooms and bedrooms, nonskid mats in the shower or bathtub

(Armstrong, Almadrones, & Gilbert, 2005; Visovsky, Collins, Abbott,Aschenbrenner, & Hart, 2007).

Home Safety• Store frequently used items in easy-to-reach locations• Remove throw rugs and mats• Use sturdy chairs with arm rests• Use a long handled reacher to pick up items from the floor • Remove clutter around the house• Install hand rails in the tub and beside the toilet• Use a shower chair and a hand held shower• Use hand railing when climbing stairs,• Add a strip of brightly colored tape to the steps so that the outline

ofeach step is clearly visible,

• Keep walkways and stairs in good repair and free of clutter and debris

Self-Care Techniques• A study of self-reported self care techniques used by patients with

related neuropathy (n=450) indicate techniques that patients found helpful in relieving symptoms include:

• warm baths (66%)• walking (60%) • massage (41%) • rubbing cream on the feet (47%)• elevating feet (57%)• staying off the feet (59%)• acupuncture (12%) • meditation (20

(Nicholas et al., 2007)

Exercise• Compared to healthy people, persons with neuropathy

have reduced proprioception, lower extremity sensation, and reduced ankle strength predisposing them to falls

• Strength and balance training results in fewer falls

• Safe for people with peripheral neuropathy

• Tai Chi, a low impact form of Chinese martial art, may help reduce falls and improve balance

(Gillespie et al., 2009; Morrison, Colberg, Mariano, Parson, & Vinik, 2010; Allet, et al., 2010; Kruse et al., 2010).

Referrals• Neurologist to establish/confirm diagnosis

• Pain management

• Physiatrist-physician who specialize in cancer rehabilitation, locate one at http://www.cancer.net/survivorship/rehabilitation

• Physical therapist -specific exercises designed to help improve muscle strength and balance

• Occupational therapists -maintain your independence, adjust to physical limitations

• Support groups and mental health professionals

• Podiatrists –recommend footwear, and fit for orthotics(Tofthagen, 2012)

Community Resources

Summary

• Neuropathy is an uncomfortable and distressing symptom that can interfere with your ability to do the activities you want and need to do on a daily basis.

• Scientists are looking for ways to prevent neuropathy caused by chemotherapy.

• Patients can get better control of neuropathy symptoms and their effects on quality of life by being aware of treatment options, communicating with their healthcare team and seeking out resources within their community.

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