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Side EffectsPeripheral Neuropathy from Treatment

Last update: 10/30/2014

Introduction | Symptoms | Drugs that Cause | In the News
Tips to avoid secondary injuries |
Treating Neuropathy| ResourcesResearch News

NEW Clinical Trials to Treat Chemo-induced Neuropathy

There are different causes for neuropathy and effective treatment depends on identifying the underlying cause. One of the most common causes of neuropathy is diabetes.

Neuropathy usually causes pain and numbness in the hands and feet. It can result from traumatic injuries, infections, metabolic disorders, toxins and some kinds of treatment for lymphoma. 

There is no specific length of time that the pain exists, but symptoms often improve with time. 

Neuropathy is also associated with poor nutrition (vitamin b deficiency), certain diseases, direct injury, but many cases have no known reason (called idiopathic neuropathy).

A cautionary note:

It's reported that mega-doses of vitamin b-6 (pyridoxine) can cause sensory neuropathy, so best to consult an informed neurologist and avoid practicing medicine on oneself.

Pyridoxine (vitamin B6) toxicity courtesy of your local health food store
C D Silva and D P D'Cruz http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1798481/

Chemotherapy-induced Peripheral neuropathy (PN) is experienced as the loss of feeling in limbs and extremities. CIPN is probably caused when damage occurs to the myelin sheath, the "insulation" covering the nerve endings. PN is also caused by other conditions, such as HIV, and diabetes. 

Peripheral Neuropathy can be prevented or its progression slowed. By recognizing the early signs and symptoms, you can get prompt diagnosis, adjustment of cancer treatment, and treatment for the condition.

Clinical course:  Patients report that chemotherapy-caused neuropathy can improve with time. It may take a year or more after treatment to see improvement. 

"The onset and resolution of symptoms is variable. Some drugs may cause symptoms during or immediately after the first dose.

... The severity of symptoms is related to the cumulative dose of the drug received.1,2 Patients with pre-existing peripheral neuropathy may be at risk for a more severe and long-lasting neuropathy.

It is unclear what proportion of patients have a complete resolution of symptoms or how long it takes for symptoms to resolve because there are no published studies that have examined these questions.

However, many patients report to their health care providers that their symptoms improve or totally resolve over time. "  


In the News

Big news - ASCO: Cymbalta Tames Post-Chemo Pain http://bit.ly/1rpT0GO 
Study of interest: Tetrodotoxin for Pain Resulting From Chemotherapy
 - ClinicalTrials.gov http://1.usa.gov/170yO6k
Neuropathic Pain - Med News Today: (company press release)
KRN5500 Demonstrated Significant Decrease In The Intensity
Of Neuropathic Pain In Patients With Cancer
Patient tip: for neuropathy effecting your feet ... a shoe called Spenco

Jackie wrote: I too suffer from neuropathy in my feet. The pain was so bad at times I couldn't feel my feet at all and would stumble. The would feel so cold they burned. I was told a shoe called Spenco may helped....they have! They make sandals and a type of slip on canvas shoe that resembles Toms shoes (if you are familiar with them). The pain is still a problem, but the shoes are so comfortable and give my feet so much support that makes it easier to walk. They are a little pricey, but you can find them at several different websites and price compare. I hope this helps a little.  (Seems worth a try. We have no financial conflict of interest to disclose)

Drugs with Risk of this Side Effect:

Chemotherapeutic agents used to treat hematologic and solid tumors target a variety of structures and functions in the peripheral nervous system, including the neuronal cell body, the axonal transport system, the myelin sheath, and glial support structures. ”

Vincristine (part of CHOP)

Symptoms of PN may occur in individuals who clear this drug too slowly,
leading to increased concentrations of the drug in the blood.

Please report PN symptoms to your oncologist when they occur.

Cisplatin (Platinol®)

Carboplatin (Paraplatin®)

Oxaliplatin (Eloxatin®)

Adcetris (Brentuximab Vedotin)

ADCETRIS treatment causes a peripheral neuropathy that is predominantly sensory. Cases of peripheral motor neuropathy have also been reported. ADCETRIS-induced peripheral neuropathy is cumulative. In the HL and sALCL clinical trials, 54% of patients experienced any Reference ID: 3359579 grade of neuropathy. Of these patients, 49% had complete resolution, 31% had partial improvement, and 20% had no improvement. Of the patients who reported neuropathy, 51% had residual neuropathy at the time of their last evaluation. Monitor patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain or weakness. Patients experiencing new or worsening peripheral neuropathy may require a delay, change in dose, or discontinuation of ADCETRIS [see Dose Modification (2.2)].

Full prescribing information (Label): accessdata.fda.gov/
Velcade - Bortezomib-Induced Peripheral Neuropathy (BIPN)

Incidence and severity of bortezomib-induced PN BIPN was first reported in phase I trials.24 ... Among patients who developed PN, a full resolution or an improvement of the PN was reported in most of the patients during follow-up (in 51% of the patients with grade ≥2 PN, and in 71% of the patients with grade 3, 4 PN or with PN resulting in treatment discontinuation).

The median time to improvement or resolution of the PN was 47 (range, 1–529) days. Among patients without PN in the SUMMIT/CREST trials, 41 were included in the extension of the SUMMIT trial: only 5 (12%) of these patients presented PN after the additional courses of bortezomib. In spite of a prolonged treatment, most of the patients who had presented a PN in the SUMMIT/CREST trials did not report an aggravation of the PN, demonstrating that prolonged exposure to bortezomib does not increase the incidence or severity of the PN.14

Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2817035/

Symptoms: (will depend on severity)

Balance problems, decreased reflexes
Deep soreness or shooting pains in the muscles of the legs and lower arms that may
come and go, but always affect the same general area
Hyperensitivity to heat and cold
Electric shock sensation
Numbness, loss of sensation
Scab-like sensation when something touches their fingers or toes
Trouble swallowing
Severe cases: 

touching the affected area can feel like touching an open wound
Severe pain and altered feedback in the nervous system may even interfere with walking

Areas Affected:

Fingers and toes (most common)

This may move gradually upward in a stocking-glove type fashion.
May cause or worsen constipation, or lead to conditions such as ileus (intestinal blockage).
Other: face, back, chest.

Source:  Numbness & Tingling chemocare.com

NOTE: Please consult a pain specialist when experiencing severe levels of pain. 

neuropathy.org  to help locate a specialist in your area.

Avoiding secondary injuries:

Physical & occupational therapists can help you to minimize the risks associated with loss of feeling, which can limit your balance, strength, and ability to sense temperatures.
Here are some simple precautions to minimize the risks of injury:
Wear shoes to reduce the risk of falling.
Use sharp tools and objects with care.
Wear gloves when you do work activities (cleaning, gardening)
Provide adequate lighting

Use a night light
Use non-skid surfaces in bathroom and shower.
Keep floors and stairs free of objects.
Use handrails.
Tape the edges of throw rugs.
Test the temperature of the water before bathing or dish washing.
Check your shoes for how they fit and for small objects, such as pebbles
Look for any redness or blisters that you may not feel.


Treating Chemotherapy-related Peripheral Neuropathy (CIPN)? 

BIG NEWS: 2014, ASCO: Cymbalta Tames Post-Chemo Pain http://bit.ly/1rpT0GO 
Therapy of chemotherapy-induced peripheral neuropathy onlinelibrary.wiley.com/full

"The usual course of CIPN is symptoms that start during chemotherapy and then tend to improve after therapy is completed (Kannarkat et al, 2007).

Most CIPN improves after the offending drug is stopped (i.e. bortezomib and thalidomide), however, cisplatin CIPN may progress after the drug has been withdrawn (Windebank, 1999).

The type of neuropathy may vary with different drugs, and it is important to note what types of neuropathy are associated with the common offending agents (Table II). If the type of neuropathy seen clinically does not match with the expected neuropathy, the clinician should investigate for other causes.

Symptomatic treatments aim to relieve the symptoms of CIPN in patients who have already developed it after receiving neurotoxic drugs. This is a problem in all patients with PN, regardless of aetiology. Therefore, the majority of trials have been performed in the most frequently seen symptomatic neuropathies, especially those related to diabetes mellitus, and most agents tried have been anticonvulsants or antidepressants.

Unfortunately, when these data are extrapolated to CIPN, neither group of drugs has worked well to relieve the symptoms of CIPN. This may be due to the different qualities and pathophysiologies of toxic CIPN compared with other aetiologies.
Neuropathic Pain - Med News Today: (company press release)
KRN5500 Demonstrated Significant Decrease In The Intensity
Of Neuropathic Pain In Patients With Cancer
Physical Therapy to Improve Functionality in Peripheral Neuropathy Patients
James Nussbaum, Ph.D., M.S.P.T., C.S.C.S., E.M.T.
Chemotherapy-induced Peripheral Neuropathy Fact Sheet http://bit.ly/jyDcfb 

“Spotlight on Physical Therapy and Chemotherapy Induced Peripheral Neuropathy

“Three studies have examined progressive resistive exercise, aerobic exercise, and stretching exercises in the treatment of peripheral neuropathy. All three found significant improvements in outcomes such as stance, functional reach, and peroneal motor conduction velocity (Balducci et al., 2006; Lindeman et al., 1995; Richardson et al., 2001). A Cochrane review examined the role of exercise for individuals with peripheral neuropathy from etiologies other than chemotherapy. The study found that exercise increased function, muscle strength, endurance, quality of life and return to work. Strengthening exercises were found to reverse the losses in muscle strength related to peripheral neuropathy.”
Antioxidants such as alpha lipoic acid to prevent PN?

"Because it is a powerful antioxidant, there are concerns that lipoic acid could make radiation therapy or chemotherapy less effective. While this concern is based largely on theories of how cancer treatments work, it is supported by some recent studies. For this reason, people being treated for cancer should speak with their doctors before taking this supplement." cancer.org

So far there is no evidence from controlled clinical trials to show therapeutic or protective effects of alpha-lipoic acid. Clinical studies of sufficient size are required to determine the risks and potential benefits of any intervention, particularly when the effects are modest or small.
Report your symptoms so the treatment dose can be adjusted.

Please do not self-treat with vitamins, for which there is no clinical evidence.
Find Board Certified Neurologist application.abpn.com

The American Board of Psychiatry and Neurology, Inc. (ABPN) is a not-for-profit corporation dedicated to serving the public interest and the professions of psychiatry and neurology  by promoting excellence in practice through certification and maintenance of certification  processes. The ABPN is a Member Board of the American Board of Medical Specialties (ABMS).
Chronic pain treatments work better together eurekalert.org 

"When given both an anti-seizure drug (gabapentin) and an antidepressant (nortriptyline), patients suffering from neuropathic pain caused by nerve damage or disease experienced less pain than when they took one or the other individually, reports Ian Gilron"

2008 - Review:Chemotherapy-induced peripheral neuropathy: Prevention and treatment strategies PDF

Sherry Wolf *, Debra Barton, Lisa Kottschade, Axel Grothey, Charles Loprinzi Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA



What are the symptoms of chemo-induced PN? cancer.org
Chemotherapy-induced Peripheral Neuropathy Fact Sheet  cancersupportivecare.com
Numbness & Tingling chemocare.com
About Neuropathy neurologychannel 
Find a doctor who specializes in Neuropathy  neuropathy.org 
Management of Sensory Neuropathy  thebody
Venlafaxine Helpful in Painful Polyneuropathy CME News Author: Laurie Barclay, MD
CME Author: Bernard M. Sklar, MD, MS  Medscape (free login req.)
Vincristine (a cancer drug): raised level of serum alkaline
phosphatase may predict severe neurotoxicity

Can severe vincristine neurotoxicity be prevented? Cancer Chemother Pharmacol. 1982;8(2):211-4.
PMID: 6125275 | Related articles
Vincristine: Can its therapeutic index be enhanced?  http://onlinelibrary.wiley.com/doi/10.1002/pbc.22161/a

Quick Reference

Side effect of some 
chemo agents.

Experienced as a loss of feeling in limbs and extremities

May improve with time.

Difficult to treat.

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Research News

Chronic pain treatments work better together, says anesthesiologist eurekalert.org 

"When given both an anti-seizure drug (gabapentin) and an antidepressant (nortriptyline), patients suffering from neuropathic pain caused by nerve damage or disease experienced less pain than when they took one or the other individually, reports Ian Gilron"
Toxic neuropathy in patients with pre-existing neuropathy.
Neurology. 2003 Jan 28;60(2):337-40. PMID: 12552058  PubMed
Burning mouth syndrome (BMS) ("which has features of a neuropathy"): double blind controlled study of alpha-lipoic acid (thioctic acid) therapy. J Oral Pathol Med. 2002 May;31(5):267-9. PMID: 12110042  PubMed
Oxidative stress and diabetic neuropathy: pathophysiological mechanisms and treatment perspectives. Diabetes Metab Res Rev. 2002 May-Jun;18(3):176-84. PMID: 12112935  PubMed
Insulin-like growth factor I reverses experimental diabetic autonomic neuropathy. Am J Pathol. 1999 Nov;155(5):1651-60. PMID: 10550321  PubMed 
Caution: Insulin-like growth factor induces the survival and proliferation of myeloma cells through an interleukin-6-independent transduction pathway. Br  J Haematol. 2000 Nov;111(2):626-34. PMID: 11122111 PubMed
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For all medical concerns,  you should always consult your doctor. 
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