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TOPICS
Introduction | Symptoms | Drugs that Cause | In the News
Tips to avoid secondary injuries | Prevention | Treating Neuropathy| Resources | Research News
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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 will persist, but symptoms often improve with time.
Some forms of neuropathy are associated with poor nutrition (vitamin b deficiency), certain diseases, direct injury, but many cases have no known reason (called idiopathic neuropathy).
Chemotherapy-induced Peripheral Neuropathy (CIPN) can cause severe pain and can affect your ability to do things like walk, write, button your shirt, or pick up coins. If it gets very bad, it can cause more serious problems.
Reporting neuropathy to your physician when on treatment
Talk to your doctor or nurse right away about any symptoms of CIPN that you have. They’ll want to watch you closely to see if the problems get worse. They may need to modify your treatment plan.
Ask your doctor: "What symptoms do I need to watch for and report to you?"
Source: www.facit.org to download and print.
Note: The side effects of cancer drugs can vary from person to person. In some persons a very slow clearance of the drug may cause too much exposure leading to side effects. Your doctor cannot know about this side effect unless you report it to him or her. The dose or schedule of the drug causing neuropathy can be modified based on the severity of the symptoms that you report.
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.
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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/
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Chemotherapy-induced Peripheral neuropathy (CIPN) 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. "
Source: cancersupportivecare.com
In the News
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URCC NCORP nationwide randomized controlled trial investigating the
effect of exercise on chemotherapy-induced peripheral neuropathy in 314 cancer patients.
2016 ASCO Annual Meeting http://bit.ly/28J5ZS5
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"Calmare therapy" in for cancer-related neuropathic pain:
Exploratory pilot study. - PubMed - NCBI http://1.usa.gov/28RzUM8
Predictive factors associated with success outcomes for Calmare (Scrambler) therapy: a multicenter analysis. http://1.usa.gov/28NZjVg
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Natural products & complementary therapies for chemo-induced peripheral neuropathy: -
Abstract - Europe PMC http://bit.ly/1UbldVg
SNIP: Of 1465 publications screened, 12 RCTs evaluated natural products and one evaluated electroacupuncture. Vitamin E may help prevent CIPN. l-Glutamine, goshajinkigan, and omega-3 are also promising. Acetyl-l-carnitine may worsen CIPN and alpha-lipoic acid activity is unknown. Electroacupuncture was not superior to placebo. No RCTs were published regarding other complementary therapies, although some studies mention positive incidental findings.
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ASCO: Cymbalta Tames Post-Chemo Pain http://bit.ly/1rpT0GO
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Study of interest: Tetrodotoxin for Pain Resulting From Chemotherapy
- ClinicalTrials.gov http://1.usa.gov/170yO6k
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Neuropathic Pain - Med News Today: (company press release)
KRN5500 Demonstrated Significant Decrease In The Intensity
Of Neuropathic Pain In Patients With Cancer
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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)
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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. ”
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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.
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PLATINUM COMPOUNDS:
Cisplatin (Platinol®) | Carboplatin (Paraplatin®) | Oxaliplatin (Eloxatin®)
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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/
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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/
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Symptoms: (will depend on severity of the PN)
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Balance problems, decreased reflexes
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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
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Hyperensitivity to heat and cold
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Electric shock sensation
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Numbness, loss of sensation
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Scab-like sensation when something touches their fingers or toes
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Trouble swallowing
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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
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Areas Affected:
NOTE: Please consult a pain specialist when experiencing severe levels of pain.
See 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:
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Wear shoes to reduce the risk of falling.
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Use sharp tools and objects with care.
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Wear gloves when you do work activities (cleaning, gardening)
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Provide adequate lighting
Use a night light
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Use non-skid surfaces in bathroom and shower.
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Keep floors and stairs free of objects.
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Use handrails.
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Tape the edges of throw rugs.
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Test the temperature of the water before bathing or dish washing.
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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.
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Prevention of Peripheral Neuropathy (CIPN)?
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URCC NCORP nationwide randomized controlled trial investigating the
effect of exercise on chemotherapy-induced peripheral neuropathy in 314 cancer patients. 2016 ASCO Annual Meeting http://bit.ly/28J5ZS5
Results: Exercise reduced CIPN compared to control (p = 0.04, effect size [ES] = 0.26, ANCOVA).
Older patients benefitted more from exercise than younger patients, compared to control (p = 0.06, ES= 1.05 for ages 28-47 vs. ages 64-79).
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Treating Chemotherapy-related Peripheral Neuropathy (CIPN)?
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"Calmare therapy" in for cancer-related neuropathic pain:
Exploratory pilot study. - PubMed - NCBI http://1.usa.gov/28RzUM8
Predictive factors associated with success outcomes for Calmare (Scrambler) therapy: a multicenter analysis. http://1.usa.gov/28NZjVg
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2014, ASCO: Cymbalta Tames Post-Chemo Pain http://bit.ly/1rpT0GO
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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.
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Neuropathic Pain - Med News Today: (company press release)
KRN5500 Demonstrated Significant Decrease In The Intensity
Of Neuropathic Pain In Patients With Cancer
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Physical Therapy to Improve Functionality in Peripheral Neuropathy Patients
James Nussbaum, Ph.D., M.S.P.T., C.S.C.S., E.M.T.
http://bit.ly/iNxy6X
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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.”
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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
http://lymphomation.org/CAM-A-E.htm#lipoic
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.
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Report your symptoms so the treatment dose can be adjusted.
Please do not self-treat with vitamins, for which there is no clinical evidence.
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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).
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Neurologychannel.com
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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"
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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
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Resources:
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What are the symptoms of chemo-induced PN? cancer.org (fixed 6/22/16)
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Chemotherapy-induced Peripheral Neuropathy Fact Sheet cancersupportivecare.com
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Numbness & Tingling chemocare.com
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About Neuropathy neurologychannel
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Find a doctor who specializes in Neuropathy neuropathy.org
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Management of Sensory Neuropathy thebody
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Venlafaxine Helpful in Painful Polyneuropathy CME News Author: Laurie Barclay, MD
CME Author: Bernard M. Sklar, MD, MS Medscape (free login req.)
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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
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Vincristine: Can its therapeutic index be enhanced? http://onlinelibrary.wiley.com/doi/10.1002/pbc.22161/a
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