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Chemotherapy-induced Peripheral Neuropathy Fact Sheet
Meredith A. Wampler, PT, DPTSc and Ernest H. Rosenbaum, MD


What is chemotherapy-induced peripheral neuropathy (CIPN)?
Chemotherapy-induced peripheral neuropathy describes damage to the peripheral nervous system, the system that transmits information between the central nervous system (e.g. the brain and spinal cord) and the rest of the body, caused by some chemotherapy agents. Commonly used chemotherapy agents associated with peripheral neuropathy are listed in Table 1.

What are the symptoms of CIPN?
Symptoms are related to the type of nerve that is affected by the chemotherapy. Sensory nerves are at increased risk to chemotherapy associated damage compared to motor nerves. This is because most of the drugs associated with CIPN are not able to enter the well-protected central nervous system, where the cell bodies (the location of important cell sustaining functions) of motor nerves are located. Therefore, patients often experience sensory symptoms such as numbness, tingling, or burning sensations. Patients may also notice that things that are not normally painful are now painful (called allodynia). For example, after receiving cisplatin, some people report that touching cold things or cold breezes over the skin are painful (CITE). In addition, patients may develop decreased sense of vibration, diminished or absent reflexes.1-3 Sensory symptoms often begin in the tips of the fingers or toes and may progress into a stocking and glove pattern. While it is less common, some people can develop weakness.2 Symptoms are described by drug class in Table1.

The onset and resolution of symptoms is variable. Some drugs may cause symptoms during or immediately after the first dose. The platinum compounds have been reported to have a delayed onset of symptoms, up to several weeks after the last 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.

Table 1. Commonly used chemotherapy agents associated with peripheral neuropathy
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Class of chemotherapy agent Incidence of Peripheral Neuropathy Sensory Symptoms Motor Symptoms
Taxane Class:
Paclitaxel (Taxol®)
Docetaxel (Taxotere®)
AbraxaneTM
60%6
50%6
71%7
Mild to moderate numbness, tingling, burning/stabbing pain of hands and feet are common which can become severe with increased doses.8,9 Reduced or absent achilles tendon reflex.4 Weakness of distal muscles has been documented with high cumulative doses of paclitaxel and docetaxel.5
Vinca Alkaloid Class:
Vincristine (Onkovin®)
Vinorelbine (Navelbine®)
Not listed
25%8
Mild to moderate numbness, tingling, burning/stabbing pain of hands and feet are common and can become severe with increased doses.8,9 Reduced or absent Achilles tendon reflex.4 Weakness of distal muscles, decreased deep tendon reflexes, and foot drop have been noted with high doses.8,9
Platinum Compounds:
Cisplatin (Platinol®)
Carboplatin (Paraplatin®)
Oxaliplatin (Eloxatin®)
Not listed
4%10
74%11
Mild to moderate numbness and tingling of hands and feet can occur after prolonged (4-6 months) of therapy and may develop 3-8 weeks after last dose.12 Symptoms can become severe with high cumulative doses.12 Reduced or absent Achilles tendon reflex.1 Weakness is rare but can occur with high doses of Cisplatin and Oxaliplatin.11,12

Will CIPN affect physical function in day to day activities?
CIPN has been associated with changes to physical function. Patients who were treated for breast cancer with Taxol or Taxotere were found to have problems with their balance and required more time to perform a short walking task.3,13 Patients may notice that they trip or stumble when walking. They may also not feel steady on uneven surfaces (like rocky hiking trails or gravel roads) or feel that they need to hold onto a handrail as they go up or down stairs. Other studies have found that patients with painful CIPN had more difficulty with fine motor task of their hands. 14 They may also notice difficulty with writing or typing on a keyboard.

How is CIPN diagnosed?
Be sure to report your symptoms to your physicians and/or nurse. This is helpful, because not everyone who takes the above drugs will experience CIPN. In addition, it has been found that patients will often rate their symptoms as being more severe than what their health care providers would rate them15. This is because many of the symptoms of CIPN are subjective making it is difficult for health care providers to know how these symptoms are affecting you. Once your health care provider is aware that you are experiencing symptoms, they can use other tools to monitor the severity of CIPN. There are many ways to measure peripheral neuropathy. Following is a partial list of tools that have been reported to be sensitive in detecting CIPN.

Total Neuropathy Score (TNS)4
A composite score (0-32 points) combining subjective sensory symptoms, subjective report of symptoms and amount of difficulty with daily activities, deep tendon reflexes, manual muscle testing of muscles for the wrist and ankle, pin sensibility, quantitative vibration thresholds (the ability to feel vibration), and nerve conduction studies of sural and peroneal nerves (one sensory and one motor nerve in the leg).

Nerve Conduction Studies
This test is often performed by a neurologist. They will stimulate the nerve with an electrical impulse and measure how long it takes the impulse to reach a recording instrument at a specific distance from where the nerve was stimulated. They will also measure how strong the impulse is when it reaches the recording site. This is usually done with pads that are stuck to the skin.

Modified Total Neuropathy Score(mTNS)16
Same procedures as the TNS, except nerve conduction studies are excluded.

Michigan Diabetic Neuropathy Scale (MDNS)17
A composite score (0-44 points) combining touch using a 10-gram monofilament, vibration using a 110-Hz tuning fork, pin sensibility using a safety pin, strength using manual muscle tests, and deep tendon reflex tests. Can also add nerve conduction studies, but the MDNS can be scored without nerve conduction studies. A cost effective alternative to the mTNS if you do not have a piece of equipment (such as a Biothesiometer) to perform quantitative vibration testing in your clinic.

Semmes Weinstein Monofilaments (SWM)16
A method to establish light touch thresholds on the pad of the great toe and the pad of the index finger. More proximal test sites could be beneficial if the neuropathy is more severe. A full set of 20 SWM will provide the tester with a means to test small changes in touch thresholds.

Biothesiometer® (Bio-Medical Instrument Company, Newbury, OH)16,18
A machine that has a hand held device that vibrates at a constant frequency (120Hz) and allows the tester to adjust the amplitude of the vibration. The amplitude of vibration is quantified by the change in the voltage of the machine as the tester turns the dial of the Biothesiometer. Allows the tester to establish a quantitative vibration threshold.

World Health Organization Common Toxicity Criteria for Peripheral Neuropathy19
A 4-point scale that rates the severity of sensory and motor symptoms and includes an examination of deep tendon reflexes. Patients with a score of 0 have no neuropathy, and patients with a score of 4 have severely debilitating symptoms or paralysis.

Pain Quality Assessment Scale20
A 20-item questionnaire (0-200 points) developed to quantify the quality and intensity of neuropathic pain.

Fact-Taxane21
A questionnaire (0-172 points) that assesses the quality of life of patients being treated with the taxane class of chemotherapy drugs. There are five aspects of this questionnaire: emotional well-being, functional well-being, physical well-being, social/family well-being, and severity of symptoms specific to taxane therapy.

What treatments are available?
There are many treatments available to improve the symptoms and functional problems associated with CIPN. While there are no clinical trials showing the effectiveness of these treatments specifically for patients with CIPN, there is evidence that these treatments are effective for patients with similar problems.

Pain
Your physician or nurse practitioner may prescribe analgesics to alleviate painful symptoms. Gloves, scarves, hats, socks, or other protective clothing can be used to protect the skin from painful stimulation from normally non-painful stimuli (such as cold breezes or the brush of bed sheets across your toes).

Physical Function
Your physician or nurse practitioner may refer you to physical therapy for further assessment and treatment of balance problems and problems with hand function. They may recommend a sensory retraining program or an exercise-based program to help improve these problems. In addition, they have training to help determine if you would benefit from assistive devices, such as elastic shoe laces, button hooks, or grip build up for writing utensils.

Sensory and Motor Symptoms
At this time, there are no effective treatments to reverse or prevent CIPN symptoms such as numbness, tingling, or diminished reflexes. Fortunately, peripheral nerves are able to repair themselves and therefore many people have resolution of their symptoms over time. However, if the damage is too severe, patients may have persistent symptoms. It is unclear at this time the factors that predict who is at risk for severe and/or persistent CIPN.



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First appeared October 28, 2005; updated April 2, 2008