• cancer;
  • rehabilitation;
  • survivorship;
  • neuropathy;
  • chemotherapy;
  • radiculopathy;
  • brachial plexopathy;
  • breast cancer;
  • surveillance;
  • pain;
  • palliative care


  1. Top of page
  2. Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) results from damage to or dysfunction of the peripheral nerves. The development of CIPN is anticipated for the majority of breast cancer patients who receive neurotoxic chemotherapy, depending on the agent used, dose, and schedule. Sensory symptoms often predominate and include numbness, tingling, and distal extremity pain. Weakness, gait impairment, loss of functional abilities, and other deficits may develop with more severe CIPN. This article outlines a prospective surveillance model for physical rehabilitation of women with breast cancer who develop CIPN. Rehabilitative efforts for CIPN start at the time of breast cancer diagnosis and treatment planning. The prechemotherapy evaluation identifies patients with preexisting peripheral nervous system disorders that may place them at higher risk for the development of CIPN. This clinical evaluation should include a history focusing on symptoms and functional activities as well as a physical examination that objectively assesses the patient's strength, sensation, reflexes, and gait. Ongoing surveillance following the initiation of a neurotoxic agent is important to monitor for the development and progression of symptoms associated with CIPN, and to ensure its resolution over the long term. CIPN is managed best by a multidisciplinary team approach. Early identification of symptoms will ensure appropriate referral and timely symptom management. The prospective surveillance model promotes a patient-centered approach to care, from pretreatment through survivorship and palliative care. In this way, the model offers promise in addressing and minimizing both the acute and long-term morbidity associated with CIPN. Cancer 2012;. © 2012 American Cancer Society.

There are an estimated 2.8 million breast cancer survivors in the United States, representing by far the largest proportion (44%) of female cancer survivors.1 With 41% of new cases diagnosed in women aged 65 and older, and overall 5-year survival rates nearing 90%, (98% for localized tumors), the number of breast cancer survivors is expected to increase dramatically in future years.1 Although the high rate of women surviving for years beyond their breast cancer is encouraging, it also means that more of them are living with the chronic and late effects of cancer treatment or with advanced disease. This article outlines a prospective surveillance model for physical rehabilitation of women with breast cancer who develop chemotherapy-induced peripheral neuropathy (CIPN). To adopt this model, it is imperative that clinicians understand the importance of identifying patients with preexisting peripheral nervous system (PNS) disorders that may place them at higher risk for the development of CIPN when challenged with neurotoxic chemotherapy and the other disorders that mimic CIPN.

CIPN results from damage to or dysfunction of the peripheral nerves that connect the brain and spinal cord with the rest of the body. These nerves include the motor, sensory, and autonomic nerves. The symptoms experienced by a breast cancer survivor will vary depending on which of these types of nerves are affected and how severely. Many women present with sensory symptoms such as numbness, tingling (one type of paresthesia; a spontaneous or evoked abnormal sensation that is not unpleasant or painful), cold sensitivity, or the sense that they are wearing gloves and stockings, whereas others report varying degrees of pain. Pain often includes dysesthesias (a spontaneous or evoked abnormal unpleasant sensation) or allodynia (what should be normal touch perceived as painful) and can be described as burning, freezing, lancinating, shock-like, or electric in nature.2 Autonomic nerve involvement can result in diarrhea or constipation, orthostatic symptoms, and irregular heartbeat. Less commonly, women may report motor problems including lower limb weakness, impaired proprioception, and functional impairments that compromise the ability to walk or carry items, increase falls, interfere with activities of daily living (ADLs), and decrease quality of life.2 In some cases, CIPN can be a dose-limiting factor for certain chemotherapeutics or delay treatment, thereby influencing survival.2, 3

The incidence of CIPN in women receiving chemotherapy for breast cancer is not well-established, because there is no gold standard method of assessment.4, 5 The neurotoxic chemotherapeutic agents commonly used in the treatment of early stage or advanced breast cancer include the taxanes (paclitaxel, docetaxel), the vinca alkaloids (vinorelbine), the platinum analogues (cisplatin, carboplatin), and the antimetabolites (capecitabine).3, 6, 7 At present, taxanes are the only neurotoxic chemotherapeutic routinely used in the neoadjuvant and adjuvant setting. Ongoing investigation into the use of platinum-based regimens in the treatment of triple-negative breast cancers (a subgroup that do not express the estrogen receptor, progesterone receptor, or human epidermal growth factor receptor type 2) has shown promise.8, 9 Otherwise, the neurotoxins are relegated to the treatment of metastatic breast cancer.

The National Comprehensive Cancer Network convened a task force to guide the management of neuropathy in cancer.2 Their report reviews the incidence of CIPN across studies; although these incidence estimates are based on survivors of breast and other cancers, the magnitude of the difference in incidence among the agents is instructive. Among the taxanes, the incidence of CIPN among those treated with paclitaxel is high (57%-83% overall; 2%-33% severe), whereas estimates associated with docetaxel are more variable (11%-64% overall; 3%-14% severe). The incidence of CIPN among those treated with vinca alkaloids ranges from 30% to 47%, whereas the incidence among those treated with cisplatin ranges from 28% to 100%. The risk of CIPN with administration of capecitabine alone is unknown; however, the incidence of CIPN associated with capecitabine in combination with the microtubulin-targeting agent ixabepilone is 67% (21% severe).2 A combination of paclitaxel and carboplatin caused CIPN in 67% of patients with solid tumors in a small, prospective study.10

More research elucidating the risk factors for the development of CIPN is needed to aid clinicians in identifying those individuals at highest risk for acute and chronic syndromes. Many cancer survivors may be predisposed to the development of neuropathy or neuropathic symptoms from non–cancer related PNS disorders. For example, age, diabetes, alcohol use, and nonalcoholic liver disease are associated with increased risk for neuropathy independent of cancer.11 Patients with the hereditary neuropathy Charcot-Marie-Tooth are poorly tolerant of neurotoxic chemotherapeutics including vincristine and paclitaxel.12, 13 Similarly, the presence of diabetes mellitus has the potential to increase the risk not only of CIPN but also autonomic neuropathy in patients who are challenged with neurotoxic chemotherapy.14–17 A history of prior exposure to neurotoxic chemotherapy also likely predisposes the patient to the development of neurotoxicity when they are challenged with additional neurotoxic chemotherapy.18–20 Although little supportive evidence is available in the literature, degenerative disorders such as nerve root compression from lumbar spinal stenosis and carpal tunnel syndrome (median mononeuropathy at the wrist) may manifest or worsen clinically when patients are exposed to neurotoxic chemotherapeutics. To an untrained clinician, such disorders can mimic a CIPN, or a more severe neuropathy than the patient in fact has.

With taxane-based chemotherapy, the onset of CIPN symptoms often involves acute tingling in the fingertips and toes occurring within 24 hours of infusion.21 The severity of neuropathy increases with the dose and duration (number of cycles) of exposure.22 This pattern is similar for vinca alkaloids with the exception of the rare occurrence of coasting phenomenon, where the neuropathy can worsen weeks to months after exposure.3 The coasting phenomenon is more common with the platinum analogues, particularly cisplatin.3 Capecitabine is associated with a small-fiber neuropathy.6 For most cancer survivors, these symptoms subside in weeks to months. Some patients, however, face long-term problems related to CIPN. For example, in one study of breast cancer survivors treated on average 9 years prior with paclitaxel, 27% diagnosed with CIPN during treatment had progressed to have a posttreatment neuropathic pain syndrome.23


  1. Top of page
  2. Abstract

Diagnosis of Neuropathy

Baseline assessment

Rehabilitative efforts start with breast cancer diagnosis and treatment planning. Figure 1 outlines a neuropathy assessment algorithm for assessment of breast cancer patients before and during administration of neurotoxic chemotherapy. Preexisting or subclinical neuromuscular and other disorders that are likely to manifest or worsen during the course of breast cancer treatment should be identified. In those instances where the etiology of signs and symptoms are not apparent, they should be clarified with further investigation as appropriate. Patients should be educated about any preexisting nerve dysfunction that is identified and counseled on the possibility of their developing nerve dysfunction with certain chemotherapeutic agents. Furthermore, they should be assured that they will be followed closely for, among other things, the development of CIPN.

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Figure 1. Diagram shows neuropathy assessment algorithm used before and during administration of neurotoxic chemotherapy for breast cancer.

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The presence of PNS disorders such as polyneuropathy from diabetes or other causes, radiculopathy from spinal stenosis, plexopathy, mononeuropathy (ie, carpal tunnel syndrome, peroneal neuropathy), hereditary neuropathies, and so forth, should be identified prior to initiation of neurotoxic chemotherapy. These disorders often have subtle or subclinical signs and symptoms that may worsen significantly when challenged with neurotoxic chemotherapy. Such knowledge may prompt the treating oncologist to choose a neurotoxin-sparing regimen such as cyclophosphamide/methotrexate/fluorouracil (CMF) instead of docetaxel/doxorubicin/cyclophosphamide (TAC), if they consider the oncologic outcome to be equivalent.7 Many of these disorders are quite common. Diabetic peripheral neuropathy, for instance, may affect 50% of people with diabetes mellitus and cause neuropathic pain in 11%.24 Distal symmetric polyneuropathy has an overall prevalence of ≈2400 per 100,000 (2.4%) in the general population but rises to ≈8000 per 100,000 (8%) in individuals older than 55 years of age.25, 26 In one study, the reported annual incidence of lumbar spinal stenosis was approximately 5 cases per 100,000 with 58% of these patients having claudication, 35% radicular pain, and 7% mixed symptoms.27

The diagnosis of neuropathy and PNS starts with a clinical evaluation that includes a baseline history and physical evaluation. A major focus of the prechemotherapy assessment should be to identify PNS dysfunction. In addition, determination of the etiology of PNS pathology is critically important, because many disorders are treatable (ie, diabetes mellitus, chronic idiopathic demyelinating polyneuropathy) or even potentially reversible (ie, vitamin B12 deficiency).28–30 The basic components of the baseline clinical evaluation, including a baseline history and physical examination, are outlined in Figure 1.

In the majority of cases, no evidence of PNS dysfunction will be present on baseline assessment, and patients will receive chemotherapy at the discretion of their treating oncologist. For patients who exhibit signs and symptoms of PNS dysfunction, a comprehensive assessment by a physician (neurologist or rehabilitation medicine specialist/physiatrist) with specialized training in neuromuscular medicine (ie, certified by the American Board of Electrodiagnostic Medicine) should be considered (Fig. 1). The combination of medical history, neurologic examination, electrodiagnostic studies, and basic laboratory testing will yield an etiologic diagnosis in 74% to 82% of patients with polyneuropathy.30 If other disorders are suspected, the neuromuscular specialist can help guide additional laboratory testing, muscle or nerve biopsy, and imaging as appropriate. In addition, the neuromuscular specialist may offer valuable insights and assistance in managing neurologic deficits should they worsen during the course of therapy.

Assessment during chemotherapy

The development of mild to moderate signs and symptoms of CIPN is an anticipated consequence of exposure to neurotoxic chemotherapy for many, if not most, breast cancer patients in the adjuvant and neoadjuvant setting based on the incidence data presented above (57%-83% overall; 2%-33% severe for paclitaxel).2 Susceptibility and severity will depend on multiple factors including the patients comorbidities, the specific agent used, as well as the dose and schedule of administration.3 As with the prechemotherapy evaluation, a clinical evaluation by the treating oncologist or nurse practitioner that includes a history focusing on symptoms (pain, numbness, paresthesias) and functional activities (gait, ADLs) as well as a physical examination by a physical therapist that objectively assesses the patient's strength, sensation, reflexes, gait, and so forth, should determine if CIPN is developing. Such an assessment should be performed every 2 weeks or prior to each cycle of chemotherapy during the course of treatment if the patient reports symptoms of CIPN.

Many tools have been developed to assess CIPN.31 The current scales suffer from poor interobserver reliability and tend to underestimate and underreport the severity and frequency of CIPN, particularly subjective symptoms such as fatigue and numbness.31 The most commonly used tool to assess CIPN in clinical oncology is the Common Terminology Criteria for Adverse Events (CTCAE) scale developed by the Eastern Cooperative Oncology Group and the National Cancer Institute. The most recent version 4.03 was released in 2010 and is available at The CTCAE version 4.03 defines grade 1 paresthesias as mild symptoms; grade 2 as moderate symptoms that limit instrumental ADLs; and grade 3 as severe symptoms limiting self-care ADLs.32 Neurotoxic chemotherapy adjustments or delays may occur with the onset of grade 2 neurotoxicity. Table 1 lists the CTCAE version 4.03 definition and grading of peripheral motor and sensory neuropathy as well as radiculitis and brachial plexopathy. The definitions of instrumental and self-care ADLs from the document are also provided. Disorders of the nerve root (radiculitis) and plexus (brachial plexopathy) are listed, because these disorders, like others of the PNS, are prone to misdiagnosis as neuropathy by inexperienced observers, and the definitions provided in CTCAE version 4.03 offer little clarity. For instance, the definition of brachial plexopathy includes the terms “marked discomfort” and “limited movement in the arm or hand.” In fact, early brachial plexopathy can present as vague paresthesias in the hand that can present during treatment and mimic a CIPN, save for its distribution.

Table 1. Peripheral Nervous System Disorders and Their Definitions From the Common Terminology Criteria for Adverse Events, Version4.0312
Adverse EventGrade
  1. ADLs indicates activities of daily living.

  2. Instrumental ADLs refer to preparing meals, shopping for groceries or clothes, using the telephone, managing money, and so forth.

  3. Self-care ADLs refer to bathing, dressing, and undressing, feeding self, using the toilet, taking medications, and not bedridden.

Paresthesia : A disorder characterized by functional disturbances of sensory neurons resulting in abnormal cutaneous sensations of tingling, numbness, pressure, cold, and warmth that are experienced in the absence of a stimulus.Mild symptomsModerate symptoms; limiting instrumental ADLsSevere symptoms; limiting self-care ADLs  
Peripheral motor neuropathy: A disorder characterized by inflammation or degeneration of the peripheral motor nerves.Asymptomatic; clinical or diagnostic observations only; intervention not indicatedModerate symptoms; limiting instrumental ADLsSevere symptoms; limiting self-care ADLs; assistive device indicatedLife-threatening consequences; urgent intervention indicatedDeath
Peripheral sensory neuropathy: A disorder characterized by inflammation or degeneration of the peripheral sensory nerves.Asymptomatic; loss of deep tendon reflexes or paresthesiaModerate pain; limiting instrumental ADLsSevere pain; limiting self-care ADLsLife-threatening consequences; urgent intervention indicatedDeath
Radiculitis: A disorder characterized by inflammation involving a nerve root. Patients experience marked discomfort radiating along a nerve path because of spinal pressure on the connecting nerve root.Mild symptomsModerate symptoms; limiting instrumental ADLs; medical intervention indicatedSevere symptoms; limiting self-care ADLsLife-threatening consequences; urgent intervention indicatedDeath
Brachial plexopathy: A disorder characterized by regional paresthesia of the brachial plexus, marked discomfort and muscle weakness, and limited movement in the arm or hand.Asymptomatic; clinical or diagnostic observations only; intervention not indicatedModerate symptoms; limiting instrumental ADLsSevere symptoms; limiting self-care ADLs

Patients who develop mild (CTCAE version 4.03 grade 1) symptoms of CIPN generally require no special treatment in terms of neuromuscular intervention or evaluation. Often, their symptoms will resolve in time, usually within several weeks to months. Such patients should be referred for an early rehabilitation assessment to initiate an exercise program to prevent other morbidity such as upper extremity range-of-motion deficits. By the CTCAE version 4.03 definition, patients with grade 2 (moderate) motor or sensory neuropathy have limitations in their instrumental ADLs (preparing meals, shopping for groceries or clothes, using the telephone, managing money). Patients with grade 3 (severe) motor or sensory neuropathy have limitations in their self-care ADLs (bathing, dressing and undressing, feeding self, toileting, taking medications) but are not bedridden. Grade 2 and 3 CIPN represent significant functional limitation and require urgent rehabilitation intervention to address pain control and functional restoration. It is our strong recommendation that any patient with pain or functional impairment (decreased ADLs or self-care) should have their pain addressed and be immediately referred for rehabilitation services for functional restoration.

Treatment of Neuropathy


In patients undergoing neurotoxic cancer treatments, symptoms of CIPN may develop rapidly, leaving the patient little time to adapt.33 Early detection and timely intervention are paramount in maintaining a patient's safety and functional independence. Thus, patients should be educated on early signs and symptoms of CIPN and the need for reporting of symptoms to the health care team.34 Education should also include counseling of strategies for managing symptoms of CIPN (Table 2). An evidence-based review of interventions for CIPN highlighted the importance of patient education to reduce the risk of injury and falling.35 Recommendations included teaching the importance of vision as a compensatory strategy to maintain balance, as well as providing instruction in proper skin care, home modification to improve safety, and strategies to minimize effects due to autonomic dysfunction.35

Table 2. Strategies for Managing Symptoms Associated With Chemotherapy-Induced Peripheral Neuropathy
Dizziness• Change positions slowly to allow the body time to adjust2, 63
• Sit or lie down promptly if dizzy, get up slowly once the dizziness goes away63
• Dangle feet over the edge of your bed for about 20 to 30 seconds before getting up63
• Before standing up from sitting, wiggle toes and perform ankle circles63
• Wait for a few seconds after standing up before moving away from support or chair63
Falls prevention• Use vision to compensate for loss of sensation in feet and hands35
• Wear good fitting, stable footwear with good grip under surface35
• Pay close attention to walking surfaces35
• Balance and gait retraining by a physical therapist2
Skin protection• Inspect hands and feet daily for wounds or blisters35
Cold-induced sensitivity• Eat foods and beverages at room temperature36
• Avoid drinks with ice cubes and cold foods such as ice cream36
• Wear gloves or oven mitts when handling items from the fridge or freezer36
• Wear appropriate winter clothing such as warm socks, gloves, scarves, and caps36

Currently, there are no medications that can prevent or reverse CIPN. Contemporary strategies target positive symptoms (those occurring as a result of abnormal evoked or spontaneous neural activity) such as paresthesias and dysesthesia. These symptoms are often painful or uncomfortable for the patient. Negative neuropathic symptoms such as numbness or weakness cannot be reversed by medications but may improve spontaneously with time, physical or occupational therapy, and other modalities (Fig. 2). The primary pharmacological agents used to manage neuropathic pain include anticonvulsants, antidepressants, opioids, and local anesthetics.36 The rationale for the use of these agents has resulted primarily from established efficacy in painful diabetic neuropathy (PDN).37 Recent evidence-based guidelines systematically reviewing the literature on the treatment of PDN from 1960 through August 2008 concluded that there was high-level evidence establishing pregabalin as effective.38 Venlafaxine, duloxetine, amitriptyline, gabapentin, valproate, opioids (morphine sulfate, tramadol, and oxycodone controlled-release), and capsicine were considered probably effective and should be considered for treatment of PDN.3 In light of the complexity in managing pain and symptoms associated with CIPN, a task force report on neuropathy in cancer was published that includes recommendations on treatment strategies to guide clinicians.2

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Figure 2. Procedures for chemotherapy-induced peripheral neuropathy symptom management are shown.

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Neuromuscular electrical stimulation

Neuromuscular electrical stimulation modalities such as transcutaneous electrical nerve stimulation (TENS) and electrical stimulation (ES) have shown some benefit in managing pain related to diabetic peripheral neuropathy.39 In a meta-analysis of 3 randomized trials including 78 patients with diabetic peripheral neuropathy, reductions in pain scores were found to be significantly better after treatment with TENS than with placebo TENS.39 Although these results are promising, there was considerable heterogeneity among the 3 studies included in the meta-analysis; therefore, further randomized trials are needed to confirm this finding. In the only study that examined patients with CIPN, a patient-specific cutaneous ES device was found to reduce pain in a sample of 16 patients with refractory CIPN.40 To date, the evidence supporting the use of TENS and ES for CIPN is limited; however, given their low cost and risk profile, they are recommended as potential treatment options for patients with CIPN who are refractory to pain medication.2, 37

Physical functioning

The patient with sensory and motor effects from CIPN may have difficulty carrying out ADLs and maintaining functional independence. Aspects of function that are commonly impaired or compromised include balance and coordination, muscle performance, and mobility.2, 41 Interventions can be tailored to the patient's needs and may include therapeutic exercises and balance retraining, and the provision of gait aids, orthotics, and assistive devices.35

Physical therapists, as experts in physical functioning, can provide therapeutic interventions to remediate or compensate for deficits.34 Specific therapeutic exercises may be prescribed to address pain as well as impairments in range of motion, muscular strength, and balance. As an example, exercises may include active and passive range-of-motion exercises as well as targeted strengthening exercises for the distal extremities.42

The maintenance of an upright posture is highly dependent on feedback from the somatosensory system; therefore, sensory losses alone or in combination with motor neuropathy can greatly impair balance, gait, and overall function.41 CIPN in combination with postural hypotension, poor posture, muscular weakness, and preexisting deficits in vision may place the patient at even higher risk for loss of balance and falls.35, 43 In a recent study, risk of falling was associated with a number of factors, including higher doses of chemotherapy, more neuropathic symptoms, and more severe muscular weakness and loss of balance.43

Balance retraining involves the manipulation of variables such as the base of support, stance configuration, and walking surface to challenge the proprioceptive component of balance control.44 Balance retraining exercises are often started in 2-legged stance and progress to tandem or single-leg stance. To further challenge balance, exercises can be progressed from stable to unstable surfaces, and can involve perturbation training or multisensory challenges (eg, eyes open or eyes closed).45 Balance retraining has been shown to improve clinical measures of balance in patients with peripheral neuropathy.46, 47

Walking aids and assistive devices

The use of a gait aid such as a walking stick, walker, or cane may be recommended to help with balance and to address gait deficits.34 A brace such as an ankle-foot orthosis can compensate for lower extremity weakness deficits such as foot drop (dorsiflexion), protect an unstable ankle (inversion and/or eversion), and improve alignment and balance48 (Fig. 3). The use of gait aids and orthotics has been shown to improve gait in conditions with low lighting and uneven walking surfaces.47

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Figure 3. The use of a gait aid, such as the ankle-foot orthosis pictured, can help with balance and address gait deficits.

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A variety of assistive devices are available to improve function and efficiency when patients perform ADLs. Occupational therapists (OT) are specially trained to assess and treat upper extremity function, and an OT can evaluate the need for assistive devices and adaptive equipment to help the patient compensate for difficulties with tasks at home or work.49, 50 This may include the provision of adaptive equipment such as built-up handles on utensils, rubber nonslip handles, adaptive button hooks, and bathroom aids.50 In addition, the OT can also educate the patient on strategies to optimize function and to address safety in the home (Table 3).

Table 3. Protective Household Modification for Patients With Chemotherapy-Induced Peripheral Neuropathy
Household AreaRecommended Modification to Area
Living areaKeep floors free of clutter35
Remove or secure rugs that may be a tripping hazard35, 36
Ensure good lighting in and outside the home2, 36
Consider use of a nightlight in bedroom or hallway36
KitchenUse pot holders and oven mitts to handle both hot and cold items2, 36
Wear rubber gloves for washing dishes36
Use caution when using sharp objects such as knives
BathroomUse a bathmat or nonslip surface for the bottom of the tub or shower2
Consider use of a bathtub grab bar or bath seat if balance or mobility are issues
Check water temperature with a thermometer or body part with normal sensation before bathing2
Set water heater to below 120 degrees Fahrenheit35
StairsEnsure adequate lighting on stairs36
Use or install handrails for support36
Physical exercise

Exercise has been shown to have positive effects on peripheral neuropathies of varying etiologies.51 Exercise may improve or attenuate symptoms of CIPN through local effects on peripheral nerves by reducing pain and improving physical function.52, 53 Exercise may include both resistance (strength) training as well as aerobic exercise.

A resistance exercise training program can be developed by an exercise professional to address decreases in muscular strength that may occur due to CIPN, cancer treatments, or secondary to inactivity. In patients with CIPN, specific resistance exercises can be prescribed to address weakness in antigravity lower extremity muscles that may be contributing to deficits in gait and function.2 In a Cochrane review examining the effect of resistance exercise on functional ability, resistance exercise was found to moderately improve muscle strength in individuals with peripheral neuropathy.54

Aerobic exercise, such as a cycling on a stationary bike, can be prescribed to improve cardiorespiratory fitness and reduce symptoms of fatigue.55 Aerobic exercise has been shown to preserve neurological function in patients with diabetic neuropathy and more recently, has been proposed as a potential preventative intervention for CIPN.51, 52 In patients who are normally physically active, symptoms associated with CIPN may represent barriers to exercise participation. In these cases, a graded exercise test can be performed to identify symptoms associated with autonomic dysfunction and to rule out any contraindications to exercise. For issues such as sensory loss and impaired balance, guidelines can be provided to reduce risks associated with exercise participation.48, 53

Complementary and alternative therapies

Complementary and alternative medicine therapies include interventions such as meditation, dietary supplements and herbal remedies, massage therapy, and acupuncture. Of the potential complementary and alternative medicine therapies, acupuncture has shown the most promise with reported benefit for symptoms and objective measures in patients with diabetic neuropathy.2 A single case series examining the use of acupuncture in 5 patients with CIPN found that acupuncture treatments provided once per week over a 7- to 12-week period decreased symptoms of pain, numbness, and tingling.56 Moreover, no adverse effects from the treatments occurred, and symptom benefits were sustained in 4 of the 5 patients at 6-month follow-up.56


  1. Top of page
  2. Abstract

Screening and baseline assessment for CIPN should occur prior to the initiation of neurotoxic chemotherapy in the neoadjuvant, adjuvant, and metastatic disease settings. Ongoing surveillance visits provide the clinician the opportunity to assess for emerging signs and symptoms of CIPN. Patients considered at high risk or who require close surveillance may be thus identified. In terms of physical rehabilitation, the baseline visit can be used to provide the patient with education on the need for early identification of CIPN and appropriate management strategies.

Ongoing surveillance following the initiation of a neurotoxic agent is important to monitor for the development and progression of symptoms associated with CIPN (Fig. 1). Patients are generally seen every 2 to 3 weeks by their medical oncologist while receiving chemotherapy and receive a history and physical examination. Comprehensive screening for the presence of CIPN can thus be performed prior to each cycle of chemotherapy. Early identification of CIPN allows for prompt referral to a neuromuscular specialist for formal assessment. In addition, identification of positive (ie, pain) and negative (ie, numbness) symptoms will ensure appropriate referral and timely symptom management (Fig. 2). Ongoing surveillance provides a feedback loop, so the efficacy of prescribed treatments for CIPN can be assessed along with ongoing patient symptoms to ensure each patient's needs are being met.

CIPN is managed best by a multidisciplinary team approach. Communication is key with shared care, because there are differing perspectives as to which provider assumes responsibility for varying aspects of care.57 If the patient is being treated within the same health care system, access to electronic health records facilitates this communication.58 If treatment is in different health care systems, attention to keeping all of the providers informed becomes even more crucial. This is particularly important when a variety of nononcologic providers, such as physical therapists, OTs, neuromuscular specialists (ie, rehabilitation medicine, neurology), and others involved in the management of CIPN are consulted or provide treatment for the patient. Educating the patient about who to see and for what issues is a component of survivorship care and should be included in the survivorship care plan.59 Similar education should be a major component of all other phases of the cancer continuum as well, including in the adjuvant and palliative settings. Patients with residual peripheral neuropathies or other bothersome symptoms should be empowered to request consultations as needed.60

Following curative treatment, a history and physical examination are routinely performed every 3 to 6 months for the first 3 years, every 6 to 12 months for the next 2 years, and annually thereafter.61 Visits may be rotated with the surgeon, medical oncologist, and radiation oncologists so that the patient is seeing each provider approximately once per year. During those visits, patients are monitored for disease recurrence, evaluated for resolution of treatment side effects, and screened for long-term or late complications.62 In addition, CIPN, upper extremity dysfunction, fatigue, overall function, weight gain, and other sequelae of breast cancer treatment should be assessed and treated with specialty referrals for rehabilitation medicine and physical therapy as appropriate. Over time, care shifts more to the primary care provider with fewer visits to the oncology team. Screening for CIPN or its resolution should occur during these visits if the patient has received a neurotoxic agent.


  1. Top of page
  2. Abstract

The prospective surveillance model for physical rehabilitation proposes a systematic approach to facilitate early identification and management of CIPN. The model promotes a patient-centered approach to care from pretreatment through survivorship and palliative care. In this way, the model offers promise in addressing and minimizing both the acute and long-term morbidity associated with CIPN.


  1. Top of page
  2. Abstract

Support for this meeting and supplement were provided by the American Cancer Society through The Longaberger Company®, a direct selling company offering home products including handcrafted baskets made in Ohio, and the Longaberger Horizon of Hope® Campaign, which provided a grant to the American Cancer Society for breast cancer research and education.


The authors made no disclosure.


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  2. Abstract
  • 1
    Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975–2008. National Cancer Institute: Bethesda, MD. Based on November 2010 SEER data submission, posted to the SEER Web site, 2011.
  • 2
    Stubblefield MD, Burstein HJ, Burton AW, et al. NCCN task force report: management of neuropathy in cancer. J Natl Compr Canc Netw. 2009; 7( suppl 5): S1S26.
  • 3
    Cavaletti G, Alberti P, Frigeni B, Piatti M, Susani E. Chemotherapy-induced neuropathy. Curr Treat Options Neurol. 2011; 13: 180190.
  • 4
    Dunlap B, Paice JA. Chemotherapy-induced peripheral neuropathy: a need for standardization in measurement. J Support Oncol. 2006; 4: 398399.
  • 5
    Paice JA. Clinical challenges: chemotherapy-induced peripheral neuropathy. Semin Oncol Nurs. 2009; 25( 2 suppl 1): S8S19.
  • 6
    Stubblefield MD, Custodio CM, Kaufmann P, Dickler MN. Small-fiber neuropathy associated with capecitabine (Xeloda)-induced hand-foot syndrome: a case report. J Clin Neuromuscul Dis. 2006; 7: 128132.
  • 7
    Carlson RW, Allred DC, Anderson BO, et al. Invasive breast cancer. J Natl Compr Canc Netw. 2011; 9: 136222.
  • 8
    Bartsch R, Ziebermayr R, Zielinski CC, Steger GG. Triple-negative breast cancer. Wien Med Wochenschr. 2010; 160: 174181.
  • 9
    Rodler E, Korde L, Gralow J. Current treatment options in triple negative breast cancer. Breast Dis. 2010; 32: 99122.
  • 10
    Argyriou AA, Polychronopoulos P, Iconomou G, Koutras A, Kalofonos HP, Chroni E. Paclitaxel plus carboplatin-induced peripheral neuropathy. A prospective clinical and electrophysiological study in patients suffering from solid malignancies. J Neurol. 2005; 252: 14591464.
  • 11
    Italian General Practitioner Study Group (IGPSG). Chronic symmetric symptomatic polyneuropathy in the elderly: a field screening investigation in two Italian regions. I. Prevalence and general characteristics of the sample. Neurology. 1995; 45: 18321836.
  • 12
    Weimer LH, Podwall D. Medication-induced exacerbation of neuropathy in Charcot Marie Tooth disease. J Neurol Sci. 2006; 242: 4754.
  • 13
    Martino MA, Miller E, Grendys ECJr. The administration of chemotherapy in a patient with Charcot-Marie-Tooth and ovarian cancer. Gynecol Oncol. 2005; 97: 710712.
  • 14
    Jerian SM, Sarosy GA, Link CJJr, Fingert HJ, Reed E, Kohn EC. Incapacitating autonomic neuropathy precipitated by taxol. Gynecol Oncol. 1993; 51: 277280.
  • 15
    Chaudhry V, Rowinsky EK, Sartorius SE, Donehower RC, Cornblath DR. Peripheral neuropathy from taxol and cisplatin combination chemotherapy: clinical and electrophysiological studies. Ann Neurol. 1994; 35: 304311.
  • 16
    Wiernik PH, Schwartz EL, Einzig A, Strauman JJ, Lipton RB, Dutcher JP. Phase I trial of taxol given as a 24-hour infusion every 21 days: responses observed in metastatic melanoma. J Clin Oncol. 1987; 5: 12321239.
  • 17
    Mollman JE, Glover DJ, Hogan WM, Furman RE. Cisplatin neuropathy. Risk factors, prognosis, and protection by WR-2721. Cancer. 1988; 61: 21922195.
  • 18
    Brown T, Havlin K, Weiss G, et al. A phase I trial of taxol given by a 6-hour intravenous infusion. J Clin Oncol. 1991; 9: 12611267.
  • 19
    Sarosy G, Kohn E, Stone DA, et al. Phase I study of taxol and granulocyte colony-stimulating factor in patients with refractory ovarian cancer. J Clin Oncol. 1992; 10: 11651170.
  • 20
    Donehower RC, Rowinsky EK, Grochow LB, Longnecker SM, Ettinger DS. Phase I trial of taxol in patients with advanced cancer. Cancer Treat Rep. 1987; 71: 11711177.
  • 21
    Lee JJ, Swain SM. Peripheral neuropathy induced by microtubule-stabilizing agents. J Clin Oncol. 2006; 24: 16331642.
  • 22
    Carlson K, Ocean AJ. Peripheral neuropathy with microtubule-targeting agents: occurrence and management approach. Clin Breast Cancer. 2011; 11: 7381.
  • 23
    Reyes-Gibby CC, Morrow PK, Buzdar A, Shete S. Chemotherapy-induced peripheral neuropathy as a predictor of neuropathic pain in breast cancer patients previously treated with paclitaxel. J Pain. 2009; 10: 11461150.
  • 24
    Argoff CE, Cole BE, Fishbain DA, Irving GA. Diabetic peripheral neuropathic pain: clinical and quality-of-life issues. Mayo Clin Proc. 2006; 81( 4 suppl): S3S11.
  • 25
    Martyn CN, Hughes RA. Epidemiology of peripheral neuropathy. J Neurol Neurosurg Psychiatry. 1997; 62: 310318.
  • 26
    England JD, Asbury AK. Peripheral neuropathy. Lancet. 2004; 363: 21512161.
  • 27
    Johnsson KE. Lumbar spinal stenosis. A retrospective study of 163 cases in southern Sweden. Acta Orthop Scand. 1995; 66: 403405.
  • 28
    Saperstein DS, Barohn RJ. Peripheral neuropathy due to cobalamin deficiency. Curr Treat Options Neurol. 2002; 4: 197201.
  • 29
    Lopate G, Pestronk A. Inflammatory demyelinating neuropathies. Curr Treat Options Neurol. 2011; 13: 131142.
  • 30
    England JD, Gronseth GS, Franklin G, et al; American Academy of Neurology; American Association of Neuromuscular and Electrodiagnostic Medicine; American Academy of Physical Medicine and Rehabilitation. Evaluation of distal symmetric polyneuropathy: the role of laboratory and genetic testing (an evidence-based review). Muscle Nerve. 2009; 39: 116125.
  • 31
    Cavaletti G, Frigeni B, Lanzani F, et al. Chemotherapy-induced peripheral neurotoxicity assessment: a critical revision of the currently available tools. Eur J Cancer. 2010; 46: 479494.
  • 32
    National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.–06-14_QuickReference_8.5x11.pdf.
  • 33
    Hile ES, Fitzgerald GK, Studenski SA. Persistent mobility disability after neurotoxic chemotherapy. Phys Ther. 2010; 90: 16491657.
  • 34
    Visovsky C, Meyer RR, Roller J, Poppas M. Evaluation and management of peripheral neuropathy in diabetic patients with cancer. Clin J Oncol Nurs. 2008; 12: 243247.
  • 35
    Visovsky C, Collins M, Abbott L, Aschenbrenner J, Hart C. Putting evidence into practice: evidence-based interventions for chemotherapy-induced peripheral neuropathy. Clin J Oncol Nurs. 2007; 11: 901913.
  • 36
    Wickham R. Chemotherapy-induced peripheral neuropathy: a review and implications for oncology nursing practice. Clin J Oncol Nurs. 2007; 11: 361376.
  • 37
    Stubblefield MD. Cancer rehabilitation. Semin Oncol. 2011; 38: 386393.
  • 38
    Bril V, England J, Franklin GM, et al; American Academy of Neurology; American Association of Neuromuscular and Electrodiagnostic Medicine; American Academy of Physical Medicine and Rehabilitation. Evidence-based guideline: Treatment of painful diabetic neuropathy report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. PM R. 2011; 3: 345352.
  • 39
    Jin D, Xu Y, Geng DF, Yan TB. Effect of transcutaneous electrical nerve stimulation on symptomatic diabetic peripheral neuropathy: a meta-analysis of randomized controlled trials. Diabetes Res Clin Pract. 2010; 89: 1015.
  • 40
    Smith TJ, Coyne PJ, Parker GL, Dodson P, Ramakrishnan V. Pilot trial of a patient-specific cutaneous electrostimulation device (MC5-A Calmare®) for chemotherapy-induced peripheral neuropathy. J Pain Symptom Manage. 2010; 40: 883891.
  • 41
    Wampler MA, Topp KS, Miaskowski C, Byl NN, Rugo HS, Hamel K. Quantitative and clinical description of postural instability in women with breast cancer treated with taxane chemotherapy. Arch Phys Med Rehabil. 2007; 88: 10021008.
  • 42
    Bromberg MB, Smith AG. Handbook of Peripheral Neuropathy. Boca Raton, FL: Taylor & Francis Group; 2005.
  • 43
    Tofthagen C, Overcash J, Kip K. Falls in persons with chemotherapy-induced peripheral neuropathy. Support Care Cancer. 2012; 20: 583589.
  • 44
    Chmielewski TL, Hewett TE, Hurd WJ, Snyder-Mackler L. Principles of neuromuscular control for injury prevention and rehabilitation. In: Magee DJ, Zachazewski JE, Quillen WS, ed. Scientific Foundations and Principles of Practice in Musculoskeletal Rehabilitation. Philadelphia, PA: Saunders; 2007: 375387.
  • 45
    Wampler MA, Hamolsky D, Hamel K, Melisko M, Topp KS. Case report: painful peripheral neuropathy following treatment with docetaxel for breast cancer. Clin J Oncol Nurs. 2005; 9: 189193.
  • 46
    Richardson JK, Sandman D, Vela S. A focused exercise regimen improves clinical measures of balance in patients with peripheral neuropathy. Arch Phys Med Rehabil. 2001; 82: 205209.
  • 47
    Richardson JK, Thies SB, DeMott TK, Ashton-Miller JA. Interventions improve gait regularity in patients with peripheral neuropathy while walking on an irregular surface under low light. J Am Geriatr Soc. 2004; 52: 510515.
  • 48
    Visovsky C. Chemotherapy-induced peripheral neuropathy. Cancer Invest. 2003; 21: 439451.
  • 49
    Paice JA. Chronic treatment-related pain in cancer survivors. Pain. 2011; 152( 3 suppl): S84S89.
  • 50
    Lemoignan J, Chasen M, Bhargava R. A retrospective study of the role of an occupational therapist in the cancer nutrition rehabilitation program. Support Care Cancer. 2010; 18: 15891596.
  • 51
    Balducci S, Iacobellis G, Parisi L, et al. Exercise training can modify the natural history of diabetic peripheral neuropathy. J Diabetes Complications. 2006; 20: 216223.
  • 52
    Wonders KY, Reigle BS, Drury DG. Treatment strategies for chemotherapy-induced peripheral neuropathy: potential role of exercise. Oncol Rev. 2010; 4: 117125.
  • 53
    Pfefer MT. Peripheral neuropathy and neuropathic pain. In: Myers J, Nieman D, eds. ACSM's Resources for Clinical Exercise Physiology: Musculoskeletal, Neuromuscular, Neoplastic, Immunologic and Hematologic Conditions, 2nd ed. Baltimore, MD: Wolters Kluwer Lippincott Williams & Wilkins; 2009: 104112.
  • 54
    White CM, Pritchard J, Turner-Stokes L. Exercise for people with peripheral neuropathy. Cochrane Database Syst Rev. 2004;( 4): CD003904.
  • 55
    McNeely ML, Campbell KL, Rowe BH, Klassen TP, Mackey JR, Courneya KS. Effects of exercise on breast cancer patients and survivors: a systematic review and meta-analysis. CMAJ. 2006; 175: 3441.
  • 56
    Wong R, Sagar S. Acupuncture treatment for chemotherapy-induced peripheral neuropathy–a case series. Acupunct Med. 2006; 24: 8791.
  • 57
    Byler JM, Gil KM. Responsibility for long-term care of breast cancer survivors. Breast J. 2011; 17: 216217.
  • 58
    Sada YH, Street RLJr, Singh H, Shada RE, Naik AD. Primary care and communication in shared cancer care: a qualitative study. Am J Manag Care. 2011; 17: 259265.
  • 59
    Smith SL, Singh-Carlson S, Downie L, Payeur N, Wai ES. Survivors of breast cancer: patient perspectives on survivorship care planning. J Cancer Surviv. 2011; 5: 337344.
  • 60
    Davies NJ, Batehup L. Towards a personalised approach to aftercare: a review of cancer follow-up in the UK. J Cancer Surviv. 2011; 5: 142151.
  • 61
    Khatcheressian JL, Wolff AC, Smith TJ, et al. American Society of Clinical Oncology 2006 update of the breast cancer follow-up and management guidelines in the adjuvant setting. J Clin Oncol. 2006; 24: 50915097.
  • 62
    Brennan ME, Houssami N. Overview of long term care of breast cancer survivors. Maturitas. 2011; 69: 106112.
  • 63
    Lahrmann H, Cortelli P, Hilz M, Mathias CJ, Struhal W, Tassinari M. EFNS guidelines on the diagnosis and management of orthostatic hypotension. Eur J Neurol. 2006; 13: 930936.