Transcript Chemotherapy-Induced Peripheral Neuropathy: Why the
Chemotherapy-Induced Peripheral Neuropathy (CIPN): Why the complication?
By: Tiffany Marbach, RN, BSN Alverno College MSN Student Spring 2008 [email protected]
Navigating through this tutorial
• • • To advance to the next slide, click on the To review the previous slide, click on the At any time during the tutorial you wish to review a different section of the tutorial, click on the cell at the top of the screen
Objectives
At the conclusion of this tutorial, the learner should be able to: • Understand how the peripheral nervous system works, & what nerves are affected by neurotoxic agents • Describe the signs and symptoms of Chemotherapy-Induced Peripheral Neuropathy (CIPN) • Identify which types of chemotherapeutic agents contribute/cause CIPN • Understand who is more at risk for developing this complication • Describe how patients can have improved health status and outcomes when educated about how to live with CIPN, as well as how to prevent it • Understand ways to treat CIPN once it has developed
Content of Tutorial
Incidence of CIPN
• Chemotherapy is prolonging life Microsoft Image Clip Art, 2007 • Cancer is becoming a chronic, manageable disease • Many nurses will encounter those affected by this common side effect • Estimated to occur in 20% to nearly 100% of cancer patients undergoing chemotherapy (Smith, Beck, & Cohen, 2008).
What is CIPN?
• Characterized as injury, inflammation, or degeneration of peripheral nerve fibers • Can result in loss of motor and sensory nerve function Microsoft Image Clip Art, 2007 • CIPN can result when certain chemotherapeutic agents are used to treat cancer (Marrs & Newton, 2003) • These agents can be referred to as “neurotoxic”
Why is this important for my practice?
• Encountering more and more survivors with this debilitating condition • Limited research done in this area Microsoft Image Clip Art, 2007
Why is this important for my practice?
Incidence increases with: • Duration of infusion (longer infusion: increased chance) • Drugs given • Previous exposure to neurotoxic drugs • Combination chemotherapies (in which more than one neurotoxic drug is given) • Co-morbidities
Rest and Review!
•
Why is CIPN important for all nurses to learn about?
A. It isn’t; only oncology nurses need to care about it
C. It is the most common chemotherapy side effect
Sorry, but that is NOT why it is important for all nurses to be educated about CIPN.
Please click on the question mark below to go back and try the question again!
CONGRATULATIONS!
That is exactly why all nurses should be educated on CIPN and its effects!
Click on the arrow below to continue with the tutorial.
Pathophysiology of CIPN
Sheffield, Getbodysmart.com, 2008 Used with permission • • • The Peripheral Nervous System (PNS) communicates signals between the central nervous system (CNS, composed of the brain and spinal cord) and the
periphery of the body
(Marrs & Newton, 2003) The peripheral nerves originate from the spinal
cord
The peripheral nervous system is made of three divisions: the sensory
nerves, the motor nerves, and the autonomic nerves
Sensory nerves
•
Sensory nerves are responsible for detecting:
•
Pain
Microsoft Image Clip Art, 2007 •
Touch
•
Temperature
•
Position
•
Vibration
Motor Nerves
•
Motor nerves are responsible for:
•
Voluntary movement
•
Muscle tone
•
Coordination
Microsoft Image Clip Art, 2007
Autonomic nerves
•
Autonomic nerves are responsible for:
•
Intestinal motility
Microsoft Image Clip Art, 2007 •
Blood pressure
•
Involuntary muscle movements
Rest and Review!
• Sensory nerves are responsible for detecting:
A. Blood pressure B. Balance and coordination C. Intestinal Motility
Sorry, but that is NOT the function of the sensory nerves.
Please click on the question mark below to go back and try the question again!
CONGRATULATIONS!
You are correct.
Sensory nerves are responsible for the feelings of temperature, pain, touch, position, and vibration.
Click the arrow below to advance to the next slide.
•
Pathophysiology (continued)
Peripheral nerves are made up of individual neurons, axons,
cell bodies, and dendrites, wrapped in a myelin sheath
Click below for structure of neuron diagram!
• Each nerve fiber (neuron), is made up of single axon • • This axon is surrounded by
Schwann cells
• Schwann cells form myelin
sheath
• Dendrites synapse with other nerves to send a signal across from one nerve to the next (Wickham, 2007) Multiple Sclerosis Resource Centre , 2008 Used with permission
Pathophysiology (continued)
• Cell body: provides nourishment and maintain the nerve fibers • Dendrites: extend from the cell body and receive/carry stimuli to the cell body • Axon: then carries the impulse away from the cell body Microsoft Image Clip Art, 2007
Pathophysiology (continued)
• Peripheral nerve fibers are classified as: myelinated or unmyelinated • They are grouped to their size in diameter (called A, B, and C fibers) • A Fibers: (motor and sensory fibers), are largest in diameter, and are myelinated (allowing for fast impulse conduction)
Pathophysiology (continued)
• B Fibers: (least common fiber), are smaller in diameter, and are less myelinated than A fibers • C Fibers: (some sensory and motor, but autonomic fibers are most common), smallest and slowest conducting of the PNS • Damage to the large fibers (A & B) or small fibers (C), correspond with the signs/symptoms of CIPN (Armstrong, Almadrones & Gilbert, 2005)
Sensory nerves are broken down into:
Large fiber nerves: • Are myelinated • Sense position, motor control, and vibration • Composed of neurofilaments, which act as framework of axon
Sensory nerves are broken down into:
Small fiber nerves: • Are unmyelinated • Include nerves that sense pain and temperature • Speed of impulse transmission depends on if neuron is highly myelinated (fast transmission), lightly myelinated (slower transmission), or unmyelinated (slowest transmission) (Wickham, 2007)
Rest and Review!
•
Highly myelinated nerve cells conduct impulses:
Sorry! Wrong answer. Please try again.
Please click on the question mark below to go back and try the question again!
Nice job!! The highly myelinated nerve cells are very fast conductors!
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Rest and Review!
•
The function of the dendrite portion of the nerve cell is to:
A. Provide the cell with food and nourishment
B. Receive and carry stimuli to the cell body
C. Carry the impulse away from the cell body
OOPS! This is NOT the function of the dendrites… Please click on the question mark below to go back and try the question again!
Excellent answer! The dendrites are responsible for receiving and carrying stimuli to the cell body!
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Pathophysiology (continued)
• Peripheral neuropathy results from damage to the axon,
myelin sheath, or cell body
• Pathogenesis of CIPN is not completely understood • It is known that different sensations arise depending on chemotherapeutic agent administered (Wickham, 2007) Multiple Sclerosis Resource Centre , 2008 Used with permission
Pathophysiology (continued)
• Chemotherapy drugs are believed to first: • Damage sensory axons • Then move on to cause degeneration and dying back of axons and myelin sheaths (Wickham, 2007) National Resource Council Canada, 2005 Used with Permission
Pathophysiology (continued)
• CIPN is usually
symmetrical
Microsoft Image Clip Art, 2007 • Begins in distal end of longest axons • Sometimes known as polyneuropathy: affects many nerves • Toxins (including chemotherapy) are transported along the axon towards the cell body (Wickham, 2007)
The stocking/glove phenomena:
Moves distal to proximal
• CIPN usually progresses from toes to feet to ankles to lower legs (stocking distribution) Microsoft Image Clip Art, 2007 • Upper extremity damage usually comes later • Moves from fingertips to fingers to hands (glove distribution) (Wickham, 2007)
Rest and Review!
•
Nerve cells are damaged by chemotherapy because:
A. They aren’t strong enough to handle the toxicity
B. The chemotherapy causes degeneration and dying back of axons and myelin sheaths
C. The chemotherapy doesn’t affect the nerve cells
No…That’s not how nerve cells are damaged… Please click on the question mark below to go back and try the question again!
You’re RIGHT! That is exactly how nerve cells are damaged! Click the arrow below to advance to the next slide.
Rest and Review!
• In a typical pattern of CIPN, the person experiences neuropathy first in the:
Think again. Where does neuropathy usually show up first in a stocking-glove pattern?
Please click on the question mark below to go back and try the question again!
GREAT job! The neuropathies usually show up first in the lower extremities, and progress later towards the upper extremities.
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Nerve Growth Factor
• • • • • • Axons regenerate if toxic agent removed Damage to cell bodies is not
completely reversible Nerve Growth Factor
(NGF) plays role in neuron repair NGF is usually reduced after neurotoxic chemotherapy Animal studies show if given NGF, some neuropathy and neural structural changes were prevented or reversed Exact mechanism not well understood (Wickham, 2007) Microsoft Image Clip Art, 2007
Inflammation and CIPN: What’s the connection?
• • • • Tissue repair is part of the
inflammatory process
It is an attempt to maintain normal body structure and function Cell regeneration can vary depending on tissue/cell type Three types of cells that are divided according to ability to undergo regeneration:
labile, stable, or permanent cells
(Porth, 2005) Microsoft Image Clip Art, 2007
Nerve cells: Permanent/Fixed Cells
• Labile cells: regenerate and divide throughout life (ex: Epithelial cells found on skin or in the mouth) • Stable Cells: stop dividing when growth ends, but can regenerate when confronted with certain stimuli (ex: liver cells) • Permanent/Fixed cells: cannot undergo mitotic division, and can’t regenerate (ex: nerve and cardiac muscle cells) (Porth, 2005) Microsoft Image Clip Art, 2007
Nerve cells: Permanent/Fixed Cells (continued) • When nerve cell is damaged (for example, from a chemotherapy drug), it can not be
replaced
Microsoft Image Clip Art, 2007 • It is replaced with scar
tissue
• This scar tissue can not function like the destroyed cell can (for example, can’t conduct impulses) (Porth, 2005)
Rest and Review!
•
Peripheral nerve cells are considered:
A. Labile cells B. Stable cells
This is not what nerve cells are classified as… Please click on the question mark below to go back and try the question again!
Right on! Nerve cells are fixed or permanent cells, that can not regenerate!
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Stress and CIPN: What’s the connection?
• • • • CIPN can often lead to pain symptoms This pain is classified as acute or chronic
pain
Acute pain: lasts less than 6 months Chronic pain: lasts 6 months or longer (Porth, 2005) Microsoft Image Clip Art, 2007
• Stress and CIPN: What’s the connection? (continued) CIPN can be considered acute or
chronic
• This depends on length of
treatment, co-morbidities
(pre-existing conditions beside the CIPN), and disease state • This can cause physiologic, psychological, familial, and
economic stress
• Chronic pain can lead to loss of
appetite, sleep disturbance, and depression
(Porth, 2005) Microsoft Image Clip Art, 2007
Stress and CIPN: What’s the connection? (continued)
Two factors determine nature of stress:
Microsoft Image Clip Art, 2007 •
1. Properties of the stressor
•
2. The condition of the person under stress
• Severe, prolonged physical and psychological distress disrupts health with chronic stress (Porth, 2005)
Stress and CIPN: What’s the connection? (continued)
General Adaptation
System (GAS): • Systemic reaction to stressor that causes physical and psychological manifestations • Three stages: Alarm,
Resistance, and Exhaustion
(Porth, 2005) Microsoft Image Clip Art, 2007
Stress and CIPN: What’s the connection? (continued) • 1. Alarm: Stimulation of Sympathetic Nervous System (SNS) • Results in release of catecholamines (such as epinephrine and norepinephrine) and cortisol, which: • Increase heart rate, relaxation of bronchial smooth muscle, decrease insulin release, etc.
• 2. Resistance: Body selects most effective channel of defense
• Stress and CIPN: What’s the connection? (continued) 3. Exhaustion: occurs if stressor is prolonged • Most common with CIPN • Resources of the body’s coping mechanisms are depleted • Wear and tear on systems is appearing • Many ailments, including CIPN, begin to show wear and tear on the person physiologically and
psychologically
(Porth, 2005)
Rest and Review!
•
The stage in of the General Adaptation System (GAS) most active in chronic CIPN is:
Wrong stage of GAS…Try again!
Please click on the question mark below to go back and try the question again!
Correct! The Exhaustion Stage is most active with chronic CIPN.
Click the arrow below to advance to the next slide.
Chemotherapeutic agents that induce peripheral neuropathy • CIPN is a dose-
limiting toxicity
• This means that patients could have chemotherapy dose reduced, or even
held
Microsoft Image Clip Art, 2007 • This interrupts normal chemotherapy cycle which could affect
outcome
• Chemotherapeutic agents that induce peripheral neuropathy: Platinum Compounds Cisplatin & Carboplatin: Affects 57-92% of patients undergoing chemotherapy • Causes axonal swelling and loss • Progress from sensory, to motor, to (rare) autonomic symptoms • Can occur later in treatment course • 66% of patients have full recovery (if developed) • Causes loss of sense of position and vibration • Numbness/tingling (paresthesias) • Some patients can take two years for recovery to occur (Armstrong, Almadrones, & Gilbert, 2005) Microsoft Image Clip Art, 2007
Chemotherapeutic agents that induce peripheral neuropathy (Platinum compounds) Oxaliplatin: • • • • • • • • Alters neuron excitability & interferes with axon conduction Causes sensory neuropathy of large fibers 80% of patients develop 40% of those who develop have resolution of symptoms in 6-8 months Can cause acute neuropathy (30-60 minutes after infusion) Cramps/spasms in hands and feet Aggravated by cold weather Causes sensation of loss of breath, jaw tightness (Armstrong, Almadrones, & Gilbert, 2005) Microsoft Image Clip Art, 2007
Chemotherapeutic agents that induce peripheral neuropathy (Taxanes) • Paclitaxel (Taxol) and Docetaxel
(Taxotere):
Risk depends on dosing & use with other neurotoxic agents • Taxol causes CIPN in 60% of patients • Taxotere causes CIPN in about 49% of patients • Affect small fibers, causes axonal injury, and demyelinization • Altered vibratory sense, loss of deep
tendon reflexes, paresthesias
Microsoft Image Clip Art, 2007 • Causes progressive neurological dysfunction (Armstrong, Almadrones, & Gilbert, 2005)
Chemotherapeutic agents that induce peripheral neuropathy (Vinca Alkaloids)
Vincristine, Etoposide, Vinorelbine & Vinblastine:
• Greatest potential for CIPN is Vincristine: Occurs in about 57% of patients • Degenerates the peripheral nerve fibers • Affects small and large fibers • Causes most commonly: motor and sensory disruption; can cause autonomic effects • Paresthesisas, then progresses to muscle cramping/weakness, constipation, bladder dysfunction, altered heart rate (Marrs & Newton, 2003) Microsoft Image Clip Art, 2007
Chemotherapeutic agents that induce peripheral neuropathy Microsoft Image Clip Art, 2007 • • • • • • • • • Miscellaneous agents used in oncology patients that cause CIPN include: Bortezomib (used for multiple myeloma)
Methotrexate Cytarabine Procarbazine Interferon Thalidomide Corticosteriods 5-FU
Rest and Review!
• Which chemotherapy agent can cause prolonged recovery time with peripheral neuropathies even two years after discontinuation of the drug?
B. 5-FU C. Etoposide D. Methotrexate
This is not correct. Time to try again!!
Please click on the question mark below to go back and try the question again!
Good job! Cisplatin can unfortunately be long-lasting, and take even years to resolve.
Click the arrow below to advance to the next slide.
Rest and Review!
• Which chemotherapy agent can be exacerbated by cold weather and cold objects, causing the patient to have sensation of loss of breath?
A. Carboplatin B. Taxol C. Taxotere
Wrong drug! Go back and look at the question a little closer… Please click on the question mark below to go back and try the question again!
Excellent! Oxaliplatin can cause cold induced neuropathies!
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Signs and Symptoms of CIPN
Microsoft Image Clip Art, 2007 • • Symptoms that patients may experience depend on length of infusion,
dose, co-morbidities,
and the drug being
administered
Symptoms are divided into sensory, motor,
and autonomic
symptoms, correlating with which peripheral nerve is affected
Signs and Symptoms of CIPN
• • Sensory Symptoms include: Microsoft Image Clip Art, 2007 Paresthesia: feeling of warmth, burning, tingling, cold, pinprick sensation, numbness • Hyperesthesia: increased sensitivity to sensory stimulus, not painful, but can cause cramping, usually worse at night • Hypoesthesia: Decreased feeling sensations • Dysesthesia: Abnormal sensation in skin that feels like electric sensation, tingling, prickling of the skin • Hyporeflexia: decreased deep tendon reflexes (Visovsky, Collins, Abbott, Aschenbrenner, & Hart, 2007)
Signs and Symptoms of CIPN
• Diminished/absent vibration sensation • Diminished/absent cutaneous sensation • Diminished/absent sense of feeling object as sharp or dull • Overall loss of sensation • Pain: can be burning, shooting, sharp • Numbness/tingling (American Cancer Society, 2008) Microsoft Image Clip Art, 2007
Signs and Symptoms of CIPN
Motor symptoms include:
Microsoft Image Clip Art, 2007 •
Weakness
•
Gait disturbance
•
Balance disturbance
•
Difficulty with fine motor
skills (for example, writing, buttoning clothing, sewing) (Visovsky et. al., 2007)
Signs and Symptoms of CIPN
Autonomic symptoms include:
•
Constipation
•
Urinary retention
• Sexual dysfunction (erectile dysfunction in men) •
Blood pressure changes
(Visovsky et. al., 2007) Microsoft Image Clip Art, 2007
Rest and Review!
•
Which of the following describes the decreased feeling sensation sometimes experienced with CIPN?
A. Paresthesia B. Hyporeflexia
Try again! There’s a better answer… Please click on the question mark below to go back and try the question again!
Awesome! Hypoesthesia is decreased sensation!
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Rest and Review!
• Which symptom is a result of autonomic nerve damage?
B. Weakness C. Numbness and tingling D. Balance disturbance
Sorry, but this is not a symptom of autonomic nerve damage.
Please click on the question mark below to go back and try the question again!
Nice! Constipation is a common symptom of autonomic nerve damage!
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Assessment of CIPN
Microsoft Image Clip Art, 2007 • • • Baseline neurological assessment is key Allows nurse/staff to recognize changes in peripheral neuropathy once treatment begins Must assess all motor, sensory, and autonomic function not only before start of treatment, but during and after as well (Armstrong, Almadrones, & Gilbert, 2005)
Assessment of CIPN
Problems with current assessment tools:
• Limited because toxicity is determined subjectively by healthcare provider Microsoft Image Clip Art, 2007 • Broad categories used for scoring symptoms • Patients have trouble describing symptoms • Not much assessment beyond presence or absence of CIPN is uniformly performed in most clinic settings (Wampler, Hamolsky, Hame, Melisko, & Topp, 2005)
Assessment of CIPN
Three problems with measuring neuropathy:
•
1. Patient difficulty with describing the uncomfortable sensations, unless they are painful
•
2. CIPN not always been considered a pertinent side effect—usually considered a minor problem that would eventually resolve
• •
3. Easy, simple, and usefully
comprehensive tool has yet to be developed (Smith, Beck, & Cohen, 2008) These problems lead to unanswered questions about how to improve CIPN symptoms Microsoft Image Clip Art, 2007
Assessment of CIPN
Some assessment tools include:
Microsoft Image Clip Art, 2007 • Gait: watch patient ambulate, watch for signs of pain with ambulation or unbalance • Motor: watch for signs of weakness and symmetry • Reflexes in lower extremity: achilles and patellar reflexes • Reflexes in upper extremity: brachioradialis and biceps reflex (Armstrong, Almadrones, & Gilbert, 2005)
Assessment of CIPN
• Sensory: vibration sense and position in great toe to ankle and knee, and finger to wrist and elbow Microsoft Image Clip Art, 2007 • Pinprick sensation from great toe up each leg to point of normal sensation; pinprick from finger up arm to point of normal sensation • Autonomic: assess bowel sounds, orthostatic blood pressures, pulse regularity (Armstrong, Almadrones, & Gilbert, 2005)
Rest and Review!
•
What is a good way to test for motor disturbance in a person affected with CIPN?
A. Vibration sensation testing B. Pinprick sensation testing C. Assess bowel sounds
This is not the best way to test for motor disturbance… Please click on the question mark below to go back and try the question again!
Good job! Testing reflexes is a great way to assess for motor disturbances.
Click the arrow below to advance to the next slide.
Assessment of CIPN
NCI-CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Effects) assesses from Grades 1-4 of Sensory and Motor function: • Grade 1: Asymptomatic • Grade 2: Some sensory alteration or weakness • Grade 3: Interfering with activities of daily living • Grade 4: life threatening and disabling (paralysis) (Wickham, 2007) Microsoft Image Clip Art, 2007
Assessment of CIPN
Microsoft Image Clip Art, 2007 • • ECOG-CTC tool (Eastern Cooperative Oncology Group Common Toxicity Criteria) also is used to assess from Grades 1-4 of Sensory and Motor function
Oxaliplatin-Specific
Scale: assesses Grades 1-4 of specific side effects (Wickham, 2007)
Assessment of CIPN
Total Neuropathy Score: Microsoft Image Clip Art, 2007 • Most comprehensive • Assesses subjective and objective aspects of peripheral nerve function • Assesses presence, characteristics, and location of symptoms, as well as physical findings • Each item scored by doctor or nurse on 0-4 scale (Smith, Beck, & Cohen, 2008)
Assessment of CIPN
• Total Neuropathy Score: Scores summed to obtain total score • Higher scores = higher the degree of neuropathy • Wide scoring range • 0=no problems • 4=severe neuropathy almost causing disability (Smith, Beck, & Cohen, 2008) Microsoft Image Clip Art, 2007
Rest and Review!
•
Which neuropathy scoring tool is considered most effective in regards to comprehensive scoring?
A. NCI-CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Effects)
B. Total Neuropathy Score (TNS)
This is not considered the most comprehensive CIPN screening tool… Please click on the question mark below to go back and try the question again!
YES! The Total Neuropathy Score is considered one of the most effective CIPN screening tools!
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•
Patients at risk for developing CIPN
Some conditions or co morbidities make patients more prone to developing CIPN complication than other patients • The following is a list of other factors that, if present in a patient undergoing chemotherapy with a neurotoxic drug, may put them more at risk for developing CIPN • It’s essential to assess for risk factors to determine who will need close monitoring during treatment!
Microsoft Image Clip Art, 2007
Patients at risk for developing CIPN
Microsoft Image Clip Art, 2007 • • • • • • • • • •
Endocrine diseases
include: Diabetes mellitus (already can causes small fiber injury) Hypothyroidism
Infectious diseases
include: HIV/AIDS Lyme disease Herpes zoster
Hereditary diseases
include: Charcot-Marie-Tooth syndrome (causes large fiber injury) Freidreich’s ataxia (Wickham, 2007)
Patients at risk for developing CIPN
• • • • • • •
Nutritional diseases
include: Alcoholism Vitamin B12 deficiency (causes large fiber injury) Thiamine deficiency Vitamin E deficiency Folate deficiency Crohn’s disease (Wickham, 2007) Microsoft Image Clip Art, 2007
Patients at risk for developing CIPN
Microsoft Image Clip Art, 2007 • • • • • • • • • • • • • • •
Connective tissue diseases:
Rheumatoid arthritis Lupus
Metal neuropathy:
Mercury Gold Thallium
Other:
Amyloidosis Atherosclerotic heart disease Sarcoidosis Biliary cirrhosis Uremia Vasculitis Ischemic lesions (Wickham, 2007)
Patients at risk for developing CIPN
• Medications including: Microsoft Image Clip Art, 2007 • • • • • • • • • • Colchicine Isoniazid Hydralazine Metronidazole Lithium Phenytoin Cimetadine Amiodarone Pyridoxine Amitriptyline (Wickham, 2007)
Patients at risk for developing CIPN
• Toxic neuropathy: • • • • • Acrylamide Carbon disulfide Ethylene oxide Carbon monoxide Glue sniffing (Wickham, 2007) Microsoft Image Clip Art, 2007
Rest and Review!
•
Which vitamin deficiency may contribute to tendency to develop CIPN?
A. Vitamin C B. Vitamin D C. Vitamin K
Not the correct Vitamin deficiency… Please click on the question mark below to go back and try the question again!
Yes! Vitamin E deficiency is thought to play a role in development of CIPN!
Click the arrow below to advance to the next slide.
Rest and Review!
•
Which disease or condition may predispose a patient to developing CIPN?
A. Atherosclerotic heart disease
B. Pregnancy C. Eczema D. Depression
Try again…This condition does not predispose someone to developing CIPN… Please click on the question mark below to go back and try the question again!
CORRECT! Atherosclerosis can predispose a person to developing CIPN!
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Genetics and CIPN
• Observations strongly suggest
correlation between genetics and development of CIPN and pain
• Not many studies done on development of neuropathic pain or peripheral neuropathies in cancer patients • No common genetic markers have been satisfactorily identified (Ossipov & Porreca, 2005) Microsoft Image Clip Art, 2007
Genetics and CIPN
• One study suggests there may be genetic component in patients receiving Taxol for cancer • ABCB1 is a protein involved in Taxol elimination and distribution • Is expressed in the blood-brain barrier • It is not detected in peripheral nerve cells Microsoft Image Clip Art, 2007 • However, the cells that make up blood-nerve barrier express ABCB1 (Sissung, Mross, Steinberg, Behringer, Figg, Sparreboom, & Mielke, 2006)
Genetics and CIPN
• ABCB1 may protect peripheral nervous tissue • It does this by taking toxic
substances away from the
nervous system, and puts it back into systemic circulation • Based on expression, it was hypothesized that patients with low-expressed ABCB1 gene variations would be more likely to experience CIPN (Sissung et. al., 2006) Microsoft Image Clip Art, 2007
Genetics and CIPN
• None of the patients carrying the “wild” allele for ABCB1 gene developed CIPN • Patients carrying different variations of the gene did tend to have increased risk of developing CIPN • Data suggests possible genetic predisposition to CIPN with regulation of the ABCB1 gene (Sissung et. al., 2006) Microsoft Image Clip Art, 2007
Genetics and CIPN
• More research needs to be done in the area of genetics and CIPN—there could be a link!
Limitations of the study
include: • • Small sample size Taxol-based therapy only was tested Microsoft Image Clip Art, 2007
Rest and Review!
•
With more research in the area of genetics, there is a possibility that genetics may play a role in the development of CIPN.
Try one more time!
Please click on the question mark below to go back and try the question again!
Right answer! With more research, they may find a genetic component to the development of CIPN!
Click the arrow below to advance to the next slide.
•
Prevention of CIPN
No treatment available to clinically reverse CIPN!
• As health care professionals, it is important to educate patients on ways to prevent CIPN
Ways to prevent include:
• • Treating and recognizing pre existing conditions that put patients at risk Frequent assessment during therapy (Armstrong, Almadrones, & Gilbert, 2005) Microsoft Image Clip Art, 2007
•
Pharmacologic treatment of CIPN
Amifostine: Chemoprotectant • Detoxifies chemotherapy drugs • Facilitates DNA repair of cells • Does not interfere with chemotherapy effectiveness • In lab animals, shows sparing of nerve fibers • In some human trials, it seems ineffective in preventing or reducing Taxol-induced PN • Needs more research with other chemotherapy drugs (Visovsky et. al., 2007) Microsoft Image Clip Art, 2007
Pharmacologic treatment of CIPN
• Vitamin E: Protects against cell damage such as numbness, tingling, burning, and pain in periphery caused by Cisplatin and other chemotherapy drugs • Studies show those who received Vitamin E supplementation during and after chemotherapy reported less CIPN • Possibly a relationship between Cisplatin neurotoxicity and Vitamin E deficiency (Visovsky et. al., 2007) Microsoft Image Clip Art, 2007
Pharmacologic treatment of CIPN
Calcium/Magnesium infusions: • Oxalate, found in Oxaliplatin, binds to Calcium and Magnesium • This may deplete these essential elements and be responsible for the neurotoxicity of Oxaliplatin • Patients received 1 gram of both Magnesium and Calcium before and after Oxaliplatin infusion • 65% in infusion group had no CIPN, compared to 37% in control (Visovsky et. al., 2007) Microsoft Image Clip Art, 2007
Pharmacologic treatment of CIPN
Microsoft Image Clip Art, 2007 Tricyclic antidepressants: • Analgesic effect in treatment of CIPN • Been studied as a relief of paresthesias, including burning, shooting, or tingling pain Anticonvulsants: • Protect against Oxaliplatin-induced CIPN • Patients who were treated with Carbamazepine had no CIPN compared to control group (Visovsky et. al., 2007)
Pharmacologic treatment of CIPN
Microsoft Image Clip Art, 2007 Acetyl-L-carnitine: • • Tested in presence of preexisting Taxol or Cisplatin-induced CIPN Very small studies have been performed, but look promising (Visovsky et. al., 2007) • • Xaliproden: Oral neuroprotecive drug, NGF analog Incidence of Grade 3-4 CIPN was 39% less in patients who received drug versus placebo (Wickham, 2007)
Pharmacologic treatment of CIPN
Glutamine: • Amino acid, may have neuroprotecive properties • Upregulates NGF • In studies, those who take it for Taxol- preventive CIPN showed less weakness, loss of vibratory sensation, and toe numbness versus control group (Visovsky et. al., 2007) Microsoft Image Clip Art, 2007
Pharmacologic treatment of CIPN
Glutathione: Microsoft Image Clip Art, 2007 • • • May hamper initial accumulation of platinum agents in peripheral nerve cells Incidence of neuropathy was greater in placebo than control group In some studies, incidences of no CIPN were reported with IV infusion (Visovsky et. al., 2007) Opioids: • • Useful for painful CIPN Doses can be titrated to effective range for CIPN and pain (Wickham, 2007)
Pharmacologic treatment of CIPN
Alpha Lipoic acid: Microsoft Image Clip Art, 2007 • • • Been studied in use with diabetic polyneuropathy No studies done yet with oncology population Significantly improved pain, burning, paresthesias, and numbness in diabetic patients Capsaicin ointment: • • Used in diabetic patients Decrease in neuropathies in diabetic patients studied (Visovsky et. al., 2007)
Rest and Review!
• What class of drugs can be used to treat pain associated with CIPN?
B. Beta blockers C. ACE inhibitors D. Vitamins
These do not treat pain associated with CIPN!
Please click on the question mark below to go back and try the question again!
Great! Tricyclic antidepressants show some analgesic pain relief in patients with CIPN!
Click the arrow below to advance to the next slide.
Rest and Review!
•
Which amino acid may help prevent CIPN, especially in patients treated with Taxol?
Wrong amino acid. Try again!
Please click on the question mark below to go back and try the question again!
Right answer!! Glutamine shows some neuroprotective properties in patients with CIPN!
Click the arrow below to advance to the next slide.
Nonpharmacologic treatment of CIPN
Acupuncture: • • • Shown gait improvement Has shown improvement in sensation and balance Patients taking pain medication for CIPN ended up decreasing doses • • Assistive devices: Canes or orthotics Help prevent injury related to CIPN pain and sensory/motor changes (Visovsky et. al., 2007) Microsoft Image Clip Art, 2007
Nonpharmacologic treatment of CIPN
Activity and exercise: Microsoft Image Clip Art, 2007 • • Strengthening programs may be effective in reversing muscle strength lost to CIPN In severe CIPN, may need Occupational and/or Physical Therapy involvement • •
Pulsed Infrared Light Therapy (PILT):
Delivers infrared light to improve foot perfusion Not studied in oncology population, but did show improvement in sensation in diabetic neuropathy (Visovsky et. al., 2007)
Nonpharmacologic treatment of CIPN
• •
Transcutaneous nerve
stimulation (TENS): Blocks conduction of nerve signal to brain through electrical impulses Improvement in numbness, pain, prickling sensation • • Relaxation breathing: Includes deep-breathing exercise, yoga, meditation, and guided imagery Improves stress and pain related to CIPN, and helps with improvement in mood (Marrs & Newton, 2003) Microsoft Image Clip Art, 2007
Rest and Review!
•
Which of the activity can you suggest to patients as a nonpharmacologic way to control CIPN symptoms?
B. Heavy lifting C. Pursed-lip breathing D. Running 4 miles
This IS NOT an appropriate nonpharmacologic intervention… Please click on the question mark below to go back and try the question again!
Good job!! Yoga is a great thing to teach patients to help control neuropathy and pain.
Click the arrow below to advance to the next slide.
Patient Teaching
• Teach signs/symptoms early on in treatment Microsoft Image Clip Art, 2007 • Instruct patients to report symptoms as soon as they emerge • Teach strategies for personal safety (for example, relying on visual input to compensate loss of lower-extremity sensation, remove throw rugs, use bath mats, etc) (ONS, 2006)
Patient Teaching
• • • • Use good foot/hand care Teach of risk for thermal injury due to loss of extremity sensation by: • Lowering water temperature in home water heater to avoid burns • • Use bath thermometer • Teach strategies to prevent autonomic dysfunction including postural hypotension, constipation, & urinary retention by: Dangling legs before arising Consuming high fiber diet Implementing stool softener use if needed • Inspect hands/feet daily for sores/blisters • Adequate fluid intake (ONS, 2006)
Case Study
You are a nurse working in a busy oncology outpatient clinic. You are starting a 50 year-old African American patient named “Joan” on chemotherapy for Stage III breast cancer. She is in your chemotherapy chair for the first time today for teaching and her first chemotherapy dose…
The oncologist is ordering four cycles of doxorubicin (Adriamycin), along with cyclophosphamide (Cytoxan). This will be given every three weeks for a total of 12 weeks.
She will then receive four cycles of paclitaxel (Taxol) therapy…
You decide to first review Joan’s history with her. You find out she has quite a few co-morbidities in addition to her breast cancer, including insulin dependent diabetes mellitus for 10 years, a history of alcohol abuse, depression, and hypothyroidism…
Which of the co-morbidities listed below does NOT make her more susceptible to developing CIPN?
OOPS! Try again, there is a better answer as to which disease will not predispose this patient to developing CIPN… Please click on the question mark below to go back and try the question again!
Great job!
Depression is not a co-morbidity associated with increased risk of developing CIPN. However, you should continue to watch depressive symptoms, as they may progress with a cancer diagnosis and during treatment… Click the arrow below to advance to the next slide.
Being the excellent nurse you are, you assess her baseline neurological functioning… She does not have any problems picking up objects off the floor, buttoning a shirt, or any feeling of numbness or tingling in her extremities….
What else should you assess before proceeding with chemotherapy?
Her baseline understanding of CIPN B.
There may be more answers to the question… Please click on the question mark below to go back and try the question again!
Excellent job!! All of the listed statements are correct, and all of those factors need to be assessed prior to chemotherapy initiation!
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Joan does very well with her four cycles of Adriamycin and Cytoxan. She has now received her first dose of Taxol… She comes to the clinic and reports that she is feeling well and has no new concerns…
Joan states that she has no problems with her fingers/toes and has no neuropathies. Which of the following statements should make you as the nurse assessing CIPN, investigate more?
“I feel like I am forgetting things like names and faces”
“I have been dropping things around the house a lot more lately”
“I have been eating and drinking well” “I have had no fevers or chills”
This is not a statement that warrants further investigation when assessing for CIPN, but should be pursued further if necessary… Please click on the question mark below to go back and try the question again!
Way to go!!
You’re correct—if the patient reports she is dropping objects around the house for no apparent reason, she may be showing signs of CIPN.
Click the arrow below to advance to the next slide.
Since Joan reports she is dropping things around the house, and after further investigation, admits her fingers and toes have become numb and sometimes painful, you decide to talk with the MD, who prescribes her to take Glutamine 10 grams every day for the first 5 days after chemotherapy, to help with her neuropathy…
The patient agrees to start Glutamine, and does take it as directed.
She returns to clinic after her third cycle of Taxol, and reports that her hands and feet have now become painful and she is having difficulty walking… She is prescribed an analgesic for her pain, which is only minimally helpful…
What other strategies and nonpharmacologic ways can you describe for Joan to help her with her neuropathies and pain?
Yoga Light exercise Training for a marathon Relaxation breathing
There may be more answers to the question… Please click on the question mark below to go back and try the question again!
Great answer!!
Yoga, relaxation breathing, and light exercise are all great ways to try to combat neuropathies and pain!
Click the arrow below to advance to the next slide.
Despite your best efforts, as well as the MD’s recommendations, the patient’s pain improves only slightly. She starts to have balance problems and describes being “very uncomfortable…”
What can you, as the nurse, initiate next?
Talk to the MD about a referral to Physical and Occupational therapy
Wait and see if the pain improves once her chemotherapy is completed C.
Nothing—if the MD doesn’t think it’s a problem, then there shouldn’t be a concern None of the above
Not true! There is ALWAYS something you can do to try and help a patient… Please click on the question mark below to go back and try the question again!
You’re right!!
Often times when CIPN has progressed, physical therapy and/or occupational therapy can help restore some normal functioning!
Click the arrow below to advance to the next slide.
With a referral to physical and occupational therapy, and a dose reduction in her final Taxol treatment, the patient reports better symptom management. She is also using a cane as needed to help her balance…
What should you, as the nurse involved in her case, do now?
Nothing—she is improving and finished with chemotherapy, so she is no longer your patient B.
Call her on the phone every once in a while to check in with her
Continue to make appointments so assessment of CIPN can be monitored
Can’t you do a little more to help this patient?
Please click on the question mark below to go back and try the question again!
Great answer! By making future appointments with the patient, you can continue to assess her progress with neuropathy… Click the arrow below to advance to the next slide.
For more information
• • • • • • Here are a list of websites that focus on peripheral neuropathy: CancerSymptoms.org: “Peripheral Neuropathy” www.cancersymptoms.org/peripheralneuropathy/index.sht
ml National Institute of Neurological Disorders and Stroke: “Peripheral Neuropathy Fact Sheet” www.ninds.nih.gov/disorders/peripheralneuropathy/detail_ peripheralneuropathy.htm
Cancer Supportive Care Programs: “Chemotherapy Induced Peripheral Neuropathy Fact Sheet” www.cancersupportivecare.com/nervepain.php
National Coalition for Cancer Survivorship: “Neuropathy” www.canceradvocacy.org/resources/essential/effects/neur opathy.aspx
(Wickham, 2007)
References:
• • • • • • • • American Cancer Society. (2008, Winter). Side effects of therapy. Cure: Cancer Updates, Research, & Education , 58-62.
Armstrong, T., Almadrones, L., & Gilbert, M. R. (2005). Chemotherapy Induced peripheral neuropathy. Oncology Nursing Forum, 32 (2), 305-311.
Marrs, J., & Newton, S. (2003). Updating your peripheral neuropathy "know-how". Clinical Journal of Oncology Nursing, 7 treat chemotherapy-induced peripheral neuropathy. novel treatment strategies for neuropathic pain. (3), 299-303.
Microsoft Office clip are available from: http://office.microsoft.com/en us/clipart/default.aspx
Multiple Sclerosis Resource Centre. (2008). Structure of a typical neuron & Damaged Neuron [Online images]. Retrieved February 27, 2008 from the Multiple Sclerosis Resource Centre website at: http://www.msrc.co.uk/images/gallery/nerve1.jpg
Oestreicher, P. (2007). Five minute inservice: Put evidence into practice to ONS Connect Oncology Nursing Society (ONS). (2006). Peripheral neuropathy: What interventions are used to prevent or reduce the effects of peripheral neuropathy for people with cancer? PEP Card. Pittsburgh, PA.
Ossipov, M. H., & Porreca, F. (2005). Challenges in the development of The Journal of the American Society for Experimental Neurotherapeutics, 2 , 24-25.
(4), 650-661.
• • • • • • • • •
References (continued):
Porth, C. M. (2005). Pathophysiology concepts of altered health states Philadelphia: Lippincott.
(7th ed.). Sheffield, S. (2008). Getbodysmart.com (2008). The nervous system: Anatomy and Physiology [Online image]. Retrieved March 12,2008 from http://getbodysmart.com/ap/nervoussystem/menu/menu.html
. Smith, E. M., Beck, S. L., & Cohen, J. (2008). The total neuropathy score: A tool for measuring chemotherapy-induced peripheral neuropathy. 96-101.
Sissung, T. M., Mross, K., Steinberg, S. M., Behringer, D., Figg, W. D., Sparreboom, A., et al. (2006). Association of ABCB1 genotypes with paclitaxel-mediated peripheral neuropathy and neutropenia. Turner, H. (2005). Microscopic image of a nerve cell [online image]. Retrieved February 27, 2008 from the National Research Council Canada website at: http://www.nrc cnrc.gc.ca/images/education/pl_nerve.jpg
Visovsky, C., Collins, M., Abbott, L., Aschenbrenner, J., & Hart, C. (2007). Putting evidence into practice: Evidence-based interventions for chemotherapy-induced peripheral neuropathy. 359.
European Journal Cancer, 42 (17), 2893-2896.
Clinical Journal of Oncology Nursing, 11 peripheral neuropathy. Oncology Nursing Forum, 35 (6), 901-913.
(1), Visovsky, C., & Daly, B. J. (2004). Clinical evaluation and patterns of chemotherapy-induced Journal of the American Academy of Nurse Practitioners, 16 Painful peripheral neuropathy following treatment with docetaxel for breast cancer. (8), 353 Wampler, M. A., Hamolsky, D., Hamel, K., Melisko, M., & Topp, K. S. (2005). Case report: Clinical Journal of Oncology Nursing, 9 (2), 189-193.
Wickham, R. (2007). Chemotherapy-induced peripheral neuropathy: A review and implications for oncology nursing practice. 376.
Clinical Journal of Oncology Nursing, 11 (3), 361-
Questions, Comments, or Suggestions?
• • Please feel free to email me with any questions, ideas, suggestions, or comments regarding this tutorial. I welcome the correspondence!
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