3. Peripheral Neuropathy (PN)
Damage to the peripheral nervous system caused by injury,
inflammation, or degeneration of peripheral nerve fibers which can
affect QOL, compromise optimal treatments
Incidence of PN is increasing
More neurotoxic drugs have been developed
Patients are living longer, multiple treatment regimens
Multifactoral
Older age, chemotherapy dose/duration
Prior cisplatin or vinca alkaloids
Co-administration with other neurotoxic agents
Pre-existing conditions such as DM, HIV positive, female gender, Vit
B12 deficiency/B6 toxicity
Tariman et al, 2008; Wickham, 2007; Thalomid® prescribing information, 2007; Velcade® prescribing information,2009.
5. Peripheral Neuropathy (PN):
General Concepts
PN can lead to structural damage in the
peripheral nerves of the central nervous
system
Sensory component of neuropathy has 2
primary types
Small fiber: Pin-prick, pain and
temperature
Large fiber: Vibration and proprioception
CIPN = chemotherapy-induced peripheral neuropathy.
Armstrong et al, 2005. Ropper & Gorson, 1998
6. PN: Signs and Symptoms
Tariman et al, 2008; Wickham, 2007.
Mild Moderate Severe
Numbness Prickling Pain
Hyper-, hypo-, or
dys-esthesias
Sensitivity to
touch
Muscle wasting
Muscle weakness Paralysis
Organ failure
Hypotension, dizziness
STOP
Symptoms:
Diminished or absent:
• proprioception
• vibratory sensation
• touch sensation
• sense of sharp/dull discrimination
7. Agent Incidence of PN
Cisplatin •Incidence of PN is approximately 50%
•PN when cumulative doses exceed 300 mg/m2 (or rarely
at lower doses/various administration schedules)
• Occurs in up to 90% of cumulative doses > 500 mg/m2
Vincristine •Cumulative dose of 10 mg causes stocking-glove sensory
loss, areflexia, pain; can cause autonomic neuropathy; 1/3
report continued symptoms post-treatment
Prediction: Chemotherapy Agents
Associated with PN
VAD= Vincristine, adriamycin, dexamethasone; DVD = Dexamethasone, vincristine, dexamethasone
Cavaletti et al, 1992; LoMonaco et al, 1992; Mollman et al, 1988; Krarup-Hansen et al, 2007; Grothey, 2003; Quasthoff et al, 2002;
de Gramont et al, 2000; Land et al, 2007; Pietrangeli et al, 2006; Dougherty et al, 2007; Verstappen et al, 2005; Chaudhry et al, 2003;
Seidman et al, 2004; Winer et al, 2004.
8. Prediction: Chemotherapy Agents
Associated with PN
Agent Incidence
Bortezomib •Grade 1/2 occur in ~ 75% with recurrent
disease; 33% with newly diagnosed
•In a Phase II trial of bortezomib in relapsed
MM, 81% previously treated had PN
(regardless of prior therapy)
Thalidomide •Grade 1/2 PN occurs in 80% pts previously
treated for MM
•Grade 3/4 PN can occur in ~ 4% when
combined with dexamethasone; all grades
53.9% when combined with dexamethasone
MM= Multiple Myeloma: Badros et al, 2007; Argyriou, Iconomou, et al, 2008; Jagannath et al, 2005; Gupta et al, 2006; Thomas et al,
2007; Buzdar, 2008; Argyriou, Koltzenburgh, et al, 2008; Chan et al, 1999; Thalomid® prescribing information, 2007.
9. Diagnosis of PN
The diagnosis of PN is not straightforward
PN “grading” can give us an idea as to
severity
Available grading scales have many
limitations (wide variations in ones’ opinion)
Grade 1 Grade 2 Grade 3 Grade 4
Peripheral
Sensory
Neuropathy**
Asymptomatic
loss of DTRs,
paresthesia
Moderate
symptoms;
limiting
instrumental ADL
Severe
symptoms;
limiting self
care ADL
Life-threatening;
urgent
intervention
indicated
NCI Common Terminology Criteria for Adverse Events v4.0 (CT-CAE): Publish Date: May 28, 2009
PN = peripheral neuropathy.
10. Diagnostic Studies
Serum:
HIV, herpes, Vitamin B12 deficiency,B6
toxicity, CBC diff
Radiology
X-ray, CT, MRI
Neurodiagnostic studies
EMG
NCV :Nerve conduction velocity
Epidermal skin biopsy
CT = computed tomography; MRI = magnetic resonance imaging; EMG = electromyography;
NCV = nerve conduction velocity; QST = quantitative sensory test.
Galer et al, 2000; Kovacs et al, 2006.
These are only a few
of the available tests
and procedures to
diagnose PN
Subjective and
objective
assessments are
important to correctly
diagnose PN
11. Assessment of PN
Diagnosis is often subjective
Patients will often volunteer change in sensation, gait or
other signs of PN when asked
Evaluate sensory, motor and autonomic symptoms
Subjective assessment: Symptoms related to PN
Pain, numbness, burning, tingling, paresthesias, and
autonomic signs
Objective assessment: Touch, vibration, gait and balance,
proprioception, reflexes, muscle strength
Perception of sharp/dull are recommended as an adjunct to
the subjective symptom assessment
Difficulty with fine motor skills: opening jars,buttoning
Shy et al, 2003; Cavaletti et al, 2003; Dyck et al., 2000.
12. Assessment of PN
1. Proprioception (rhomberg)
Test of motion and orientation
2. Sharp/Dull Perception
Pin Prick Test
3. Temperature sensation
Tuning fork, test tubes with water
4. Vibratory sense
128 Hz tuning fork with the heel of the hand
5. Gait, muscle strength, reflexes
Shy et al, 2003; Cavaletti et al, 2003; Dyck et al., 2000.
Currently, no guidelines exist for the assessment or management of
chemotherapy-induced peripheral neuropathy .
13. FACT-GOG/ntx
Neuropathy Assessment Tool
Not at All
A Little
Bit
Somewhat Quite a Bit
Very
Much
I have numbness or tingling in my hands 0 1 2 3 4
I have numbness or tingling in my feet 0 1 2 3 4
I feel discomfort in my hands 0 1 2 3 4
I feel discomfort in my feet 0 1 2 3 4
I have joint pain or muscle cramps 0 1 2 3 4
I feel weak all over 0 1 2 3 4
I have trouble hearing 0 1 2 3 4
I get a ringing or buzzing in myears 0 1 2 3 4
I have trouble buttoning buttons 0 1 2 3 4
I have trouble feeling the shape ofsmall
objects when they are in my hand
0 1 2 3 4
I have trouble walking 0 1 2 3 4
Cella et al, 2003.
14. PN: Prevention and
Management Strategies
No prevention exists
Regular monitoring at each treatment visit
Neurotoxicity BEFORE EACH DOSE
Treatment dose and schedule modifications-
most effective
Pharmacologic and nonpharmacologic
interventions
Patient education
Dose reductions of bortezomib, thalidomide
and other chemotherapy agents can prevent
moderate to severe PN which impairs QOL
Tariman et al, 2008; Wickham, 2007; Thalomid® prescribing information, 2007; Velcade® prescribing information,2007.
15. Issues Surrounding Neurotoxicity
Trials
Few well-conducted trials in literature
Sample sizes too small, underpowered
Non-randomized, no placebo control
Mix of chemotherapy agents allowed
Mix of palliative and adjuvant setting
Limited success in neurotoxicity prevention and treatment trials
May be due to poor trial design, lack of nurse researchers
Costs
17. Palliation: Non-Pharmacologic
Acupuncture – limited data on PN
No data in PN on
Physical activity/exercise
TENS (transcutaneous external nerve
stimulation)
Meditation/bio-feedback
Pulsed infrared light therapy or
anodyne therapy
Armstrong et al, 2005; Arnall et al, 2006; Grothey, 2008.
18. Palliation:
Practical Management of PN
Patient education
Notify clinician if signs and symptoms worsen
Home safety with decreased sensation in extremities
Caution patient on operating machinery
Family members to assess hot/cold if the patient is unable
Pharmaceuticals
Drug schedule and dose modifications of anti-myeloma therapy
Over-the-counter drugs
Vitamins/minerals/supplements – replace B vitamins, mag, ca++,
glutamine
Amino acids (Glutamine, acetyl-L-carnitine, alpha lipoic acid)
Capsaicin, cocoa butter or emollients
Prescription drugs- No FDA-approved drug for PN
Unsure benefit of gabapentin, amitriptyline, sertraline, lidocaine
patch
Tariman et al, 2008; Wickham, 2007; Visovsky et al, 2007; Armstrong et al, 2005.
19. Additional Considerations for Patients at
Risk for PN
Accurate baseline and ongoing assessment
with a focused physical assessment of
symptoms
Patient education
Safety!!!
Symptom reporting
Self-care strategies (exercise)
Discuss adjunct therapies with healthcare
provider and monitor effectiveness
Referral for assistive devices to maintain ADL
and prevent injuries from falls
Wickham, 2007; Visovsky et al, 2007.
20. Key Takeaways: Patient
Assessment
There are no gold-standard, evidence-based
recommendations for the assessment of PN
Nurses are critical in early recognition and prompt
intervention when symptoms of PN develop
Baseline assessment of PN prior to the initiation of
anti-MM therapy
Identify individuals at risk for severe PN
Educate if treatment must be given (Comorbid
illness, prior treatments)
Ongoing assessment of PN is recommended
Hausheer et al, 2006; Wickham, 2007.
