Assessing Neuropathy
It is essential for health care professionals to perform a baseline neuromuscular
assessment prior to treatment and to repeat assessments throughout treatment to
identify symptoms early. In the clinical trials for Eloxatin, neuropathy was graded
using:
Important Safety
Information Including
Boxed Warning
Anaphylactic-like reactions to ELOXATIN have been reported and may occur within minutes
of ELOXATIN administration. Epinephrine, corticosteroids, and antihistamines have
been employed to alleviate symptoms.
Continue below
- A prelisted module derived from the neurosensory section of the NCI CTC
scale, version 1.0 (for patients receiving adjuvant colon cancer therapy)
- A study-specific neurotoxicity scale, which was different from the NCI
CTC scale (for patients with advanced colorectal cancer)
Refer to tables below for neuropathy assessment guidelines:
Sanofi-aventis Oncology and NCI CTC Classifications of Sensory Neuropathy
| Grade 1 |
Mild paresthesia,
loss of deep tendon reflexes |
Paresthesia or dysesthesia not interfering with function |
Asymptomatic; loss of deep tendon reflexes or paresthesia (including
tingling) but not interfering with function |
| Grade 2 |
Moderate paresthesia, mild or moderate objective sensory loss
|
Paresthesia or dysesthesia interfering with function, but not
activities of daily living (ADL) |
Sensory alteration or paresthesia (including tingling) interfering
with function but not ADL |
| Grade 3 |
Paresthesia that interferes with function or severe objective
sensory loss |
Paresthesia or dysesthesia with pain or function impairment that
interferes with ADL |
Sensory alteration or paresthesia interfering with ADL |
| Grade 4 |
Not applicable |
Persistent paresthesia or dysesthesia that is disabling or life
threatening |
Disabling |
Important Areas of Assessment for Neuropathy
| Dysesthesia and paresthesia |
Have the patient close his/her eyes and compare one side of the
body to the other, assessing the following types of sensation: · Pain
· Light touch · Position · Vibration · Fine discrimination
· Deep tendon reflexes or
muscle stretch reflexes · Achilles reflex
· Quadriceps reflex · Biceps reflex · Triceps reflex |
Do you have problems writing?
Do you have problems picking up small things?
Any numbness or tingling?
Did you have any trouble or odd sensations while breathing after your last
infusion? |
| Decrease in motor function |
Have the patient grip your hand
Have the patient try to resist your movements as you assess specific aspects
of motor function
Test tendon reflexes |
Have you noticed any weakness anywhere in your body?
Do you have more trouble bending?
Can you take objects off high shelves?
Can you grip my hand? |
| Decrease in motor coordination |
Assess gait for evidence of hesitation, stumbling, or holding
onto chairs or walls for support |
Do you have any trouble walking? |
Adapted from Wilkes GM. New therapeutic options in colon cancer: focus on oxaliplatin.
Clin J Oncol Nurs. 2002;6:131-137.
Acute Neuropathy Symptoms Chart
| Dysesthesia, paresthesia, and hypoesthesia of the distal extremities
|
Numbness and tingling of hands, feet, perioral area, or throat
|
Cold—opening freezer, using ice cubes, picking up cold glass,
air-conditioning |
Reversible when body/air warms |
During infusion, patients should avoid sucking on ice chips
Patient should avoid going out into cold and/or wear a scarf, warm mittens,
socks, and footwear
Patients should not breathe deeply when exposed to cold air outside or to
air conditioners
Patients should avoid eating frozen or cold foods and avoid drinking cold
beverages |
| Pharyngolaryngeal dysesthesia |
Dysphagia or dyspnea, without any laryngospasm or bronchospasm
Jaw spasm, abnormal tongue sensation, dysarthria, eye pain, and a feeling
of chest pressure |
Exposure to cold drink or cold air, ice chips |
Resolution on own within minutes to an hour |
Alert patients before treatment that this may occur and not to
panic
Verify that this is not part of a hypersensitivity reaction
Patients should avoid exposure to cold as discussed under Treatment and/or
Prevention for dysesthesia, paresthesia, and hypoesthesia of distal extremities
|
| Muscle cramping |
Hand/forearm, jaw |
Exposure to cold |
Spontaneous |
Patients should avoid exposure to cold as discussed under Treatment
and/or Prevention for dysesthesia, paresthesia, and hypoesthesia of distal
extremities |
Adapted from Wilkes GM. New therapeutic options in colon cancer: focus on oxaliplatin.
Clin J Oncol Nurs. 2002;6:131-137.
Persistent Neuropathy Symptoms Chart
| Sensory neuropathy |
Numbness and tingling, stocking-glove distribution |
Damage to nerve fibers |
Generally reversible if chemotherapy is discontinued or delayed
Improves in most patients in 4 to 6 months |
Fall precautions: Have patients use self-care measures to ensure
safety (eg, handrails, bath mats)
Patients should use gloves or potholders to prevent problems with hot water
or cooking
Inspect skin carefully for burns, abrasions, and cuts |
| Sensory motor neuropathy |
Tripping, stumbling, and weakness in muscles and inability to
perform fine motor functions (eg, buttoning shirt)
Impaired vibration and position sense; sense of spatial position distorted
|
Damage to nerve fibers |
Generally reversible if chemotherapy is discontinued or delayed
Improves in most patients in 4 to 6 months |
Teach patients safety measures
Refer patients to physical or occupational therapist
Have patients do range-of-motion exercises to strengthen muscles |
| Pain |
Burning, tingling |
Progresses from paresthesias |
Generally reversible if chemotherapy is discontinued or held
Improves in most patients in 4 to 6 months |
Identify precipitating factors like cold
Patients should avoid exposure to cold as discussed in the Acute Neuropathy
Symptoms Chart under Treatment and/or Prevention for dysesthesia, paresthesia,
and hypoesthesia of distal extremities |
Adapted from Wilkes GM. New therapeutic options in colon cancer: focus on oxaliplatin.
Clin J Oncol Nurs. 2002;6:131-137.
Dose Modification Recommendations for Acute Sensory and Persistent Sensory Neuropathy1
|
Any grade
|
Grade 1
|
Grade 2
|
Grade 3 or 4
|
|
Prolong ELOXATIN infusion from 2 h to 6 h† (optional)
|
No dose modification recommended
|
consider reducing ELOXATIN dose to 65 mg/m2†
|
Consider discontinuing ELOXATIN tharapy†
|
|
Prolong ELOXATIN infusion from 2 h to 6 h† (optional)
|
No dose modification recommended
|
consider reducing ELOXATIN dose to 65 mg/m2†
|
Consider discontinuing ELOXATIN tharapy†
|
†The 5-FU/LV doses need not be altered. Prolonging the infusion time for ELOXATIN from 2 hours to 6 hours decreases the Cmax by an estimated 32% and may mitigate acute toxicities; infusion times for
5-FU/LV do not need to be changed.
INDICATIONS
Eloxatin® (oxaliplatin injection), used in combination with infusional
5-FU/LV, is
indicated for
- Adjuvant treatment of stage III colon cancer patients who have undergone complete
resection of the primary tumor.
- Treatment of advanced carcinoma of the colon or rectum.
Clinical Safety Considerations
Anaphylactic-like reactions to ELOXATIN have been reported and may occur within
minutes of ELOXATIN administration. Epinephrine, corticosteroids, and antihistamines
have been employed to alleviate symptoms.
- ELOXATIN should not be administered to patients with a history of known allergy
to ELOXATIN or other platinum compounds. Hypersensitivity and anaphylactic/anaphylactoid
reactions to ELOXATIN have been reported and were similar in nature and severity
to those reported with other platinum compounds (ie, rash, urticaria, erythema,
pruritus, and, rarely, bronchospasm and hypotension). These reactions occur within
minutes of administration and should be managed with appropriate supportive therapy.
Drug-related deaths from this reaction have been reported.
- ELOXATIN may cause fetal harm when administered to a pregnant woman. Women of childbearing
potential should be advised not to become pregnant while receiving ELOXATIN. It
is not known whether ELOXATIN or its derivatives are excreted in human milk.
- ELOXATIN has been associated with pulmonary fibrosis (<1% of study patients),
which may be fatal. The combined incidence of cough and dyspnea was 7.4% (<1%
grade 3, no grade 4) in the ELOXATIN plus 5-FU/LV arm compared to 4.5% (no grade
3, 0.1% grade 4) in the 5-FU/LV alone arm in the adjuvant colon cancer study. In
this study, one patient died from eosinophilic pneumonia in the ELOXATIN combination
arm. The combined incidence of cough, dyspnea, and hypoxia was 43% (7% grade 3 and
4) in the ELOXATIN plus 5-FU/LV arm compared to 32% (5% grade 3 and 4) in the irinotecan
plus 5-FU/LV arm in patients with previously untreated colorectal cancer. In case
of unexplained respiratory symptoms, ELOXATIN should be discontinued until pulmonary
investigation excludes interstitial lung disease or pulmonary fibrosis.
- ELOXATIN is associated with two types of primarily peripheral sensory neuropathy:
an acute, reversible type of early onset and a persistent type (>14 days). In
patients with advanced colorectal cancer paresthesias occurred in 77% (all grades)
and 18% (grade 3/4) of previously untreated patients. In previously treated patients,
acute neuropathy occurred in 56% (all grades) and 2% (grade 3/4) of patients; persistent
neuropathy occurred in 48% (all grades) and 6% (grade 3/4) of patients. In patients
with stage II and III colon cancer, paresthesia was seen in 92% (all grades) and
13% (grade 3/4) of patients; 21% (all grades), 0.5% (grade 3/4) had residual paresthesia
at 18-month follow-up.
- Hepatotoxicity, as evidenced in the adjuvant study by increase in transaminases
and alkaline phosphatase was observed more commonly in the ELOXATIN combination
arm. The incidence of increased bilirubin was similar on both arms. Changes noted
on liver biopsies include: peliosis, nodular regenerative hyperplasia or sinusoidal
alterations, perisinusoidal fibrosis and veno-occlusive lesions. Hepatic vascular
disorders should be considered and, if appropriate, investigated in case of abnormal
liver function test results or portal hypertension not explained by liver metastases.
- Monitoring of white blood cell count with differential, hemoglobin, platelet count
and blood chemistries (including ALT, AST, bilirubin and creatinine) is recommended
before each ELOXATIN cycle.
- The safety and effectiveness of ELOXATIN plus 5-FU/LV in patients with renal impairment
have not been evaluated. Since the primary route of platinum elimination is renal,
this combination should be used with caution in patients with preexisting renal
impairment. Clearance of these products may be decreased by coadministration of
potentially nephrotoxic compounds, although this has not been specifically studied.
- The incidence of diarrhea, dehydration, hypokalemia, leukopenia, fatigue and syncope
were higher in patients ≥65 years old.
- Extravasation may result in local pain and inflammation that may be severe and lead
to complications, including necrosis. Injection site reaction, including redness,
swelling and pain, has been reported.
- There have been reports of prolonged prothrombin time and INR occasionally associated
with hemorrhage in patients receiving ELOXATIN plus 5-FU/LV while on anticoagulants.
Patients receiving ELOXATIN plus 5-FU/LV and requiring oral anticoagulants may require
closer monitoring.
- The most common adverse reactions in patients with stage II or III colon cancer
receiving adjuvant therapy were peripheral sensory neuropathy, neutropenia, thrombocytopenia,
anemia, nausea, increase in transaminases and alkaline phosphatase, diarrhea, emesis,
fatigue, and stomatitis. The most common adverse reactions in patients with advanced
colorectal cancer were peripheral sensory neuropathy, fatigue, neutropenia, nausea,
emesis, and diarrhea.
Click
here for additional important information for Eloxatin.
References:
- Haller DG. Safety of oxaliplatin in the treatment of colorectal cancer. Oncology (Williston Park). 2000;14 (suppl 11):15-20.
