Transcript Oxaliplatin-Induced Peripheral Neuropathy`s Effects on Colorectal

Oxaliplatin-Induced Peripheral
Neuropathy’s Effects on Colorectal Cancer
Survivors
Cindy Tofthagen, PhD, ARNP, AOCNP
Assistant Professor
University of South Florida
Postdoctoral Fellow University of
Massachusetts Boston and Dana Farber
Cancer Institute
Background
• over 1,000,000 survivors of colorectal
• 1 in 19 people will develop colorectal cancer during their
lifetime (NCI, 2012)
• the risk of mortality from colorectal cancer has declined
over the last twenty years because of early detection and
new treatment alternatives like oxaliplatin (NCI, 2010).
• Oxaliplatin was approved by the Food and Drug
Administration (FDA) for treatment of metastatic
colorectal cancer in 2002 and approved for first-line
adjuvant treatment of stage III colorectal cancer in 2004
(NCI, 2010).
Background
• Oxaliplatin is highly toxic to the peripheral nervous
system
• Cause chronic neurotoxicity in up to 50% of patients that
can persist for years following completion of
chemotherapy.
• Neurotoxicities may not develop until after completion of
chemotherapy
• Primarily effects sensory neurons
Purpose
To examine severity of neuropathic
symptoms and evaluate relationships
between neuropathic symptoms, healthrelated quality of life, depressive symptoms
and sleep in colorectal survivors who were
treated with oxaliplatin.
Sample & Setting
Men and women with a history of stage III – IV colorectal cancer
treated with oxaliplatin at the Moffitt Cancer Center between 1 and
8 years previously.
Eligibility criteria:
• at least 18 years of age;
• treated with oxaliplatin for stage III – IV colorectal cancer
• have no history of cancer other than colorectal cancer
• no other potentially neuropathy-inducing condition (e.g.,
diabetes)
• no documented or psychiatric or neurologic disorders that
would interfere with study participation
• be able to speak and read standard English
• provide written informed consent.
Procedures
• The Institutional Review Board approved the study
• Patients were identified through the Moffitt Cancer Center
Cancer Registry
• Potentially eligible survivors were contacted by telephone to
confirm eligibility and obtain verbal informed consent
• Survivors who provided verbal consent were then mailed a
study packet and postage paid return envelope
• Approximately 1 week later, those survivors who had not yet
returned the packet were contacted by telephone and
prompted to complete and return the material
• A total of 128 survivors agreed to participate. 111 (94%)
survivors completed and returned the study packet
Instruments
• Chemotherapy Induced Peripheral Neuropathy
Assessment Tool (CIPNAT)
• The Center for Epidemiological Studies-Depression
Scale (CES-D)
•
Insomnia Severity Index (ISI)
• Medical Outcomes Study Short Form- 36 (SF-36)
• Demographic Data Form
Power & Data Analysis
• A priori power analysis indicated that 108 subjects were
needed, at 90% power and 2-sided type I error rate of
0.01, to detect a 10% or more change in R-square
(percentage of variation explained) attributed
independently to level of neuropathic symptoms.
• Correlation coefficients, simple regression and multiple
linear regression analysis were used to examine
relationships between neuropathy and depressive
symptoms, sleep quality, and health-related quality of life
(HRQOL).
Results-Demographics
• 51% male
• 88% Caucasian
• 71% stage 3 colon cancer
• 37% still employed (not retired or disabled)
• Mean of 3 years since oxaliplatin based chemotherapy
Prevalence of Symptoms
Trouble with balance
Arms or legs weak
Muscle or joint aches
Sensitivity to cold
Percentage
Discomfort in feet
Discomfort in hands
Numbness or tingling in feet
Numbness or tingling in hands
0
20
40
60
80
Severity of Symptoms
Mean
Balance Trouble
Muscle Weakness
Muscle/joint aches
Cold Sensitivity
Mean
Discomfort Feet
Discomfort Hands
Numbness/tingling feet
Numbness/tingling hands
0
1
2
3
4
5
6
7
8
9
Symptom Distress
Mean
Balance Trouble
Muscle Weakness
Muscle/joint aches
Cold Sensitivity
Discomfort Feet
Discomfort Hands
Numbness/tingling feet
Numbness/tingling hands
0
1
2
3
4
5
6
7
8
9
Frequency of Symptoms
Mean
Balance Trouble
Muscle Weakness
Muscle/joint aches
Cold Sensitivity
Mean
Discomfort Feet
Discomfort Hands
Numbness/tingling feet
Numbness/tingling hands
0
1
2
3
4
5
6
7
8
9
Correlations Between CIPN, Depressive
Symptoms and Sleep
Variable
Symptom Experience
Symptom Interference
Depressive Symptoms
(CES-D)
.38 (p=.001)
.59 (p<.001)
Sleep Disturbance (ISS)
.35 (p=.004)
.52 (p<.001)
Correlations Between CIPN and QOL
Symptom experience
r
p
Physical functioning
Symptom interference
r
p
-.22
.03
-.55
<.0001
-.36
.0003
-.54
< .0001
-.32
.001
-.59
< .0001
-.36
.0002
-.51
< .0001
-.23
.02
-.51
< .0001
General health
-.003
.98
-.06
.57
Mental health
-.26
.01
-.43
< .0001
-.36
.0002
-.66
< .0001
Role emotional
Role physical
Bodily pain
Vitality
Social functioning
Cluster Analysis
Variable
Instrument
Cluster 1
(n=21) Mean
(SD)
Cluster 2
(n=56)
Mean
(SD)
Cluster 3
(n=17)
Neuro Symptoms
CIPNAT
51.90
(37.73)
63.55
(49.93)
119.65
(58.43)
Depressive symptoms
CES-D
2.48
(3.14)
10.04
(7.07)
23.29
(14.47)
Insomnia
SSI
1.43
(1.54)
8.75
(5.32)
12.47
(6.79)
Age
Demographic data
67.24
(7.52)
55.86
(11.66)
66.18
(9.32)
General Health
(norm based)
SF-36
45.16
(3.11)
43.46
(4.90)
42.61
(4.71)
Physical Functioning
(norm based)
SF-36
56.92
(13.54)
44.47
(11.58)
33.88
(12.98)
Emotional Role Function
(norm based)
SF-36
55.68
(0.00)
51.62
(6.08)
18.04
(15.80)
Discussion
• Colorectal cancer survivors continue to experience
oxaliplatin-induced peripheral neuropathy that adversely
affects emotional and physical well-being and quality of
life for years following treatment
• There is a subset of colorectal cancer survivors who
experience severe neuropathy that affects their ability to
carry out usual activities, and is associated with
increased depressive symptoms, sleep disturbance and
reduced quality of life.
Limitations
• Relatively small sample, cross-sectional design,
convenience sampling
• Lack of racial and ethnic diversity
• While our findings suggest that neuropathy contributes to
depressive symptoms, insomnia, and reduced quality of
life, it is possible that persons with a high degree of
depressive symptoms and/or insomnia are more likely to
report more severe neuropathic symptoms and
neuropathic interference with activities.
Directions for Future Research and
Practice
• Longitudinal studies using larger sample sizes and more diverse
racial and ethnic groups
• Identification of possible modifiable and non-modifiable risk factors
for severe neuropathy that may influence treatment decisions
• Interventions to relieve symptoms and improving physical
performance
• Survivorship programs should include systematic assessment for
neuropathy, provide rehabilitation when needed, and develop support
programs for colorectal cancer survivors which emphasize the
chronic nature of neuropathy, help maximize performance status,and
assist patients in adjusting to and coping with physical and role
limitations.
Acknowledgements
Co-Investigators
• Kristine A. Donovan, PhD, MBA
• Moffitt Cancer Center & Research Institute
• Mary Ann Morgan, PhD, ARNP
• Moffitt Cancer Center & Research Institute
• David Shibata, MD FACS
• Moffitt Cancer Center and Research Institute
Acknowledgements
• Data analysis - Yating Yeh, PhD
Dana-Farber Cancer Institute
• Funding – USF Nursing Faculty in Pilot Research
Projects and the University of Massachusetts Boston Dana Farber /Harvard Cancer Center U54 Cancer
Research Partnership