Case St dies
u
in the Management
Management of
of Veno
Veno s
u
Thromboembolic Events and Peripheral
Neuropathy in
in Multiple
Multiple Myeloma
Myeloma
Accredited by Medical Education Resources
Supported by
by The International Myeloma
Myeloma Foundation
Grant Funding provided by
Celgene Corp
gporation and Millennium: The Takeda Oncology
gy Company
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·
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·
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)plete the evaluation form, 4) mail, e-mail or fax the
completed forms to Medical Education Resources at
· Mail: Medical Education Resources
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Li l
tt eton, CO
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·
A statement of credit will be issued only upon receipt of a completed
activity form and a completed posttest with a score of 70% or better.
Statements of credit will be mailed within 6 weeks of the activity.
Beth Faiman MSN, APRN, BC, AOCN®
Pre-Doctoral Research Fellow,
Francis Payne Bolton School of Nursing at Case Western Reserve
Nurse Practitioner
Practitioner, Taussig
Taussig Cancer
Cancer Institute
Cleveland Clinic Foundation
Cleveland , Ohio
Learning Objectives:
Venous Thromboembolism and Peripheral
p
Neuropathy
Review the main coagulopathies in MM and their pathophysiology
Identify the indication for and types of thromboprophyllaxis used
iM
in M
MM
Identify nursing interventions for prompt diagnosis and early
treatment of coagulopathy in MM
Review therapies in MM that can cause PN and coagulopathies
List nursing interventions to decrease PN and coagulopathies
Case Study
48-year-old man started to notice increasing fatigue over a
period of 2 months "Working long hours"
Subjective
· Developed sharp "stabbing" lower back pain when playing football
with his
his son, rated 10/10
· Nothing alleviated the pain, so he went to the ED
History
· Nt
No contrib
ib t
u i
ting PMH
PMH
· No prior back trauma or pain
Case Study 1: Laboratory Values
Lab/Normal Reference Range
Value
Lab/Normal Reference Range
Value
WBC 3.011.0 k/L
8.72
BUN 825 mg/dL
38
Plt Ct
Ct 150 400
k/
k/ L
130 (L)
Creatinine 0 7
. 14
1.4 mg/dL
mg/dL
21(
2.1 H)
(H)
Hgb 13.017.0 g/dL
8.0 (L)
Calcium 8.510.5 mg/dL
10.6(H)
Hct 39.051.0%
23.1 (L)
Alb
i
um n 3 5
. 50
5.0 g/dL
/dL
34(
3.4 L)
(L)
MCV 80100 fL
94.6
Alk Phos 40150 U/L
148
RDW-CV 11.515.0%
14.7
Neut % 38.575.0%
54.0
B M
6(H)
2M
5.6 (H)
Abs Neut 1.007.50 k/L4.70
Case Study 1: Laboratory Values (cont.)
SPEP: Lab/Normal
Value
Lab/Normal Reference Range
Value
Reference Range
Range
MPA Serum IgG
5320
Alpha-1 0.110.22 g/dL
0.23
7171,411 mg/dL
MPA Serum IgA
28
Alpha-2 Globulin
0.78
78391 mg/dL
Bt G 0 50 100 /dL
063
MPA
MP Serum
Serum IgM
26
Beta G 0.501.00 g/dL
0.63
53334 mg/dL
MPA Serum Kappa
4860
Gamma Glob 0.601.35 g/dL
g
4.33
53412
1, 67
267 mg/dL
mg/dL
MPA Serum Lambda
< 30
M Spike (g/dL)
4.56 (H)
253653 mg/dL
Case Study (cont.)
Bone marrow biopsy: 50% plasma cells, kappa restricted
·
Cytogenetics: Normal male chromosome
·
FISH is negative for 17p, del (13)
(13), and t(4:14)
Skeletal survey
·
Widespread osteopenia and few lesions on calvarium , pelvis
Aggressive symptom control of disease-related anemia and renal
insufficiency is important
Many choices for initial therapy based on transplant candidacy
·
Bortezomib, lenalidomide, or thalidomide based
·
Clinical trial
Lets first review the diagnosis
g
and treatment of MM
NCCN, 2008.
What is Multiple Myeloma?
· Cancer of plasma cells
· Healthy plasma cells produce antibodies
antibodies
or immunoglobulins
· Part of our humoral immunity, they
yy are released in
response to foreign body invasion
· Myeloma cells produce abnormal
il
immunoglobulilin
· Overproduce monoclonal protein or paraprotein
· Ineffective immunoglobulins
immunoglobulins
· Leads to decreased bone marrow function
· Destruction of bone tissue, organ dysfunction
San Miguel JF, et al. Pathogenesis of Multiple Myeloma: Rationale for New and Novel Therapies. Clinical Care Options: Accessed 22 February, 2007.
http://clinicaloptions.com/Oncology/Treatment%20Updates/Myeloma/Modules/Pathophysiology/Pages/Page%203.aspx.
Criteria for Diagnosis of
Multiple Myeloma
py
Monoclonal plasma cells present in the bone
marrow 10%, and/or presence of a documented
lt
plasmacytoma
+
Presence of M component
component in serum and/or urine*
urine
+
One or more of the following (CRAB
g(
criteria)
· Calcium elevation (serum calcium >11.5 mg/dL)
· Renal insufficiency (serum creatinine >2 mg/dL)
· Anemia (hemoglobin <10 g/dL or 2 g/dL <normal)
· Bone disease (lytic lesions or osteopenia)
*Monoclonal M spike on electrophoresis IgG>3.5g/dL, IgA>2g/dL, light chain >1g/dL in 24-hr urine sample
Durie et al for the International Myeloma Working Group. Leukemia. 2006:1-7.
MM Treatment Options
Conventional chemotherapy:
·
Melphalan
·
Doxorubicin
·
Cyclophosphamide
Mainte
t nance
eace in MM
Steroid therapy:
·After transplant
· Dexamethasone
·Conventional therapy
· Prednisone
Novel therapeutics:
·
Thalidomide
·
Lenalidomide
·
Bortezomib
Stem cell transplantation:
·
Autologous
·
Allogeneic
Radiation therapy
Thalomid ® Prescribing Information, Revlimid ® Prescribing
Information; Velcade® Prescribing Information
Nurse Centric Model of Patient Care*
Patient Monitoring
Patient Management
Patient Counseling
Patient Research
Nurses are Central
Central to
Patient Management and
Healthcare Resource
Coordination
Patient Advocacy
Patient Education
* Developed by ScienceFirst, LLC; All Rights Reserved (www.science-first.com)
Effective Nursing Tools Improve Patient
Care and Treatment Outcomes
· Nurses play an essential role in managing
patient care, side effect management
· Nurses are key in efficiently and optimally
ii
managing emergent s d
ide f
e f
ffects
· Managing emergent side effects is an
important endeavor for
for improving MM
MM
patient care and treatment outcome
· Improving nursing assessment contributes
to positive outcomes
IMF-NLB `Consensus Statements' supplement In Press, CJON June 2008
Completion of `Consensus Statements'
Five consensus statements on the management of side
effects associated with the novel therapeutic agents
agents used
used
in treating multiple myeloma patients
1. Deep Vein Thrombosis / Pulmonary
py Embolism
2. Peripheral Neuropathy
3. Steroids Related Side Effects
4. Myelosuppression
5. Gastrointestinal Effects
IMF-NLB `Consensus Statements' supplement In Press, CJON June 2008
Novel Therapies:
Mechanisms of Action (MOA)
· Thalidomide
Immunomodulatory, anti-inflammatory, and anti-angiogenic agent
Suppresses production of TNF-
TNF , IL-
IL 6, and
and other cytokines
· Lenalidomide
Immunomodulatory agent with anti-angiogenic and anti-neoplastic
properties
Inhibits the secretion of
of pro-
pro inflammatory cytokines and increases
increases
the secretion of anti-inflammatory cytokines
· Bortezomib
The first drug in the class of "proteasome inhibitors"
A reversible inhibitor of 26S proteasome complex
Influences apoptotic, cell adhesion, and angiogenic pathways
· Doxil®
Used in combination with Velcade®
Reformulated version of the chemotherapeutic agent doxorubicin
Pegylated liposomal delivery
» Decreased immunoreactivity
» Increased bioavailability
Thalomid ® Prescribing Information, Revlimid ® Prescribing Information
Velcade® Prescribing Information
Case Study
· Diagnosis: IgG Lambda Multiple Myeloma
·ISS Stage III (Beta-2 5.6)
·Opted for a clinical study:
·Bortezomib, lenalidomide and dexamethasone in
newly diagnosed MM
·Transplant candidate
· Will have his stem cells harvested for a later transplant
(patient age, desire, performance status)
· Avoid melphalan
Case Study
·Expected side effects to educate patient
· Increased risk of VTE
Lenalidomide + steroids, individual risk needs to be assessed
· Risk to develop PN (Bortezomib)
Usually within the first 5 treatment cycles
Dose modification allows patients to remain on the effective anti-
cancer therapy
· Shingles Acyclovir/Valacyclovir prophyllaxis
· Myelosuppression
· GI, Steroids
· Nurses are integral to the assessment, early identification and
intervention of VTE, PN side effects
Lets review VTE and PN in MM
Overview of Thromboembolic Events (TE)
`Consensus Statement'
Cancer patients have a higher risk of TE events (7-10 fold) which
may lead to:
·
Deep vein thrombosis (DVT)
·
Pulmonary embolism (PE)
MM patients are at an increased risk for blood clots
·
Patients are at increased risk with high dose dexamethasone
treatment
·
The risk for DVT/PE is further increased in patients treated with
novel therapies
Thalidomide
Lenalidomide
·
In patients age >65
>65 years 5%
5% increase
increase chance to develop TE
Measures to prevent novel therapy-associated TE events include:
·
Mechanical
·
Myeloma regimen-related
·
Anticoagulant therapy (clot-preventing)
Individual and disease related risk factors must be assessed in
ALL patients with MM
TE events are serious
d
an potenti ll
a y lif
lt
e-a ering
d
an life-th
t
rea
i
en ng
Adapted from NLB Consensus Recommendations. In Press, CJON June 2008. Amir Qaseem et al., 2007, Ann Fam Med; J. B. Segal et al., 2007, Ann
Intern Med. http://www.nhlbi.nih.gov/health/dci/Diseases/Dvt/DVT_WhoIsAtRisk.htm
Pathophysiology of Cancer-Associated VTE
Prandoni et al., 2005.
PE - Signs/Symptoms
· Anxiety
· Sudden dyspnea
dyspnea
· Chest discomfort-increase w/ breathing
· Th
Tachycardi
dia, th
tachypnea
· Low grade fever, + Homans (35%)
· Pl
l
eura fri i
ct on
b
ru , crackl
kles f ll
o owed by
diminished breath sounds, wheezing
· ECG right
right axis deviation
deviation or
or new
new RBBB
PE is a Medical Emergency
gy
http://www.nhlbi.nih.gov/health/dci/Diseases/Dvt/DVT_SignsAndSymptoms.html
Adapted from NLB Consensus Recommendations. In Press, CJON June 2008
TE Event - Diagnostics
DVT
PE
· Doppler Ultrasound
·Ventilation Perfusion lung
(VQ) Scan
· Contrast Venography
·Spiral CT Scan
· D-Dimer
·D-Dimer
· Antithrombin Level
·Antithr
tt om
o bin
b
Lev
e el
e
To
i
ma t
n i
a n therapeutic level INR 2 3
-
http://www.nhlbi.nih.gov/health/dci/Diseases/Dvt/DVT_Diagnosis.html
Adapted from NLB Consensus Recommendations. In Press, CJON June 2008
TE Event - Prophylaxis
Mechanical
·
Sequential Compression
Compression Devices
·
Anti-embolism Stockings
·
Exercise Regimen
Pharmaceuticals - Therapy Dose
Dose Reductions
Reductions
·
Thalidomide: by 50mg increments from current dose
·
Dexamethasone
· 20- 40mg once weekly
· 20-
20 40mg days
days 1-
1 4 on
on 28d cycle
http://www.nhlbi.nih.gov/health/dci/Diseases/Dvt/DVT_Treatments.htm; Adapted from NLB Consensus Recommendations; In Press, CJON June 2008
Thalomid® Prescribing Information; Dexamethasone Prescribing Information
Treatment of VTE
Unfractionated heparin (UFH)
· Prevention: 5 000
,
units SC tid
· Treatment: IV infusion to target aPtt 2.02.9
· Frequently
qy responsible
p
for medication error
Low-molecular-weight heparin (LMWH)
· Prevention: Dalteparin 5,000 units/enoxaparin
40 mg/tinzaparin 4,500 units or 75 mg/kg all SC
daily
· Treatment: Dalteparin
Dalteparin 200 units/kg SC
SC daily
daily,
enoxaparin
1 mg/kg SC every 12 hours, tinzaparin 175 units/kg
SC daily
aPtt = activated partial thromboplastin times; SC = subcutaneous.
NCCN, 2008; Fragmin® prescribing information, 2007; Lovenox® prescribing information, 2007; Innohep® prescribing information, 2008.
Treatment of VTE
Factor Xa antagonist: Fondaparinux
· Prevention: 2.5 mg SC daily
· Tt
Treat
t
men : W i
e h
g t
ht bd
-based dosage scale SC
SC d i
a lily
Warfarin
· Chronic anticoagulation:
anticoagulation: 2.5
5 5
mg
mg po
po daily
daily, target
INR 2.03.0
Vena cava filter: Prevents PE with no evidence of
ti
preven ng DVT
Sequential compression devices: No bleeding risk,
continuous use, and impairs
impairs ambulation
Compression stockings: Little to no evidence of
effectiveness, possible adverse effects in patients
ith
w
cancer
INR = international normalized ratio.
NCCN, 2008; Arixtra® prescribing information, 2008.
Thromboembolic Events - Prophylaxis
Pharmaceutical
Agent
Suggested Dose
Salicylic Acid (aspirin)
SD 325mg or LD 81mg Daily
Unfractionated Heparin
5000 IU sq bid
Low Molecular Weight Heparin
- enoxaparin
40mg sq daily
- dalteparin
200IU/kg sc daily
Arixtra® fondaparinux
2.5mg sc daily
Warfarin
Weight based
· 1mg < 70kg
· 2mg 70kg
Prophylaxis tailored to individual patient's risk profile in consideration of
the International Myeloma Working Group consensus statement*
Palumbo et al., Leukemia (In press); Adapted from NLB Consensus Recommendations. In Press, CJON June 2008.
Amir Qaseem et al., 2007, Ann Fam Med; J. B. Segal et al., 2007, Ann Intern Med.
General Strategic Recommendations for the
Management of TE Events
Prophylactic measures which can reduce or eliminate
TE risk (especially in the first
first 3-
3 6
- mos)
mos) include:
include:
· Aspirin; suggested for patients with no or one risk
factor
· Low molecular weight heparin or full dose warfarin for
patients with two or more risk factors
· Low molecular weight
weight heparin or full dose warfarin
warfarin for
for
all patients with therapy-related risks including:
High dose dexamethasone
Doxorubicin
Multi-agent chemotherapy
Renal disease
ESAs
Obesity
Adapted from NLB Consensus Recommendations. In Press, CJON June 2008
http://www.nhlbi.nih.gov/health/dci/Diseases/Dvt/DVT_Treatments.html
Case Study
Our patient did not have a history of prior blood clot
but did have:
· BMI over 30 (obese)
· Renal disease
disease (may be reversed but still remains high)
high)
· Multi-agent chemotherapy
·Based on these risk factors for VTE, would you
ti
an cipate your
ti
pa ent to be on Aspirin 81 100
-
mg d i
a lily
or LMWH for VTE prophyllaxis?
·He has greater
g
than 1 risk factor so he needs to remain
on LMWH for VTE prophyllaxis for now
Overview of Peripheral Neuropathy (PN)
`Consensus Statement'
· Anti-myeloma therapies can lead to PN
· PN is a challenging
challenging adverse event which
which may:
· Affect quality of life
· Compromise optimal treatment
· Management strategies include:
· Ongoing evaluation
· Dd
Dose and
h
sc
d
e
l
u e
d
mo ifi
dificati
tions
· Pharmacologic interventions
· Non-pharmacologic approaches
· Patient education
Adapted from NLB Consensus Recommendations. In Press, CJON June 2008, Thalomid® Prescribing Information, Velcade® Prescribing Information
Colson et al., 2004, Clinical Journal of Oncology Nursing; S. Lonial, 2007, The American Journal of Hematology/Oncology.
Peripheral Neuropathy (PN):
General Concepts
Patients with MM are at risk for PN based on the biology of the disease
· Pt
Pa i
ti
t
en s can have PN
PN even b f
e ore treat
t
men has begun up to
13%
PN can lead to structural damage in the peripheral nerves of the central
nervous
t
sys em
"Stocking-glove" distribution
Sensory comp
yponent of neuropathy has 2 primary typ
ypes
· Small fiber: Pin-prick, pain and temperature
· Large fiber: Vibration and proprioception
CIPN = chemotherapy-induced peripheral neuropathy.
Armstrong et al, 2005. Ropper & Gorson, 1998
PN Definition, Signs/Symptoms
Damage to the peripheral nervous system including any injury,
inflammation, or degeneration of peripheral nerve fibers
Signs/symptoms
Severe symptoms
· Temporary Numbness
· Burning Pain
· Tingling
· Muscle Wasting
Wasting
· Parasthesias
· Paralysis
· Sensitivity to Touch
ouc
· Orga
Og n
a Dys
y f
s un
u ct
c i
t on
· Muscle Weakness
Adapted from NLB Consensus Recommendations. In Press, CJON June 2008
http://www.ninds.nih.gov/disorders/peripheralneuropathy/detail_peripheralneuropathy.htm
Factors Contributing to CIPN
·
Older age
·
Chemotherapy dose, cumulative dose
·
Prior cisplatin or vinca alkaloids
·
Therapy duration
·
Co-administration of other neurotoxic agents
·
Pre-existing conditions such as diabetes, alcoholism, HIV
positive, female gender, Vit B12
B12 deficiency
·
AL amyloidosis
Wickham, 2007
Some Proposed Mechanisms
Underlying PN in MM
·
Damage to neuronal cell bodies in the DRG
·
Axonal toxicity (demyelination, impaired transport)
·
Axonal membrane ion channel dysfunction
(N +
a
h
c
l)
anne
·
Mitochondrial damage and inflammation (bortezomib)
DRG = dorsal root ganglion; Na = sodium.
Windebank et al, 2008; Bhagra et al, 2007; Kirchmair et al, 2007.
Novel Agents Associated
With PN in MM
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 treatedh
d hadP
d N(
PN (regardl
dless of prior th
therapy)
Thalidomide
· Grade 1/2 PN occurs in 80% pts previously treated
·Grade 3/4 PN can occur in ~ 4% when combined with
dexamethasone; all grades 53.9% when combined with
dexamethasone
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.
Chemotherapy Agents Associated
With PN in MM
Agent
Incidence of PN
Cisplatin
· Not routinely administered to MM patients except in
relapsed/refractory disease
·Incidence of PN is approximately 50%
· PN when cumulative doses exceed 300 mg/m2 (or rarely at lower
d/
doses/various d
a
i
m nistration
h
sc
d
e ules)
· Occurs in up to 90% of cumulative doses > 500 mg/m2
Vincristine
·Used to be given with VAD regimen, DVD
· Cumulative dose of 10 mg causes stocking-glove sensory loss,
areflexia, pain; can cause autonomic neuropathy; 1/3 report
continued symptoms post-treatment
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.
Ways to measure PN in MM
· NCI Common Terminology Criteria for Adverse
Events (CTCAE) v3.0
· PN toxicity grade
· Allows for systematic reporting in clinical trials
· Neurotoxicity Assessment Tool
(FACT- GOG-ntx)
· Patient report of symptoms
· Used for dose modification of bortezomib in several
clinical trials
· Reduction of bortezomib for PN allowed patients to
receive more cumulative doses of bortezomib and
lessened severity of PN
NCI CTCAE criteria. On-line. Available: http://ctep.cancer.gov/forms/CTCAEv3.pdf; Richardson et al, 2009
PN and Pain Toxicity Grades
Grade 1
Grade 2
Grade 3
Grade 4
Grade 5
Mild
Moderate
Severe
Life-threatening or
Death
disabling
Mild pain not
Moderate pain
Severe pain
Disabling
N/A
interfering with
interfering with function
severely
function
but not ADL
interfering with
ADL
Asymptomatic,
Symptomatic weakness
Weakness
Life-threatening
Death
weakness on
interfering with function
interfering with
disabling
testing only
but not ADL
ADL
Asymptomatic,
Sensory alteration or
Sensory
Disabling
Death
loss of deep
paresthesias interfering
alteration or
tendon reflexes or
with function not with
paresthesias
paresthesias
ADL
interfering with
with
ADL
Gd
Gra i
ding based upon:
Common Terminology Criteria for Adverse Events (CTCAE) v3.0
http://ctep.cancer.gov/forms/CTCAEv3.pdf
Adapted from NLB Consensus Recommendations. In Press, CJON June 2008
PN: FACT-GOG Neurotoxicity Assessment Tool
Instructions for Patients
Instructions for Healthcare Professionals
By circling one number per line, please indicate how true each
This assessment tool is provided to help you
statement has been for you during
yg the past
p
seven days
y , using the
evaluate peripheral
pp
neuropath
p
y in patients
p
receiving
following scale:
chemotherapy. Healthcare professionals may find
discussion of patients' responses helpful in
0 = not at all
determining the grade of neuropathy as defined by
1 = a little bit
the National Cancer Institute Common Terminology
2 = somewhat
Criteria for Adverse Events; however, no direct
3 = quite a bit
correlation exists between assessment scores and
4h
4 = very much
to icit
x
y grades.
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
feel discomfort in
in my
my hands
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
hav trouble
trouble hearing
hearing.
0
1
2
3
4
I get a ringing or buzzing in my ears.
0
1
2
3
4
I have trouble buttoning buttons.
0
1
2
3
4
I have trouble feeling the shape of small objects when they are in my hands.
0
1
2
3
4
I have
hav trouble
trouble wal
wa k
l i
k ng
ing.
0
1
2
3
4
Calhoun, et al. Proceedings of the American Society of Clinical Oncology 2000.; Cella, 1997;Cella, et al. Journal of Clinical
37
Oncology 1993.; http://ctep.cancer.gov
PN Dose/Schedule Modifications
Bortezomib Therapy
·
Currently, dose modification of bortezomib and
thalidomide is the most effective management
strategy
·
Grade 1 with pain or Grade 2: Reduce dose to 1
mg/m2
mg/m
·
Grade 3 or Severe: Hold therapy PN resolves
to baseline
· Restart at 0.7 mg/m2
· Consider changing treatment to once weekly
·
Gd
Grade 4: D/C
D/C th
therapy
Velcade® Prescribing Information; http://ctep.cancer.gov/forms/CTCAEv3.pdf; Adapted from NLB Consensus Recommendations. In Press, CJON 2008; ACS, 2005; Armstrong et al, 2005,
Oncology Nursing Forum; Colson et al., 2004, Clinical Journal of Oncology Nursing; NCCN 2007; NINDS, 2007; Tariman, 2003, Clinical Journal of Oncology Nursing; Visovsky et al., 2007,
http://www.ons.org/outcomes/volume2/peripheral/pdf/PEPCardDet_peripheral.pdf
PN Dose/Schedule Modifications
(cont'd)
()
Thalidomide Therapy
Grade 1 or
or Mild:
Mild:
· Continue therapy
Grade 2 or Moderate:
· Intermittent Continue therapy
· Continuous Stop therapy and observe whether
symptoms persist
· If symptoms resolve Restart therapy at a reduced dose
Grade 3 or Severe:
· Hold therapy until PN resolves to baseline
· Once symptoms resolve Restart therapy at a reduced dose
Grade 4 or Disabling:
· Discontinue therapy permanently
permanently
Adapted from NLB Consensus Recommendations. In Press, CJON June 2008; Thalomid® Prescribing Information;
http://ctep.cancer.gov/forms/CTCAEv3.pdf; Colson et al., 2004, Clinical Journal of Oncology Nursing; NCCN 2007; NINDS, 2007; Tariman, 2003, Clinical Journal of Oncology Nursing;
Visovsky et al., 2007, http://www.ons.org/outcomes/volume2/peripheral/pdf/PEPCardDet_peripheral.pdf.
Cisplatin and Vincristine
· Less commonly used in MM with newer agents
available
· Patients are living longer may receive these therapies
at some point
· Closely monitor for PN signs and symptoms with each
dose as dose reduction may be indicated
Bortezomib/Melphalan/Prednisone/Thalidomide
Bortezomib/Thalidomide
A Phase III Study of VMPT Followed by Maintenance with Bortezomib and Thalidomide
for Initial Treatment of Elderly Multiple Myeloma Patients
Study Objective:
·
Compare VMPT with a maintenance regimen including Bortezomib and Thalidomide
with VMP without
without a maintenance
maintenance regimen
Study Design:
·
Prospective, randomized
Bortezomib
1.3 mg/m2 Melphalan
p
9 mg/m2
Days 14
Bortezomib
1.3 mg/m2
Days 1, 15
Prednisone
60 mg/m2
Days 14
Thalidomide 50 mg/day
continuously
Thalidomide 50 mg
Days 142
Bortezomib 1.3 mg/m2 Melphalan
9 mg/m2
Days 14
No Maintenance
Prednisone
60 mg/m2
Days 14
·
Both regimens amended to 9 5-week cycles
·
Bortezomib modified to weekly administration (days 1,8,15,22)
41
Palumbo et al, Blood 114, Abstract 128, 2009
Conclusions from VMPT VT vs. VMP
Study Arm
PR, %
VGPR, %
CR, %
2Y PFS, %
2Y OS, %
VMPT-
VMPT VT
86
55
34
70
89.6
VMP
79
47
21
58.2
89.0
p-Value
0.02
0.07
0.0008
0.0008
0.84
VMPT followed by VT was superior to VMP for response rates and PFS
The weekly infusion of Bortezomib significantly reduced the incidence of grade 3-4 peripheral
neuropathy
·
From 18% to 4% (p=0.0002) in VMPT arm
·
From 13% to 2% (p=0.0003) in VMP arm
This is the first report showing the superiority of a 4-drug regimen followed by maintenance
compared to standard therapy (VMP)
Weekly infusion of bortezomib effective and less PN
42
Palumbo et al, Blood 114, Abstract 128, 2009
General Strategic Recommendations for
the Management of PN
Patient Education
· Notify if S/S Worsen
· Home safety with
with decreased
decreased sensation in
in extremities
· Is driving appropriate?
· Family members to assess hot/cold temperatures if
patient is
is unable to
to do
do so
so
Non-Pharmaceutical
· Gentle massage of affected areas with cocoa butter,
capsaicin cream
· Home Health Referral to review safety at home
· Assistance with ADL
· Referrals: Pain management, neurology,
physical/occupational therapy
Adapted from NLB Consensus Recommendations. In Press, CJON June 2008; NCCN 2007; NINDS, 2007; Tariman, 2003,
Clinical Journal of Oncology Nursing; Visovsky et al., 2007, http://www.ons.org/outcomes/volume2/peripheral/pdf/PEPCardDet_peripheral.pdf.
General Strategic Recommendations for
the Management
g
of PN (cont'd)
()
For all patients prior to therapy
·
B-
B complex vitamins
vitamins including
including B1
B , B6
B6, B12
B12 (at least
least 400 mcg)
·
Folic Acid 1 mg daily
For grades 2 or higher
·
Tricyclic antidepressants (i.e. amitriptyline, despiramine)
·
TA
Try A i
m no A i
c d
ids (eg,
t
ace l
y L
iti
-carn ne, L lt
-glutamine
d
an alh
lpha
lipoic acid) on an empty stomach
·
Neurontin®, Lyrica®, Cymbalta®
·
May apply Lidoderm® Patch 5% to affected area every 12 hours
Adapted from NLB Consensus Recommendations. In Press, CJON June 2008, Colson et al., 2004, Clinical Journal of Oncology Nursing; NCCN 2007; NINDS, 2007; Tariman, 2003, Clinical
Journal of Oncology Nursing; Visovsky et al., 2007, http://www.ons.org/outcomes/volume2/peripheral/pdf/PEPCardDet_peripheral.pdf; Endo Pharmaceuticals; 2006; Lidoderm® (lidocaine
patch 5%) prescribing information; http://www.mayoclinic.com/health/peripheral-neuropathy/BN00046
Case Study
After Cycle 4 of bortezomib, your patient reports a mild
loss of sensation (grade
(grade 1)
1) b t
u starts
starts to
to feel
feel pain hen
w
standing on his feet for longer than ˝ hr at a time.
What would you consider to be effective?
·
Discontinue bortezomib
d
an
i
sw t
itch to
t
ano h
ther drug
before the PN worsens
·
Hold bortezomib and restart at a reduced dose when the
PN resolves.
·
Continue with the current dose and schedule as the pain
is likely to resolve with time
·
Start oxycontin
oxycontin and oxycodone
oxycodone to manage the pain
pain and
and
continue current dose
·
Start pregabalin and discontinue bortezomib if they are
in remission
Summary
·Nurses are integral to management of patients
·Patients will be more likely to adhere to the prescribed
regimen if side effects are appropriately addressed and
manage
·Never underestimate your role as a provider and
liason!
·More to come from NLB.... SURVIVORSHIP!
Educational Resources
·
American Cancer Society
·
National Cancer Institute
·
International Myeloma Foundation
- IMF Myeloma
Myeloma Today
T
Newsletter
Newsletter
- 1 800 425 CURE
- IMF Website
Website
www.myeloma.org
· Thank you!
CE CREDIT
·
There are no prerequisites or fees for participating in and receiving
credit for this activity.
y
·
Participants must 1) study the educational activity, 2) download and
complete the posttest and evaluation form provided in your confirmation
email, 3) mail, e-mail or fax the completed forms to Medical Education
Resources at
· Mail: Medical Education Resources
1500 W. Canal Court, Building B
Littleton, CO
CO 80120-6404
· Fax:720-449-0217
· E-mail: Kathryn Holland, kathryn@mer.org
·
A statement off
f credit will be issued only upon receipt of a completed
activity form and a completed posttest with a score of 70% or better.
Statements of credit will be mailed within 6 weeks of the activity.
ACCREDITATION
·
This continuing education activity provides a maximum of 1.0
tt
contact hours f
o R
i
eg stered Nursing C d
re it
dit
·
Medical Education Resources is an approved provider of
continuing nursing education by the California Board of
Registered Nursing, Provider #CEP 12299.
·
Please email Diane Moran at the International Myeloma
Foundation if you have any
yy questions.
q
dmoran@myeloma.org