Transcript Document

Nursing Considerations
With the Use of Targeted
Therapy
Fadi Sami Farhat
Head of Division Hematology Oncology,
Hammoud Hospital University Medical Centre,
Lecturer St-Joseph University
LPA,
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ET, etc.
TGFa
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EGF
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Apoptosis
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b-cellulin HB-EGF
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Amphiregulin
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Cytokines
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Ligands
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Receptor
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PLCg
PI3K
Shp2
PKC
Grb2
GAP
Myc
Migration
Jun
Fos
Elk
Growth
Nck
Sos
RAF
MEK
MAPK
Akt
Bad S6K
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Sp1
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Epiregulin
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Vav
Grb7
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Adaptors
and enzymes
Rac
PAK
JNKK
JNK
Egr1
Abl
Stat
Adhesion
Cascades
Transcription
factors
Differentiation
Normal HER2 expression
HER2 amplification leads to
HER2 overexpression
HER2 overexpression leads to
tumour proliferation
®
Binding of Herceptin to HER2
New Challenges For Oncology Nurses
 Understanding new mechanisms of actions
 Toxicities are highly variable among patients
 Unique side-effect profiles
 Proactive side effect management
 Controls disease vs. curing disease
 Some medications: Oral administration and
decreased patient/nurse interaction
Moldawer N, Wood LS. Kidney Cancer J. 2006;4:25.
Some Examples
Avastin
Bevacizumab
Normal Angiogenesis in Adults
Tumour Angiogenesis
5. Intravasation
1. Secretion of
angiogenic
factors
2. Proteolytic
destruction of
extracellular matrix
Tumour
4. Appearance
of new
tumour
vasculature
3. Endothelial
cell proliferation
and migration
Sprouting capillary
®
Avastin : effects on human tumor
vasculature
Avastin
Normal
Abnormal
Normalized
Reduces
interstitial fluid pressure
vessel density
Increases
drug delivery
Adapted from Jain RK. Nat Med 2001;7:987–9
Willett CG et al. Nat Med 2004;10:145–7
Tong R et al. Cancer Res 2004;64:3731–6
Dosing and Administration
 Usual dosage of bevacizumab in the treatment of :

Colorectal, breast, lung cancer -5 mg/kg IV every 2
weeks

renal cancer is 10 mg/kg IV every 2 weeks 1,2
 Can be associated with hypersensitivity reactions
during administration
1. Avastin® (bevacizumab) Full Prescribing Information. Genentech, Inc. March 2008.
2. National Cancer Institute website. http://www.cancer.gov/clinicaltrials/search.
Serious Adverse Events
Bevacizumab 10 mg/kg
(N=39) %
Bevacizumab 3 mg/kg
(N=37) %
21
14
36 (21)*
3
Fever without infection
10
3
Malaise
33
16
Hematuria
13
3
Hyponatremia
8
11
Proteinuria
64 (8)*
41 (5)*
Elevated ALT
10
5
5 (5)*
0
Adverse Event
Epistaxis
Hypertension
Chest pain
* Percent of patients with grade 3 toxic effects
 ≥1+ or ≥150 mg/24 hrs
Grade 3 hypertension was defined as hypertension not completely controlled by one standard medication
Grade 3 proteinuria was defined as urinary excretion of >3.5 g of protein per 24 hrs
ALT = Alanine Aminotransferase
Yang CH et al. N Engl J Med. 2003;349:427.
Adverse Events:
Nursing Considerations
Bleeding
 Obtain patient history of unusual bleeding or clotting,
GI perforation, and use of anticoagulants
 Avoid anticoagulant therapy if possible,
 Educate patient about signs of bleeding (ie, epistaxis;
bleeding gums during tooth brushing; red or black,
tarry stools; vomiting blood)
Ignoffo RJ. Am J Health-Syst Pharm. 2004;61(Suppl 5):21.
Thrombosis & Proteinuria
 Educate patient about signs of thrombosis that include

Sudden chest pain

Difficulty breathing
 Monthly monitoring of renal function and urine protein
concentration
Ignoffo RJ. Am J Health-Syst Pharm. 2004;61(Suppl 5):21.
Hypertension
 Establish baseline BP, monitor weekly during therapy
 Ensure that patient has a BP monitor at home
 Continue antihypertensive therapy in patients already
taking it when bevacizumab is initiated
 Initiate mild antihypertensive if patient develops
hypertension during bevacizumab therapy
Ignoffo RJ. Am J Health-Syst Pharm. 2004;61(Suppl 5):21.
Erbitux
Cetuximab
EGFR inhibition by agents that target the
EFGR
Erbitux Recommended Dosing Schedule
 Once a week:

an initial 400 mg/m2 2-h infusion, d1, week 1

subsequent 250 mg/m2 1-h infusions weekly from d1,
week 2
 Anti-allergic premedication (such as an
antihistamine) must be used prior to the initial
infusion and is recommended prior to all
subsequent infusions
Erbitux Safety And Tolerability
 Nail disorders, e.g. paronychia
 Eye disorders
 Respiratory disorders
 Infusion-related reactions (IRRs)

mild to moderate reactions > 10% of patients

severe reactions : 1-10% of patients
Erbitux : Skin reactions
 Common feature of treatment with many EGFR inhibitors
 In approx. 80% of patients treated with ERBITUX

85% are mild-to-moderate
 Acne-like rash (face, scalp, upper chest or back )
 Pruritus, dry skin and nail disorders - less frequently
 Generally manageable, rarely - discontinuing treatment
 Majority - within the first 2-3 weeks and generally resolve,
without sequelae, after cessation of treatment
Correlation between skin reactions and
response to treatment with Erbitux
 The presence and/or intensity of skin reactions
correlates strongly with response to ERBITUX and
survival
 This relationship has been observed in different tumor
types, including CRC and SCCHN
 However, patients not developing skin reactions may
also respond to treatment with ERBITUX
Mabthera
Rituximab
MabThera : anti-CD20 Monoclonal
Antibody
2
1 = ADCC
2 = Complement activity
3 = Sensitising chemoresistant B-cells
4 = Induction of apoptosis
3
4
NK
cell
1
B-cell
(CD20-positive)
NK = natural killer
MabThera administration
2
 375mg/m (Do not administer as i.v. push or bolus)
 Premedication, about 1 hour before start of infusion:


analgesic (i.e. paracetamol 1,000mg p.o.)
antihistamine (i.e. clemastine 2mg i.v. or p.o.)
 First infusion must be applied in the hospital setting
 Second infusion can be applied on an outpatient basis if no
allergic reactions were present during the first infusion
Number of patients
MabThera pivotal trial in low-grade or
follicular NHL: adverse events (n=166)
180
160
140
120
100
80
60
40
20
0
NCI toxicity grade
Grade 1
Grade 2
Grade 3 or 4
First
Second
Third
Infusion
Fourth
McLaughlin P, et al. Semin Oncol 1999;26:79–87
What special nursing
considerations are necessary?
Safety measures
 Supervision available at all times by an experienced
clinician
 Stop antihypertensive medication 12 hours before
infusion
 Stop other protein-based drugs, e.g. interferons,
mistletoe-based drugs
 Should not be administered to pregnant women
What special nursing considerations are
necessary? (cont’d)
Adverse events
 With the first infusion
 With elevated infusion rates
 infusion reaction
 In high-risk patients
 high tumour burden (bulky disease)
 elevated lymphocyte count in peripheral blood
(>25,000/µL)
What adverse events might patients
experience with single-agent MabThera?
Event
All grades* (%)
Grade 3/4 (%)
Fever
48.3
0.6
Chills
31.7
2.2
Headache
12.6
0.6
Nausea
17.1
0.3
Hypotension
9.8
0.8
Angioedema
10.7
0.3
7.9
1.4
Bronchospasm
*Figures based on events reported in 5% of 356 patients
What actions should be taken should
serious adverse events occur?
 If serious adverse events occur, e.g. fever, chills,
hypotension

stop MabThera infusion

open saline infusion line

call for clinician

bed in top-down position and monitor closely

restart at 50% reduction in rate upon
resolution of symptoms
Oral Targeted Therapy
Sutent
Sunitinib
Dosing and Administration
 An orally administered tyrosine kinase inhibitor (TKI)
 Approved for treatment of advanced RCC in January 2006
 Potent inhibitor of VEGFR, PDGFR, and FLT-31
 May be taken with or without food
 Drug formulation: 50 mg, 25 mg and 12.5 mg capsules
 Requires dose adjustment when administered with CYP3A4
inhibitors or inducers2
 Important to assess concomitant medications
50 mg daily x 28 days followed by 14 day rest period
1. Abrams TJ et al. Mol Cancer Ther. 2003;2:471.
2. Motzer RJ. JAMA. 2006;295:2516.
Most Common Adverse Events (≥20%)
Adverse Event
All Grades (%)
Fatigue
Diarrhea
Nausea
Altered taste
Mucositis/stomatitis
Anorexia
Hypertension
Bleeding
Vomiting
Dyspepsia
Rash
Abdominal pain
Hand-foot reaction
58
58
49
44
43
38
30
30
28
28
27
22
21
Sutent® (sunitinib) Full Prescribing Information. Pfizer Inc. October 2007.
Sunitinib and Sorafenib
Adverse Events
Nursing Considerations1,2
1. Wood LS. Oncology Nurs News. 2007;3:19.
2. Wood LS. Oncology Nurs News. 2007;4:37.
Diarrhea
 Treat initially with diet modification (low residue) and
loperamide – consider fluid replacement as necessary
 If loperamide insufficient, atropine ?
 Additional options include tincture of opium, Culturelle
(oral probiotic), and Activia yogurt containing
bifidobacterium
 May be a dose limiting toxicity
Fatigue & Functional or clinical
mucositis
 Adjust activities to allow for rest periods and maximize
fluid and caloric intake
 Greater intensity during initial months of treatment
 Avoidance of carbonated beverages and spicy foods
 Eating foods at room temperature
 Can be a dose limiting side effect
1. Wood LS. Oncology Nurs News. 2007;3:19.
2. Wood LS. Oncology Nurs News. 2007;4:37.
Taste changes and anorexia &
Medications
 Maximize caloric intake
 Encourage 6 small meals per day
 Use of flavorings and gravy to enhance food taste
 Topical lidocaine or Xylocaine
 BMX Solution (Benadryl/Mylanta/Xylocaine)
 Rincinol (OTC topical solution containing aloe vera)
 Nystatin suspension or clotrimazole troches for clinical
mucositis
1. Wood LS. Oncology Nurs News. 2007;3:19. 2. Wood LS. Oncology Nurs News. 2007;4:37.
Dermatologic Toxicities
 Dry skin, Rash, Hand-foot skin reaction, Hair:

Alopecia, Thinning, De-pigmentation, Scalp pruiritis/burning
 Application of lotions/creams as part of initial education
 Avoid hot showers/steam
 Rash may present in many ways

Maculopapular, Exfoliative dermatitis, Acneform, Erythema
multiform-appearing eruptions
Hypertension
 Common side effect with this class of drug
 Baseline BP reading is essential
 Monitor BP weekly x 6
 >20 mg/m increase in diastolic or >150/100 warrants
intervention
 Antihypertensive agents may need to be added or
increased during therapy
Targeted Therapies
Patient Education and Management
 Assess patient at initiation of therapy and reinforce
treatment goals, treatment schedule and duration of
therapy
 Ensure that patient sees an MD or RN at the beginning
of each treatment cycle
 Instructions about cancer treatment and side effect
management
Moore SH. Online educational activity – 2006.
Patient Education and Management
 Patient should be instructed to contact healthcare
provider immediately when experiencing any side
effects
 Targeted therapies have manageable side effects with
appropriate nursing interventions
 Patients have prolonged survival with control of their
cancer
Moore SH. Online educational activity – 2006.
Any Questions ?