Nursing Considerations With the Use of Targeted Therapy

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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

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Differentiation
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Normal HER2 expression
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HER2 amplification leads toHER2 overexpression
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HER2 overexpression leads totumour proliferation
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Binding of Herceptin to HER2
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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. 2006425.
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• Some Examples

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Avastin

• Bevacizumab

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Normal Angiogenesis in Adults
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Tumour Angiogenesis
5. Intravasation
1. Secretion of angiogenic factors
Tumour
4. Appearance of new tumour vasculature
2. Proteolytic destruction of extracellular
matrix
3. Endothelial cell proliferation and migration
Sprouting capillary
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Avastin effects on human tumor vasculature
Avastin
Normalized
Normal
Abnormal
Reduces interstitial fluid pressure vessel
density Increases drug delivery
Adapted from Jain RK. Nat Med 200179879 Willett
CG et al. Nat Med 2004101457 Tong R et al.
Cancer Res 20046437316
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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.
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Serious Adverse Events
Adverse Event Bevacizumab 10 mg/kg (N39) Bevacizumab 3 mg/kg (N37)
Epistaxis 21 14
Hypertension 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
Chest pain 5 (5) 0
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 gt3.5 g of protein per 24 hrs
Yang CH et al. N Engl J Med. 2003349427.
ALT Alanine Aminotransferase
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• Adverse Events Nursing Considerations

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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. 200461(Suppl
5)21.
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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. 200461(Suppl
5)21.
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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. 200461(Suppl
5)21.
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Erbitux

• Cetuximab

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EGFR inhibition by agents that target the EFGR
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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

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Erbitux Safety And Tolerability

• Nail disorders, e.g. paronychia
• Eye disorders
• Respiratory disorders
• Infusion-related reactions (IRRs)
• mild to moderate reactions gt 10 of patients
• severe reactions 1-10 of patients

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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

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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

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Mabthera

• Rituximab

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MabThera anti-CD20 Monoclonal Antibody
1 ADCC2 Complement activity3 Sensitising
chemoresistant B-cells4 Induction of apoptosis
2
3
4
NK cell
1
B-cell (CD20-positive)
NK natural killer
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MabThera administration

• 375mg/m2 (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

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MabThera pivotal trial in low-grade or follicular
NHL adverse events (n166)
180 160 140 120 100 80 60 40 20 0
NCI toxicity grade
Grade 1 Grade 2 Grade 3 or 4
Number of patients
First Second Third Fourth
Infusion
McLaughlin P, et al. Semin Oncol 1999267987
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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

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What special nursing considerations are
necessary? (contd)

• 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
  (gt25,000/µL)

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What adverse events might patients experience
with single-agent MabThera?
Figures based on events reported in ³5 of 356
patients
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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

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• Oral Targeted Therapy

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Sutent

• Sunitinib

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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.
20032471. 2. Motzer RJ. JAMA. 20062952516.
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Most Common Adverse Events (20)
Adverse Event All Grades ()
Fatigue 58
Diarrhea 58
Nausea 49
Altered taste 44
Mucositis/stomatitis 43
Anorexia 38
Hypertension 30
Bleeding 30
Vomiting 28
Dyspepsia 28
Rash 27
Abdominal pain 22
Hand-foot reaction 21
Sutent (sunitinib) Full Prescribing Information.
Pfizer Inc. October 2007.
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Sunitinib and Sorafenib Adverse Events

• Nursing Considerations1,2

1. Wood LS. Oncology Nurs News. 2007319. 2.
Wood LS. Oncology Nurs News. 2007437.
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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

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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. 2007319. 2.
Wood LS. Oncology Nurs News. 2007437.
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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. 2007319. 2.
Wood LS. Oncology Nurs News. 2007437.
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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

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Hypertension

• Common side effect with this class of drug
• Baseline BP reading is essential
• Monitor BP weekly x 6
• gt20 mg/m increase in diastolic or gt150/100
  warrants intervention
• Antihypertensive agents may need to be added or
  increased during therapy

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• Targeted Therapies

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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.
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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.
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Any Questions ?