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, thrombin ET, etc.
TGF a (1) EGF (1) Epiregulin (1,4) b -cellulin (1) HB-EGF (1,4) Amphi regulin (1) NRG1 (3,4) a b NRG2 (4) a b NRG3 (4) NRG4 (4) Cytokines Ligands Input layer 1 3 1 2 1 1 2 2 4 2 1 4 3 2 4 4 3 4 3 3 Receptor dimers Signal processing layer Src Cbl PLC g PI3K Shp2 GAP Ras-GDP Ras-GTP Shc Grb2 Sos PKC Bad Akt S6K RAF MEK MAPK PAK JNKK JNK Nck Vav Rac Grb7 Crk Jak Adaptors and enzymes Abl Cascades Sp1 Myc Jun Fos Elk Egr1 Stat Output layer Apoptosis Migration Growth Adhesion 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
1.
Secretion of angiogenic factors 2.
Proteolytic destruction of extracellular matrix
Tumour
3.
Endothelial cell proliferation and migration 5.
Intravasation 4.
Appearance of new tumour vasculature Sprouting capillary
Avastin
®
: effects on human tumor vasculature
Avastin Normal Abnormal Reduces interstitial fluid pressure Normalized 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
Adverse Event Bevacizumab 10 mg/kg (N=39) % Bevacizumab 3 mg/kg (N=37) %
Epistaxis Hypertension Fever without infection Malaise Hematuria Hyponatremia Proteinuria Elevated ALT Chest pain 21 36 (21) * 10 33 13 8 64 (8) * 10 5 (5)* 14 3 3 16 3 11 41 (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 >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/m 2 2-h infusion, d1, week 1 subsequent 250 mg/m 2 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
3 2
1 = ADCC 2 = Complement activity 3 = Sensitising chemoresistant B-cells 4 = Induction of apoptosis
4
NK = natural killer B-cell (CD20-positive)
1 NK cell
MabThera administration
375mg/m 2 (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
MabThera pivotal trial in low-grade or follicular NHL: adverse events (n=166) 180 160 140 120 100 80 60 40 20 0 First NCI toxicity grade Grade 1 Grade 2 Grade 3 or 4 Second Infusion Third 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 Fever Chills Headache All grades* (%) 48.3 31.7 12.6 Nausea Hypotension 17.1 9.8 Angioedema 10.7 Bronchospasm 7.9
*Figures based on events reported in
5% of 356 patients
Grade 3/4 (%) 0.6 2.2 0.6 0.3 0.8 0.3 1.4
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-3 May be taken with or without food 1 Drug formulation: 50 mg, 25 mg and 12.5 mg capsules Requires dose adjustment when administered with CYP3A4 inhibitors or inducers 2 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
Fatigue Diarrhea Nausea Altered taste Mucositis/stomatitis Anorexia Hypertension Bleeding Vomiting Dyspepsia Rash Abdominal pain Hand-foot reaction
All Grades (%)
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 Considerations
1,2 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.