Symptom Management of Treatment Toxicities in
Early Breast Cancer Patients
Frances M. Palmieri, RN, MSN, OCNClinical Nurse Specialist
Manager, Multidisciplinary Breast Clinicand Breast Cancer Program
Mayo ClinicJacksonville, FL
Overview
• Introduction to EBC • Taxanes in HER2 Overexpressing Breast
Cancer • Symptom Management and Patient Support
Strategies– Hematologic; Focus on Non-Hematologic
Toxicities:• Fatigue• Chemotherapy induced sensory peripheral
neuropathy, alopecia, arthralgia/myalgia, mucositis and hypersensitivity reactions
EBC = early breast cancer.HER2 = human epidermal growth factor receptor 2.
United States
Deaths per year 40 970
(212 per day )
Diagnoses per year 212 920
(583 per day)
Breast Cancer Statistics
Jemal A et al. CA: A Cancer Journal for Clinicians. 2006; 56(2):106-130
Invasive Early Breast Cancer Demographics
• Incidence increases with age
– Postmenopausal women make up 80% of all patients with BC
• Incidence BC remains high, but mortality rates have declined in the United States– Reflects advances in early detection, diagnosis, and treatment,
such as novel treatment therapies and advanced
imaging/screening
– Digital Mammography or MRI
• 5-year relative survival rates range from 92% for stage IIA disease to 54% for stage IIIB disease
BC = breast cancer; MRI = magnetic resonance imaging. American Cancer Society. Cancer Facts and Figures 2006. http://www.cancer.org. Accessed December 31, 2007.
Different Types of Breast Cancer
• Early stage vs metastatic• HER2+• Hormone receptor positive (ER+, PR+)• Triple negative• Inherited breast cancer
– BRCA1, BRCA2, and other genes• New classifications of BC are being defined
using gene profiling techniques– Luminal, HER2, basal
BRCA1 = breast cancer 1, early onset.BRCA2 = breast cancer 2, early onset.ER+ = estrogen receptor positive.PR+ = progesterone receptor positive.Trastuzumab [prescribing information]. South San Francisco, CA: Genentech, Inc; 2006
Breast Cancer Subtypes by Gene Profiling
• Normal-like
• Luminal-like– A– B
• ERBB2
• Basal-like
Good prognosisER+
Bad prognosis
ER+ or ER-
ER-, PR-, HER2-
ER- = estrogen receptor negative; ERBB2 = v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian); PR - = progesterone receptor positive.Pegram et al. Cancer Treat Res. 2000;103:57. Romond et al. N Engl J Med. 2005; 353:1673.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology™; 2006.Goldhirsch et al. 2005.
Prognostic Factors
Risk factors of BC recurrence:
• Tumor size
• Nodal status
• Grade
• Hormone receptor status
• Age of patient (35 yo)
• HER2/neu oncogene overexpression
Recent Development Timeline: Breast Cancer Chemotherapy
• Before anthracyclines– CMF, CMFVP
• With anthracyclines– Combinations: AC, FAC, AVCMF, FEC, CEF– Sequence and alternating– Dose intensity, dose density, HDCT
• Taxanes (paclitaxel/docetaxel)– Sequential monotherapy– Combinations– Biologic modifiers (trastuzumab, bevacizumab)– Integration in chemotherapy strategies
1970s1970s
1980s1980s
1990s1990s
2000 +2000 +AC = doxorubicin/cyclophosphamide; AVCMF = doxorubicin, vincristine, cyclophosphamide, methotrexate, and fluorouracil; CEF = cyclophosphamide, epirubicin, and fluorouracil; CMF = cyclophosphamide, methotrexate, and fluorouracil; CMFVP = cyclophosphamide, methotrexate, fluorouracil, vincristine, and prednisone; FAC = fluorouracil, doxorubicin, and cyclophosphamide; FEC = flourouracil, epirubicin, and cyclophosphamide; HDCT = high-dose chemotherapy with stem-cell support.Giordano SH et al. Cancer. 2004;100:44-52.
Hematologic Toxicities and Management
• Neutropenia: most common hematologic toxicity
• ASCO guidelines 2006 for prophylactic CSFs strategic guide– CSFs reserved for patients considered at high risk for FN
defined as ≥20% risk, or special circumstances—bone marrow compromise
– Or after a documented occurrence of FN or prolonged period of neutropenia in an earlier cycle of chemotherapy
• Especially if excessive dose reductions or delay in chemo
ASCO = American Society of Clinical Oncology.CSF = colony stimulating factor.FN = febrile neutropenia.ASCO. ASCO Guidelines. http://www.asco.org. Accessed December 31, 2006.
Overview
• Introduction to EBC
• Taxanes in HER2 Overexpressing Breast Cancer
• Symptom Management and Patient Support Strategies– Hematological Toxicities– Nonhematological Toxicities:
• Chemotherapy induced sensory peripheral neuropathy, fatigue, alopecia, arthralgia/myalgia, hypersensitivity reactions, nausea and vomiting, mucositis, and cardiac dysfunction
NonhematologicPeripheral Neurotoxicity
• Caused by peripheral neurodegeneration– Damage to sensory axons and myelin sheath
• Presents with loss of sensation—may progress to weakness and motor changes– Numbness, tingling, or burning pain
• Most distal to medial axon effects
– Bilateral, stocking-glove distribution
– Can be cumulative
– Short and long term symptoms
Wickham R. Clini J Oncol Nurs. 2007;11: 361-376.
Diagnostic StrategiesChemotherapy Induced NeuropathyTest Comments
Assessment of symptoms and clinical examination
Inter- and intra- observer variation
Vibration threshold Simple, non-invasive, and easily repeated but less sensitive than a clinical assessment
Monofilament test
Jebsen test of hand function
Grooved Pegboard test
Overall evaluation of neurologic function
Needs valuation in chemotherapy-induced neuropathy
Nerve conduction study
Needle electromyography
Objective evidence of neuropathy
Needs more study for sensitivity and specificity
Lee JJ, Swain SM. J Clin Oncol. 2006;24:1633-1642.
Careful Assessment and History
• Assess factors increasing risk, mobility, self-care, and fine-motor skill abilities – Careful history, writing, buttoning; functional impairment of
ADLs – Accurate assessment is key to decision making regarding dose
modifications, length of administration time, and discontinuation
• Teach patients to report any change in status – Numbness, burning, and/or tingling of extremities– “Overadherence” issue
• Manage pain– PT, OT, and/or medications
ADL = activity of daily living; OT = occupational therapy; PT = physical therapy.
Wickham R. Clini J Oncol Nurs. 2007;11:361-376.
Arthralgia/Myalgia
• Incidence – Docetaxel 10%– Paclitaxel 8%– Nab-paclitaxel 7%– Ixabepilone 8%
• Occurs few days post treatment with resolution in 2–6 days
– Shoulder and paraspinal muscles commonly affected
– Prophylactic or treatment analgesics such as ibuprofen, acetaminophen, or narcotics
Wickham R. Clin J Oncol Nurs. 2007;11:361-376. Perez EA et al. J Clin Oncol. 2007;25:3407-3414.Paclitaxel protein-bound [prescribing information]. Schaumburg, IL: American Pharmaceutical Partners, Inc; 2005.Icabepilone [prescribing information]. Princeton, NJ: Bristol Myers Squibb Company; 2007.
Fatigue
• Reported as one of the most problematic side effects over time related to treatment for BC– Adds to the severity of other symptoms of chemotherapy
– Diminishing quality of life, ability to manage self-care
• Symptoms may include– Lethargy—weakness or total lack of energy, malaise
– Sleeplessness
– Anxiety
– Difficulty with concentration, thinking clearly, making decisions
– Muscle pain, other constitutional symptoms
National Comprehensive Cancer Network. Cancer-Related Fatigue Guidelines. http://www.cancersymptoms.org/peripheralneuropathy/overview. Accessed December 31, 2006.
Fatigue
NCCN: Cancer-related fatigue guidelines • Treatment algorithm to identify and treat
fatigue • Patients evaluated using a brief screening
instrument • Evaluate level of distress• Assess if fatigue is interfering with daily
activities or functioning
National Comprehensive Cancer Network. Cancer-Related Fatigue Guidelines. http://www.cancersymptoms.org/peripheralneuropathy/overview. Accessed December 31, 2006.
Fatigue
• Additional interventions that help alleviate fatigue– Correct known causes of fatigue
• Anemia, nutritional deficits, sleep disorders
– Encourage regular exercise– Assess current medications
• Pain, antidepressant and anti-anxiety
– Other lifestyle modifications• Attention-restoring activities
– Psychological counseling – Physical therapy
National Comprehensive Cancer Network. Cancer-Related Fatigue Guidelines. http://www.cancersymptoms.org/peripheralneuropathy/overview. Accessed December 31, 2006.
Hypersensitivity Reactions • Occur in response to antigens that trigger antibody production:
Infrequent but potentially serious reactions • Characterized by facial flush, pruritis, rash, dyspnea with bronchospasm,
and hypotension
• Pre-medication:
• Availability of hypersensitivity reaction guidelines/protocol at infusion site
• Appropriate equipment and medications – epinephrine, corticosteriods, antihistamines, bronchodilators
Paclitaxel, Docetaxel Dexamethasone, Oral/IV H1 and H2 blockers
Docetaxel Additional Dexamethasone premed, Dexamethasone, Oral/IV H1 and H2 blockers
Nab-paclitaxel None (No solvent)
Ixabepilone Oral/IV H1 and H2 blockers (↓ Total dose of Cremophor EL)
Perez EA et al. J Clin Oncol. 2007;25:3407-3414.Docetaxel [prescribing information]. Bridgewater, NJ: Sanofi-Aventis, LLC; 2007.Icabepilone [prescribing information]. Princeton, NJ: Bristol Myers Squibb Company; 2007.Paclitaxel protein-bound [prescribing information]. Schaumburg, IL: American Pharmaceutical Partners, Inc; 2005.
Nausea and Vomiting Common Toxicity Criteria v 3
Adverse Event
Nausea Vomiting
Grade 1 Loss of appetite without alteration in eating habits
1 episode in 24 hrs
Grade 2 Oral intake decreased without significant weight loss,
dehydration or malnutrition; IV fluids indicated <24 hrs
2–5 episodes in 24 hrs; IV fluids indicated <24 hrs
Grade 3 Inadequate oral caloric or fluid intake; IV fluids, tube feedings, or
TPN indicated >24 hrs
≥6 episodes in 24 hrs; IV fluids, or TPN indicated
≥24 hrs
Grade 4 Life-threatening
consequencesLife-threatening
consequences
Grade 5 Death Death
IV = intravenous; TPN = total parenteral nutrition.
Mucositis
• Cause: Destroyed cell proliferation throughout GI tract
• Interventions– Good oral hygiene and soft toothbrush– Soda mouthwash– Adequate fluid intake– Treat with magic mouthwash p.r.n.
Cardiac Monitoring
• Thorough baseline cardiac assessment, – Including history, physical examination, and
assessment of LVEF by echocardiogram or MUGA scan
• Frequent monitoring for left ventricular function during and after trastuzumab treatment
• More frequent monitoring should be employed if treatment is withheld in patients who develop significant left ventricular cardiac dysfunction
LVEF = left ventricular ejection fraction.MUGA = multigated acquisition.
Patient Teaching
• Create environment in which patients are likely to report symptoms– Promote self-care measures
• www.cancersymptoms.org• www.cancersupportivecare.com• www.chemocare.com• www.canceradocacy.org
Wickham R. Clin J Oncol Nurs. 2007;11:361-376. Armstrong, 2005,ONF
Educational Considerations
• Teaching patients to manage the effects of treatment is demonstrated to decrease symptom distress
• Oncology nursing role to provide the education needed to assist patients in performing effective self-care