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