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Management of Adverse Effects of Taxane Therapy:
Focus on Neutropenia
Brenda K. Shelton, MS, RN, CRN, AOCNClinical Nurse Specialist
The Sidney Kimmel Comprehensive Cancer
Center at Johns Hopkins
Baltimore, MD
Myelosuppression in Taxane Therapy: More Facts
• Docetaxel produces more myelosuppression than paclitaxel
• Myelosuppression is exacerbated by coadministration of other myelosuppressive therapies– Most significant when administered with doxorubicin,
cyclophosphamide– Cisplatin and carboplatin are also contributors to hematologic
toxicity• Neutropenia is not more severe when taxanes are
delivered in conjunction with radiation• Most important determining factor for severity
of neutropenia is prior myelotoxic therapy
Nirenberg A et al. Oncol Nurs Forum. 2006;33:1193-1201.Markman. Support Care Cancer. 2003;11:144-147.Gligorov, Lotz. Oncologist.. 2004;9:3-8.
Classification of Neutropenia Reflects Clinical Risk
National Cancer Institute, 1999.
Slight(<2000)
Minimal(<1500)
Moderate(<1000)
Severe(<500)
Grade 1 Grade 2 Grade 3 Grade 4
Increased Risk of Febrile Neutropenia
• Pre-existing neutropenia• Past history of neutropenia
with other antineoplastic therapies
• Concurrent radiation• Bone marrow involvement with
disease• Advanced malignancy• Advanced age• Female sex• Poor performance status
• Comorbid health conditions– Chronic obstructive
pulmonary disease– Diabetes mellitus– Heart disease– Hepatic disease– Renal insufficiency
• Malnutrition (serum albumin level <3.0 mg/dL)
• Open wounds/tissue infection
Klastersky J. Clin Infect Dis. 2004;39:S32-S37.Nirenberg A et al. Oncol Nurs Forum. 2006;33:1193-1201.
Infections in Patients Receiving Taxanes
• Infection incidence: 20% to 26% of patients receiving taxanes
• Most common infections are urinary tract, upper respiratory, pneumonia, and sepsis
• Neutropenic enterocolitis has been specifically associated with taxanes
Evidence-Based Management of Myelosuppression
• Reduce severity or longevity of myelosuppression with hematopoietic growth factors as primary prophylaxis
• Infection prevention strategies• Aggressive diagnostic evaluation of fever• Empiric broad-spectrum antimicrobial therapy
with infectious signs or symptoms
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology™: Prevention and Treatment of Cancer-related Infections, Version 2.2007. http://www.nccn.org. Accessed October 2, 2007.
Hematopoietic Growth Factors
• Reduce severity and longevity of neutropenia• Clinical outcomes
– Reduced febrile neutropenia– Reduced number and length of hospitalizations for treatment of
febrile neutropenia– Decreased intravenous antibiotic use
• Indications– Therapy regimens with predicted incidence of neutropenia
20%– Past history of febrile neutropenia episodes– Age >65 years– Comorbid health conditions– Open wounds
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology™: Prevention and Treatment of Cancer-related Infections, Version 2.2007. http://www.nccn.org. Accessed October 2, 2007.
100.0
10.0
1.00.5
0.1
0.01
0 4 8 12 16 20 24Study day
Log ANC(x10-9/liter)
Start Filgratism/placebo Filgratism, n = 101Placebo, n = 110
Severe neutropenia (ANC <500)
Median ANC during cycle 1,CAE chemotherapy in small-cell lung cancer
ANC = absolute neutrophil count, CAE = cyclophosphamide, adriamycin, and etoposide. Crawford et al. N Engl J Med. 1991;325:164-170.
Filgrastim Decreases Severity and Duration of Chemotherapy-Induced Neutropenia
Evidence-Based Practice: Prevention of Neutropenia-Related Infections
• Environmental interventions– HEPA filtration– Private rooms– Cohorting patients
• Patient care strategies– Hygiene– Single-patient-use items– Aseptic techniques
• Prophylactic antimicrobials– With predicted prolonged
or severe neutropenia– Against defined pathogens
• Modifications in daily living– Exposure to others who are
potentially contagious– Immunizations– Dietary modifications– Hobbies and lifestyle
precautions (eg, gardening, animals)
HEPA = high efficiency particulate air.Larson E et al. Oncol Nurs Forum. 2004;31:717-723.National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology™: Prevention and Treatment of Cancer-related Infections, Version 2.2007. http://www.nccn.org. Accessed October 2, 2007.Nirenberg A et al. Oncol Nurs Forum. 2006;33:1202-1208. Zitella LJ et al. Clin J Oncol Nurs. 2006;10:739-750.
Evidence-Based Practice: Assessment in Patients With Neutropenia
• General standards– Overall state of health and symptoms– Pain locations and associated symptoms may signal infection– Assess common sites of infection—urine clarity, breath sounds, oral
mucosa– Vital signs—fever or subnormal temperature, tachycardia, tachypnea,
hypotension• Definition of fever
– 38.0ºC (100.1ºF) twice at least 2 hours apart– 38.2ºC (100.4ºF) at any time
• Diagnostic evaluation of fever– Blood cultures—2 sets, with at least 1 set drawn peripherally– Culture excrement—urine, stool, sputum, draining wounds– Culture lines
Friese CR. Semin Oncol Nurs. 2007;23:174-183.Klastersky J. Clin Infect Dis. 2004;39:S32-S37.National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology™: Prevention and Treatment of Cancer-related Infections, Version 2.2007. http://www.nccn.org. Accessed October 2, 2007.
Treatment of Febrile Neutropenia: Broad-spectrum Antimicrobial Therapy
Febrile with
validated or
presumed neutropenia
Broad-spectrum cephalosporin
and aminoglycoside
ORFluoroquinolone
ORCarbapenem
Vancomycin addedif potential line infection
Consider changing to
another antibacterial
regimenOR
Cover atypicalswith macrolide,
sulfa agent, clindamycin
Consideradding
antifungal
Consideraddingantiviral
Consider changes in antimicrobials every
72 hours if patient remains febrile
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology™: Prevention and Treatment of Cancer-related Infections, Version 2.2007. http://www.nccn.org. Accessed October 2, 2007.