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.