2. Management of Adverse Effects of Taxane Therapy: Focus on Neutropenia Brenda K. Shelton, MS, RN, CRN, AOCN Clinical Nurse Specialist The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, MD

3. 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.

4. Classification of Neutropenia Reflects Clinical Risk National Cancer Institute, 1999. Slight (<2000) Minimal (<1500) Moderate (<1000) Severe (<500) Grade 1Grade 2Grade 3Grade 4

5. 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.

6. 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

7. 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.

8. 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.

9. 100.0 10.0 1.0 0.5 0.1 0.01 04 812 1620 24 Study day Log ANC (x10 -9 /liter) Start Filgratism/placebo Filgratism, n = 101 Placebo, 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

10. 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.

11. 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.

12. Treatment of Febrile Neutropenia: Broad- spectrum Antimicrobial Therapy Febrile with validated or presumed neutropenia Broad-spectrum cephalosporin and aminoglycoside OR Fluoroquinolone OR Carbapenem Vancomycin added if potential line infection Consider changing to another antibacterial regimen OR Cover atypicals with macrolide, sulfa agent, clindamycin Consider adding antifungal Consider adding antiviral 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.