Clinical 17
Pharmacy Practice News • December 2009
Educational Review Table 9. ASCO Recommendations on Use of CSFs As primary prophylaxis of febrile neutropenia for patients at high risk based on age, medical history, disease characteristics, and risk for myelotoxicity associated with a chemotherapy regimen.
Table 10. NCCN Recommendations on CSFs For Febrile Neutropenia
For patients undergoing nonmyelosuppressive therapy but who have risk factors for febrile neutropenia or infectious complications due to bone marrow compromise or other comorbidities. As secondary prophylaxis in patients who have previously experienced an episode of febrile neutropenia (without primary prophylaxis) when a reduction in dose of chemotherapy is not appropriate. Use can be considered as adjunctive treatment of febrile neutropenia for patients at high-risk for infectious complications.
Risk for Febrile Neutropenia
Use of CSF
High (>20%)
CSF
Intermediate May be (10%-20%) considered
To allow for a modest to moderate increase in dose-density and dose-intensity of chemotherapy regimens.
Low (<10%)
No CSFa
CSF
CSF
May be considered
May be considered
No CSF
No CSF
As an adjunct to progenitor-cell transplantation. For reduction of neutropenia in patients with AML with initial or repeat induction chemotherapy or completion of consolidation therapy. To increase ANC in patients with myelodysplastic syndrome. Following completion of initial induction therapy or first post-remission course of chemotherapy for ALL.
a
Only consider CSF if a patient is at significant risk for serious medical consequences of febrile neutropenia, including death. CSFs, colony-stimulating factors; NCCN, National Comprehensive Cancer Network Based on reference 9.
For limited use with refractory or relapsed AML (data suggest only a few shortened days of neutropenia can be expected). As prophylaxis in patients 65 y and older with diffuse aggressive lymphoma undergoing CHOP or more aggressive regimens. For patients being treated with lethal doses of total body radiotherapy. For pediatric patients, CSFs can be used for primary prophylaxis and as secondary prophylaxis or as adjunctive therapy for high-risk patients; the risk for secondary myeloid leukemia or myelodysplastic syndrome should be considered in children with ALL. ALL, acute lymphocytic leukemia; AML, acute myeloid leukemia; ANC, absolute neutrophil count; ASCO, American Society of Clinical Oncology; CHOP, cyclophosphamide, doxorubicin, vincristine, and prednisone; CSFs, colony-stimulating factors
Conclusion Febrile neutropenia remains a significant source of morbidity and mortality for patients receiving chemotherapy. Risk factors and models have been evaluated to aid in determining which patients may be at high risk for complications and which patients may be at low risk and therefore benefit from treatment with more cost-effective and convenient medication regimens. The IDSA and NCCN have developed guidelines for the prevention and treatment of infections associated with febrile neutropenia. In addition, the NCCN and ASCO have published guidelines regarding the appropriate
8. Lyman G. Risks and consequences of chemotherapyinduced neutropenia. Clin Cornerstone. 2006;8(suppl 5): S12-S18, PMID: 17379159. 9. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Myeloid growth factors (v.1.2009). http://www.nccn.org/professionals/physician_gls/PDF/ myeloid_growth.pdf. Accessed November 11, 2009. 10. Ellis M. Febrile neutropenia. Ann NY Acad Sci. 2008;1138:329-350, PMID: 18837909. 11. Lyman GH. Risk assessment in oncology clinical practice. From risk factors to risk models. Oncology (Williston Park). 2003;17(suppl 11):8-13, PMID: 14682113.
Based on reference 16.
they experienced a previous neutropenic complication in the immediate previous cycle with no plan to reduce the dose intensity of the chemotherapy regimen. When deciding if CSFs should be used, clinicians are encouraged to consider the intent of the chemotherapy regimen. For example, is therapy curative or is it being used for symptom control? For patients in the intermediate-risk category (10%-20%), NCCN recommends that if the risk is based on patient-specific factors, then use of CSFs is reasonable. However, if the intermediate risk is based on the chemotherapy regimen, then use of less myelosuppressive therapies or a dose reduction should be considered.
its management. Cancer. 2004;100(2):228-237, PMID: 14716755.
use of myeloid growth factors for this condition. Appropriate therapy in selected patients can significantly improve outcomes and reduce complications of febrile neutropenia.
References 1.
Lyman G. Kuderer NM. Epidemiology of febrile neutropenia. Support Cancer Ther. 2003;1(1):23-35, PMID: 18628128.
2. Viscoli C, Vanier O, Machetti M. Infections in patients with febrile neutropenia: epidemiology, microbiology, and risk stratification. Clin Infect Dis. 2005;40(suppl 4):S240-S245, PMID: 15768329. 3. McCabe WR, Jackson GG. Gram-negative bacteremia. II. Clinical, laboratory, and therapeutic observations. Arch Intern Med. 1962;110(6):856-864. 4. Wisplinghoff H, Seifert H, Wenzel RP, Edmond MB. Current trends in the epidemiology of nosocomial bloodstream infections in patients with hematological malignancies and solid neoplasms in hospitals in the United States. Clin Infect Dis. 2003;36(9):1103-1110, PMID: 12715303. 5. Hughes WT, Armstrong D, Bodey GP, et al. 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis. 2002;34(6):730-751, PMID: 11850858. 6. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Prevention and treatment of cancer-related Infections (v.2.2009). http://www.nccn.org/ professionals/physician_gls/PDF/infections.pdf. Accessed November 10, 2009. 7. Crawford J, Dale DC, Lyman GH. Chemotherapy-induced neutropenia: risks, consequences, and new directions for
12. Lyman GH, Lyman CH, Agboola O, for the ANC study group. Risk models for predicting chemotherapy-induced neutropenia. Oncologist. 2005;10(6):427-437, PMID: 15967836. 13. Klastersky J, Paesmans M, Rubenstein EB, et al. The Multinational Association for Supportive Care in Cancer risk index: a multinational scoring system for identifying low-risk febrile neutropenic cancer patients. J Clin Oncol. 2000;18(16):3038-3051, PMID: 10944139. 14. Walji N, Chan AK, Peake DR. Common acute oncological emergencies: diagnosis, investigation, and management. Postgrad Med J. 2008;84(994):418-427, PMID: 18832403. 15. Adelberg DE, Bishop MR. Emergencies related to cancer chemotherapy and hematopoietic stem cell transplantation. Emerg Med Clin N Am. 2009;27(2):311-331, PMID: 1947314. 16. Smith TJ, Khatcheressian J, Lyman GH, et al. 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol. 2006;24(19):3187-3205, PMID: 16682719. 17. Neupogen [package insert]. Thousand Oaks, CA: Amgen; 2007. 18. Neulasta [package insert]. Thousand Oaks, CA: Amgen; 2008. 19. Leukine [package insert]. Seattle, WA: Bayer; 2008. 20. Bohlius J, Herbst C, Reiser M, Schwarzer G, Engert A. Granulopoiesis-stimulating factors to prevent adverse effects in the treatment of malignant lymphoma. Cochrane Database Syst Rev. 2008;(4):CD003189, PMID: 18843642. 21. Sung L, Nathan PC, Alibhai SM, Tomlinson GA, Beyene J. Meta-analysis: effect of prophylactic hematopoietic colonystimulating factors on mortality and outcomes of infection. Ann Intern Med. 2007;147(6):400-411, PMID: 17876022.