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Monday, January 14, 2013

ONLINE FIRST: New Guideline from ASCO on Management of Neutropenia and Fever Aims to Reduce Unnecessary Hospitalizations



The American Society of Clinical Oncology has issued a new evidenced-based clinical practice guideline to help oncologists determine which of their adult cancer patients who have neutropenia with or without fever are at low risk of complications and can be safely managed at home. ASCO also endorsed a related guideline for children developed by the International Pediatric Fever and Neutropenia Guideline Panel--the first evidence-based guideline that specifically addresses the management of febrile neutropenia in children with cancer.


The new guideline comes at a difficult U.S. economic time when the high cost of health care is a major part of ongoing federal budget concerns. While Congress passed 11th hour legislation to avert the so-called fiscal cliff and delay cuts to Medicare, this action is temporary. Topics for ASCO clinical practice guidelines are selected in part on the basis of “significant clinical or economic importance,” the society notes.


The new guideline – which is based on 47 articles from 43 scientific studies – aligns with its “Top Five” list (OT, 6/25/12 and 1/10/13) of opportunities to improve the quality and value of cancer care by reducing the use of common tests and treatments that are not supported by clinical evidence (this list was developed through ASCO’s participation in the Choosing Wisely campaign launched by nine founding medical specialty societies and the American Board of Internal Medicine Foundation). A 2006 ASCO guideline on colony-stimulating factors recommended against their use for low-risk cancer patients with a less than 20 percent risk of febrile neutropenia; the new guideline endorses that 2006 recommendation.


Hospitalizations for febrile neutropenia in cancer patients are expensive, and they also put these patients at risk of hospital-acquired infections. Thus, outcomes can be better if patients who don’t need to be hospitalized are kept out of the hospital, according to the guideline.


“A priority of this evidence-based guideline was to help doctors identify patients with febrile neutropenia who do not need to be hospitalized,” said the co-chair of the new guideline panel, Christopher Flowers, MD, MS, Associate Professor of Pediatrics and Hematology and Medical Oncology at Emory University School of Medicine. “This guideline will help spare select patients from the discomfort and risks of hospitalization, such as exposure to treatment-resistant microbes, and has the potential to save substantial resources.”


As the number of adult cancer patients undergoing treatment continues to rise with the aging of the population, the number of febrile neutropenia patients will also rise -- “making it important to quantify the costs of treating this condition accurately and comprehensively,” according to a Canadian study on the direct medical costs of hospitalizations for febrile neutropenia published in Cancer (2010;116:742-748). This study of 46 patients with chemotherapy-induced febrile neutropenia found that the mean length of hospital stay per episode was 6.8 ± 4.9 days, and the mean overall cost per episode was $6,324 ± $4,783 in 2007 Canadian dollars.


The main driver of cost was length of stay in the hospital. Of particular interest is that the majority of patients in this study were classified as low risk.



The new ASCO guideline recommends the following for adult cancer patients:

            1. Prevention of infection for cancer patients with neutropenia without fever: Use of preventive treatment with antibacterial and antifungal drugs is recommended only for patients with profound neutropenia that will last for more than seven days, unless other factors increase the risk of complications. According to ASCO, “Overuse of preventive regimens contributes to the development of treatment resistant strains of microbes.”

The preferred preventive drugs for those with profound neutropenia who do need them are an oral fluoroquinolone for bacteria and an oral triazole for fungi, according to the guideline.

“Patients who don’t have a fever and have very low absolute neutrophil counts (less than 100 per microliter for more than seven days) can also be managed safely at home with oral antibiotics and antifungals to prevent infection,” said the other co-chair of the panel, Scott Ramsey, MD, PhD, Professor of Medicine at the University of Washington School of Medicine.

            2. Treatment of patients who have neutropenia with fever: Patients with neutropenia who develop a fever should go immediately to the physician’s office, outpatient clinic, or hospital to receive initial antibacterial treatment.

            3. Assessment of risk for complications in patients with febrile neutropenia using the well-validated MASCC (Multinational Association for Supportive Care in Cancer) score system or Talcott’s Rules. According to the new guideline, patients who are at lowest risk of complications have a MASCC score greater than 21 and fall into the Talcott’s Group 4. However, the guideline points out that its scientific literature review showed that medical complications occurred in up to 11 percent of febrile neutropenia patients who were identified by these assessment methods as being low risk.

            4. Management of febrile neutropenia at home: The guideline states that a subset of patients who have been assessed as at low risk for medical complications and other risk factors specified in the guideline can be managed safely at home with oral antibacterial and antifungal regimens after they have received the initial treatment in the physician’s office, clinic, or hospital. The guideline stresses that outpatient home management of febrile neutropenia is appropriate only for patients who can comply with frequent clinic visits; live within one hour or less than 30 miles from a hospital; have a caretaker present at home 24 hours a day; have 24-hour a day access to a telephone; and have transportation to get to the hospital, should that be necessary. Patients who experience a clinical worsening of their condition, organ dysfunction, or certain comorbid conditions should be managed in the hospital.

            5. Medications for management of febrile neutropenia at home: The guideline states that because fever in a patient with neutropenia is assumed to be due to bacterial infection, the first treatment should be with oral antibacterial drugs, typically a fluoroquinolone antibiotic plus amoxicillin/clavulanate. The guideline notes that these drugs are prescribed when there is a fever but the physician does not yet know the cause of the infection. Intravenous antibiotics given in the hospital are recommended for patients who are at high risk of complications.


The pediatric guideline for febrile neutropenia which ASCO endorsed was developed by the International Pediatric Fever and Neutropenia Guideline Panel, which was composed of experts in pediatric oncology and infectious disease as well as patient advocates. That guideline gives recommendations related to diagnosis, ongoing management, and initial antifungal and antibacterial treatment of febrile neutropenia in children with cancer and/or those undergoing blood stem-cell transplantation. The authors adapted evidence-based data from the adult population to the pediatric population as well as relying on evidence from clinical trials in children. This pediatric guideline was published in the Dec. 10 issue of the Journal of Clinical Oncology (2012;30:4427-4438).


Additional information about the new guideline, as well as related clinical tools and resources, are available at