Treatment Of Febrile Neutropenia Research Articles

Costs Associated with Febrile Neutropenia in the US

Febrile neutropenia (FN) is a potentially life-threatening condition that may develop in cancer patients treated with myelosuppressive chemotherapy and result in considerable costs. This study was designed to estimate US healthcare utilization and costs in those experiencing FN by location of care, tumour type and mortality. Cancer patients who received chemotherapy between 2001 and 2006 were identified from the HealthCore Integrated Research Database®, a longitudinal claims database with enrolment, medical, prescription and mortality information covering 12 health plans and more than 20 million US patients. Patients who experienced FN were prospectively matched using propensity score methods within each tumour type of interest (non-Hodgkin's lymphoma, breast, lung, colorectal and ovarian cancer) to those not experiencing FN. Health resource utilization was compared per patient per month for unique prescriptions and visits (inpatient and outpatient) over the length of follow-up. Healthcare total paid costs adjusted to 2009 US dollars per patient per month were examined by FN group (FN vs non-FN, FN died vs FN survived), by source of care (physician office visit, outpatient services, hospitalization and prescriptions) and by tumour type. The number of unique FN-related encounters (inpatient and outpatient) and the number of patients experiencing at least one FN-related encounter were examined. The costs per encounter were tabulated. FN encounters differ from FN episodes in that a single FN episode may include multiple FN encounters (i.e. a patient is seen multiple times [encounters] for treatment of a single FN event [episode]). A total of 5990 patients each were successfully matched between the FN and non-FN (control) groups. Health resource utilization was generally higher in those with FN than in controls. FN patients incurred greater costs (mean ± SD: $US9628 ± 12 517 per patient-month) than non-FN patients ($US8478 ± 12 978). Chemotherapy comprised the majority of costs for both FN (33.5%) and non-FN (40.6%) patients. The largest cost difference by categorical source of care was for hospitalization (p < 0.001). FN patients who died had the highest mean total costs compared with FN surviving patients ($US21 214 ± 25 596 per patient-month vs $US8227 ± 8850, respectively). Follow-up time for those surviving was, on average, 6.6 months longer. Hospitalization accounted for 53.1% of costs in those experiencing mortality with FN, while chemotherapy accounted for the majority of costs (37.1%) in surviving FN patients. A total of 6574 patients with at least one FN encounter experienced a total of 55 726 unique FN-related encounters, 90% of which were outpatient in nature. The majority of FN-related encounters (79%) occurred during the first chemotherapy course. The average costs for FN encounters were highest for inpatient encounters, $US22 086 ± 43 407, compared with $US985 ± 1677 for outpatient encounters. The occurrence of FN in cancer patients receiving chemotherapy results in greater healthcare resource utilization and costs, with FN patients who die accounting for the greatest healthcare costs. Most FN patients experience at least one outpatient FN encounter, and the total cost of treatment for FN continues to be high.

Deviations from guideline-based therapy for febrile neutropenia in cancer patients.

6078 Background: Febrile neutropenia (FN) is a common cause of morbidity in cancer patients. We examined guideline and non-guideline based care for cancer patients hospitalized with FN and examined how treatment influenced outcomes. Methods: The Perspective database was used to examine the treatment of solid tumor patients with FN from 2000-2010. To capture initial decision-making, we examined treatment within 48 hrs of admission. Based on evidence-based guidelines we determined the appropriate use of guideline-based antibiotics as well as use of treatments not routinely recommended, vancomycin and granulocyte-colony stimulating factors (GCSF). Hierarchical mixed effects models were developed to examine the influence of patient, physician, and hospital characteristics on the quality of treatment. Patients were stratified into low and high-risk groups and the effect of initial treatment on outcome (nursing home discharge and death) examined. Results: Among 25,231 patients with FN, within 48 hours of admission blood cultures were obtained in 90%, guideline-based antibiotic administered to 79%, vancomycin to 37%, and GCSF to 63%. Patients treated at high-volume hospitals, by high-volume physicians and patients managed by hospitalists were more likely to receive guideline-based antibiotics (p&lt;0.05). Vancomycin use increased with time from 17% in 2000 to 55% in 2010 while GCSF use only decreased from 73% to 55%. Patients treated by internists and hospitalists were more likely to receive vancomycin; high-volume physicians were less likely to treat with both vancomycin and GCSF (p&lt;0.05). Among patients who received GCSF, 15% received only one dose and 22% received 2 doses of filgrastim. Among low-risk patients prompt initiation of guideline-based antibiotics decreased the risk of discharge to a nursing facility (OR=0.78; 95% CI, 0.66-0.91) and death (OR=0.65; 95% CI, 0.50-0.85). Conclusions: There is substantial variability in the initial treatment for FN in cancer patients. While use of appropriate empiric antibiotics is high, use of non guideline-based treatments such as vancomycin and GCSF are common. Physician and hospital factors are the most important predictors of both guideline and non guideline-based treatment.

Aztreonam and Vancomycin Use for Episodes of Febrile Neutropenia During Hematopoetic Stem Cell Transplantation

The spectrum of bacterial infections seen during febrile neutropenia(FN) in HSCT recipients continues to change, especially with the emergence of multi-drug resistant organisms. Aztreonam(AZ) plus Vancomycin (VAN) have been used successfully for FN in cancer patients, however the effectiveness of AZ plus VAN for FN during HSCT is largely unknown. A retrospective chart review was performed to determine the effectiveness of AZ in FN. 822 consecutive HSCT patient charts were reviewed(2004-2008). All patients received a minimum of 48hours of AZ/VAN treatment for FN. Patients had received ciprofloxacin as prophylaxis. The criteria for success was based upon evidence based guidelines for the evaluation of new anti-infective drugs in FN FN(CID Vol.15 Nov 1992 Suppl: 206-15) as follows:1.Unexplained fever: defervesence within 72hr without recurrence and no clinical s/s infection.2.Clinically defined infection: Clinical improvement including fever, without antibiotic change or death3.Microbiologically defined infection: All s/s and microbiological evidence of disease eradicated without recurrence for 7days. 67 AZ treated patients were identified. Demographics: age = 59(24-77), gender male = 29, Diagnosis: myeloma = 48, NHL = 10, AML = 7, HSCT type: autologous = 45. allogeneic = 22. Median time to start AZ(post-HSCT infusion): day +8(-6-12), Number of AZ treatment days = 6(2-33) Treatment Outcome1.Unexplained fever(n = 36): Success = 26/36(73%), 2 patients died2.Clinically defined(n = 12): Hospital Pneumonia(n = 9): Success = 5/9(55%-ATB changes), Typhlitis (n = 1) 0/1 (ATB change), Cellulitis(n = 1)(0/1success (ATB change)3.Microbiologically defined infection (see Table 1): 20 patients experienced 30 episodes of microbiologically confirmed infection. The majority (80%) were gram positive cocci blood stream infections and were successfully treated (80%-2 died). Gram negative BS infection overall success was 50%(1died) 6 patients developed clinical CDAD and 9 patients became VRE surveillance positive shortly after AZ treatment. A non-significant trend towards more BS infections was seen in allo-HSCT recipients(p = 0.086) AZ/VAN was effective in preventing breakthrough infections for patients with unexplained fever, but less effective for patients with documented infections, requiring change or addition of antibiotics. These results are comparable to those seen in non-HSCT cancer patients with FN(Bodey et al.Cancer 1996 Apr1 77(7)).Table 1Microbiologically Defined InfectionOrganismSourceSuccessful Outcome(%)Strept Viridansblood (n = 11)91 (1 died-polymicrobial)CONS(2 positive cx's at 2sitesblood (n = 5)80 (changed atb)Entereococcus Faecalisblood (n = 4)75 (1died-polymicrobial)MSSAblood (n = 2)50 (1 died-polymicrobialE.Coliblood = 1/urine = 1BS-1 died//Urine = successEnterobacterurine (n = 1)100Burkholderiablood = 10 ( died-polymicrobial)C.Diffstool (n = 3)66 (1 died-polymicrobial) Open table in a new tab

A systematic review and meta-analysis of anti-pseudomonal penicillins and carbapenems in pediatric febrile neutropenia

Carbapenems represent a broad-spectrum alternative to anti-pseudomonal penicillin (APP) combination or single-agent therapy for the management of pediatric febrile neutropenia (FN). Our primary objective was to describe the risk of treatment failure in children treated with an APP or carbapenem as initial empiric treatment for FN. Our secondary objective was to compare outcomes of APP versus carbapenem therapy in this population. An electronic search of Ovid Medline, EMBASE, and the Cochrane Central Register of Controlled Trials was performed. We limited studies to prospective pediatric trials of FN in which at least one treatment arm consisted of an APP (with or without an aminoglycoside) or a carbapenem. Of 7,281 articles reviewed, 27 studies comprising 30 treatment regimens were included for meta-analysis. Treatment failure, including antibiotic modification, occurred in 41% (95% confidence interval (CI) 32-50%), 34% (95% CI 27-41%), and 35% (95% CI 24-45%) of patients treated with APP-aminoglycoside, APP monotherapy, and carbapenem monotherapy regimens, respectively. There was no significant difference in treatment failure including antibiotic modification, infection-related mortality, or adverse events when comparing either APP regimen with carbapenem monotherapy. Although a limited number of studies were available, when stratified by FN risk group, no differences were seen in any outcome. Our meta-analysis suggests that APP-aminoglycoside, APP monotherapy, and carbapenem monotherapy are all efficacious therapeutic options for the empiric management of pediatric FN.

Single-Agent, Broad-Spectrum Fluoroquinolones for the Outpatient Treatment of Low-Risk Febrile Neutropenia

To evaluate the use of oral, single-agent, broad-spectrum fluoroquinolones in the treatment of low-risk febrile neutropenia (FN). MEDLINE via Ovid (1948 to May, week 3, 2011) and EMBASE (1980 to 2011, week 21) were searched using the terms febrile neutropenia, fluoroquinolone, quinolone derivative, levofloxacin, moxifloxacin, and neoplasm. References of selected articles, review articles, and treatment guidelines were reviewed. Trials evaluating the efficacy of oral, single-agent, broad-spectrum fluoroquinolones in the treatment of chemotherapy-induced FN were included if the majority of patients in the study had low-risk FN. Trials involving pediatric patients, non-Food and Drug Administration-approved fluoroquinolones, or monotherapy with ciprofloxacin or ofloxacin were excluded. Data extracted included study design, patient demographics, antiinfective regimens, and treatment outcomes. Four clinical trials were included. One trial compared levofloxacin with piperacillin/tazobactam with a success rate (afebrile at 72 hours) of 76.5% in the levofloxacin group compared with 88.3% in the piperacillin/tazobactam group. This trial was not limited to low-risk patients. The remaining 3 trials investigated moxifloxacin monotherapy in low-risk patients. Two of these were noncontrolled trials with success rates (afebrile at 5 days) of 91% and 95%. The final trial randomized patients to moxifloxacin or ceftriaxone and had success rates (hospital discharge at 48 hours) of 79.2% and 73.9%, respectively. In all 4 trials, treatment of FN with levofloxacin or moxifloxacin was deemed to be safe and effective. Although all studies had positive results, they were limited by small sample sizes and the absence of universal use of control comparisons. Use of oral, single-agent, broad-spectrum fluoroquinolones for outpatient treatment of FN in low-risk patients has shown promising results. At this time, this type of therapy should be limited to low-risk patients. Future clinical trials should include larger sample sizes and a comparison with existing first-line oral therapy-oral ciprofloxacin plus amoxicillin/clavulanate.

Factors influencing patient preferences for outpatient treatment of febrile neutropenia.

6041 Background: Febrile neutropenia (FN) is a serious hematologic toxicity of cancer chemotherapy. Studies show that patients at low risk for FN complications can be treated safely and effectively at home instead of in hospital. The objective of this study was to evaluate factors affecting patient preferences for outpatient treatment of FN using a discrete choice experiment (DCE). Methods: We asked patients with non-Hodgkin lymphoma undergoing chemotherapy to complete a self-administered DCE questionnaire based on the following attributes: out-of-pocket costs (levels: $10, $25, $50, $100); unpaid caregiver time required daily (levels: 1 hour, 2 hours, 4 hours, 8 hours); and probability of return to hospital (levels: 5%, 10%, 20%, 50%). Using these attributes, we generated sets of paired scenarios based on an orthogonal main effects plan. Ten paired scenarios were included in the final questionnaire. For each pair, we asked participants to select the scenario they preferred, to assess how they traded off between attributes. We analyzed results using logistic regression. Results: Seventy-eight patients completed the questionnaire. The mean age of participants was 59.6 years (range: 23.7 - 87.2 years) and 46 (59%) were male. Eleven patients (14%) had been previously hospitalized for treatment of FN. Six hundred and ten paired scenarios were included in the analysis. The regression coefficients for all three attributes were statistically significant (p<0.01), indicating that they all influence the willingness of patients to accept outpatient FN therapy. For every $20 increase in out-of-pocket costs the adjusted odds ratio (OR) of accepting outpatient care was 0.84 (95% CI: 0.77, 0.91); for every 1 hour increase in unpaid caregiver time required daily the adjusted OR was 0.92 (95% CI: 0.87, 0.97); and for every 10% increase in probability of return to hospital the adjusted OR was 0.49 (95% CI: 0.45, 0.53). Conclusions: Out-of-pocket costs, unpaid caregiver time required, and probability of return to hospital all significantly influence patients’ willingness to accept outpatient treatment of FN. Healthcare decision makers could use this information to design and implement programs for delivery of outpatient care for FN.

Prophylactic and therapeutic strategies in chemotherapy-induced neutropenia

Introduction: Neutropenia poses a serious threat to patients on chemotherapy. It exposes them to the risk of infection – including potentially fatal infections – and also leads to delays in treatment and reductions in dose intensity, which can compromise the possibility of a favorable outcome.Areas covered: The use of granulocyte colony-stimulating factors (G-CSF) and antibiotics to prevent febrile neutropenia (FN) and to ameliorate cancer chemotherapy-induced myelosuppression is discussed, based on a systematic search of Pubmed for clinical trials, reviews and meta-analysis published in the last 20 years. We consider that the treatment of FN, with the emphasis on careful attention to the patient, prompts antibiotic therapy and good hospital care.Expert opinion: We would argue that antibiotic prophylaxis should be offered routinely to patients receiving cytotoxic chemotherapy for acute leukemia and for patients with solid tumors and lymphoma receiving high-dose chemotherapy. In patients undergoing cyclical standard-dose myelosuppressive chemotherapy, we believe that prophylaxis is indicated during the first cycle of chemotherapy in which there is an expectation of grade 4 neutropenia (< 500 neutrophils). However, although the use of antibiotics and haematopoietic growth factors may improve quality of life by reducing the risk and consequences of FN, further study of the magnitude of their effects is needed.

Historical Cohort Study of the Efficacy and Safety of Piperacillin/Tazobactam Versus Fourth-Generation Cephalosporins for Empirical Treatment of Febrile Neutropenia in Patients with Hematological Malignancies

We retrospectively evaluated the efficacy and safety of the combination drug piperacillin/tazobactam (PIPC/TAZ) in comparison with those of fourth-generation cephalosporins (4th Cephs) as initial empirical treatment in hematological malignancies patients with febrile neutropenia (FN). Among 200 patients assessed in this study, 49 had received PIPC/TAZ and 151 4th Cephs. Patient background characteristics were comparable between the two treatment groups. The overall efficacy rate in those receiving 4th Cephs and PIPC/TAZ was 57.0% (86/151 patients) and 59.2% (29/49 patients), respectively, with no significant difference detected between the two treatment regimens (P = 0.78). Treat-ment did not need to be discontinued or interrupted due to development of adverse drug reactions in any of the patients. Therefore in this study the efficacy and safety of PIPC/TAZ as initial antimicrobial treatment for FN in patients with hematological malignancies were not inferior to those of 4th Cephs. Based on the preliminary data obtained in this study, we propose to conduct a multicenter, prospective, controlled study to compare PIPC/TAZ versus CFPM given as empirical antimicrobial treatment against FN in patients with hematological malignancies.

Underreporting of Myelotoxicity with Emerging Regimens for Selected Hematologic Malignancies

AbstractAbstract 1501 Background:Clinical data guiding colony-stimulating factor (CSF) use with emerging regimens that incorporate targeted agents for treating hematologic malignancies are not readily available, even though many of these regimens can produce increased myelosuppressive side-effects. This review assessed the diligence of reporting around neutropenia, febrile neutropenia (FN), and neutropenic complications as well as the use of CSF and antibiotics in published clinical trials evaluating emerging regimens for the treatment of non-Hodgkin lymphoma (NHL), Hodgkin lymphoma, multiple myeloma (MM), or chronic lymphocytic leukemia (CLL). Methods:English-language reports of randomized controlled phase 3 studies of the selected hematologic malignancies published between January 2005 and June 2009 were identified by searching Medline, EMBASE, and Cochrane databases. Publications that met the inclusion criteria were retrieved and data on the incidence of neutropenia and its complications and CSF/antibiotic use were extracted. The percentage of publications that reported each outcome was then calculated. Results:Fifty seven trials that met the criteria were included in this analysis. Overall, 68% of trials reported on the incidence of grade 3/4 neutropenia (80%, MM; 71% CLL; 63% NHL, and 50%, Hodgkin lymphoma). However, fewer trials (18%) reported on the incidence of FN (57%, CLL; 20%, MM; 8%, NHL; and 0%, Hodgkin lymphoma). Similarly, only a few trials (4%) reported neutropenia-related hospitalizations (8%, NHL; 0% each for Hodgkin lymphoma, MM, and CLL). Primary prophylactic use of CSF was defined in the methods section of 19% of trials and CSF use was reported in the results section of 25% of trials. Use of antibiotics for FN treatment was defined in the methods section of 2% of trials and was reported in the results section of 9% of trials. Conclusion:In the published phase 3 studies evaluated in this analysis, clinically significant neutropenia and neutropenia-related events (including FN) were poorly or generally not described. Furthermore, the use of CSF and antibiotics was infrequently and inconsistently reported in the published literature of emerging regimens. A standardized approach to reporting neutropenic outcomes and the related use of supportive care measures can assist clinicians to prospectively manage the relevant toxicities associated with emerging regimens for hematologic malignancies. This is essential for the safe and effective transition of these regimens into broad clinical practice. Disclosures:Gregory:Amgen Inc.: Consultancy; Astellas: Research Funding; Celgene: Research Funding; Cephalon: Research Funding, Speakers Bureau; Genentech (Roche): Consultancy, Research Funding, Speakers Bureau; GlaxoSmithKline: Research Funding; Immunomedics: Research Funding; NCIC CTG: Research Funding; Novartis: Consultancy, Research Funding; Onyx: Research Funding; Spectrum Pharmaceuticals: Consultancy. Abella:Amgen Inc.: Employment, Equity Ownership. Moore:Amgen Inc.: Consultancy, Honoraria.

Clinical efficacy and safety of cefepime in febrile neutropenic patients with lung cancer

Fever often occurs along with chemotherapy-induced neutropenia. This condition is referred to as febrile neutropenia (FN). Excellent guidelines for FN treatment have recently been published; however, there has so far been insufficient research concerning FN associated with solid tumors, especially in Japan. A multi-institution prospective study of cefepime for the treatment of FN in lung cancer patients was conducted. The objective of this study was to determine the efficacy and safety of cefepime for FN in lung cancer patients. Cefepime (2 g x 2/day) was administered to patients with FN after treatment for lung cancer. The therapeutic response rate, the effect of the drug on pathogen populations, and the incidence of adverse effects were statistically analyzed. Twenty-one patients with FN were registered for this study. One case was excluded because of protocol violation; therefore, a total of 20 cases were analyzed. Three days after the administration of cefepime, improvement was evident in 15 cases. The response rate was 75%, 95% CI: 53.1-88.8. After 7 days, 17 patients experienced improvement in their condition (85%, 95% CI: 64.0-94.8). Carbapenem was eventually substituted for cefepime in three cases, and all cases finally displayed improvement. There was no mortality. Pathogens for FN were detected in three cases and they disappeared in one case. Four patients experienced adverse side effects, including skin eruption, serum bilirubin elevation, neutrophil depletion, and anterior chest pain. There were no severe adverse events. In this study, cefepime demonstrated a high degree of clinical efficacy and safety in the treatment of FN. Empiric monotherapy using cefepime is a recommended regimen for FN in patients with lung cancer in Japan.

Evaluation of direct medical costs of hospitalization for febrile neutropenia

Treatment of febrile neutropenia (FN) is costly, because it typically involves hospitalization. As cancer rates continue to increase, the number of patients suffering from FN will also increase, making it important to quantify the costs of treating this condition accurately and comprehensively. A consecutive sample of patients admitted to an inpatient hematology/oncology ward at a tertiary care hospital for the treatment of chemotherapy-induced FN was enrolled in this study. Patients were followed prospectively during hospitalization, and information on medical resource utilization including length of stay, medications, and laboratory and diagnostic tests was collected. Costs, extracted from hospital and provincial databases, were used to calculate the overall cost per FN episode, from the hospital perspective. Fifty-one episodes of FN that occurred in 46 patients were included in the study. Approximately 52% of these episodes occurred in women, and 65% of these episodes occurred in patients with hematologic malignancies. The mean +/- standard deviation age of patients was 60.3 +/- 13.4 years. The mean length of stay per episode was 6.8 +/- 4.9 days. The mean overall cost per episode was 6324 +/- 4783 in 2007 Canadian dollars. Hospitalization for the treatment of FN is expensive. The results of this study could be used in future economic evaluations of preventive measures and treatments for FN, including primary prophylactic administration of hematopoietic growth factors and outpatient treatment of this condition.

Management of infection in patients with acute leukemia during chemotherapy in Japan: questionnaire analysis by the Japan Adult Leukemia Study Group

Guidelines for the management of febrile neutropenia (FN), deep fungal infection or use of granulocyte colony-stimulating factor (G-CSF) published in the US and Europe cannot be directly applied in other countries. In this study, we undertook a questionnaire survey of member institutions of the Japan Adult Leukemia Study Group to investigate the status of, and problems with, the management of infectious complications in patients with acute leukemia. The questionnaire consisted of 52 multiple-choice questions covering therapeutic environment, antibacterial, and antifungal prophylaxis, empirical therapy (ET) for FN, and use of G-CSF. The results were compared to a previous survey performed in 2001. Usable responses were received from 134 of 184 (71.7%) institutions. With regard to antibacterial prophylaxis, fluoroquinolones and sulfamethoxazole-trimethoprim were most commonly used. Regarding antifungal prophylaxis, the most frequently used agent was fluconazole, followed by itraconazole. In ET for FN, monotherapy with cephems or carbapenems accounted for almost all of the responses. Most respondents indicated that they used micafungin (MCFG) in ET. Prophylactic use of G-CSF during remission induction therapy in acute myeloid leukemia was reported by only 4% of respondents. Strategies for antibacterial and antifungal prophylaxis or treatment of FN should be reviewed and updated as needed.

Prospective study comparing hospital costs and DRG reimbursement of inpatient treatment of febrile neutropenia during adjuvant anthracycline-based CTX for primary breast cancer

e11570 Background: Febrile neutropenia (FN) is an undesired effect of myelosuppressive chemotherapy (CTX). To date limited data on costs of FN management is available. We compared costs and reimbursement of FN in a study of BC patients during adjuvant anthracycline (AC)-based CTX. Methods: Prospective, observational, longitudinal study in primary BC patients, enrolled 1–12/2006 consecutively before start of CTX in a German university clinic. FN was defined as fever &gt;38ºC + ANC &lt;1x109/L. Clinical and resource use data + DRG reimbursement were analyzed from medical charts. Costs for inpatient therapy of FN were compared to DRG reimbursement and results are presented from provider's perspective. Results: Of all patients approached (n=61), n=54 signed informed consent (88.5%), n=2 withdraw (3.3%) and n=2 were excluded from evaluation because of non-AC-based CTX. Patients were on avg. 57.4 (32–74) years and otherwise healthy ECOG 1 (n=50; 100%). Tumor classification was T1 n=25, T2 n=19, ≥T3 n=5 and pTx n=1. Chemo regimen was either AC-based n=29 (58.0%) or AC+taxane-based n=21 (42.0%). 12 episodes of FN occurred (24.0%) in 11 patients, one patient had 2 episodes; n=11 were treated as inpatients, n=1 as outpatient. Hospital stay for inpatients was on avg. 5.4 days (4–8), 0.7 days below average according to G-DRG catalog. Mean cost per FN episode requiring hospital treatment was 1.827 €, SD ±795 € (95%CI: 1293, 2361). Basic hospital costs were 83%, drug treatment 9% and diagnostics 8% of total direct costs. DRG reimbursement for inpatient FN was 2.145 € per episode, thus cost covering for the provider. Avg. reimbursement rate/day was 417 € (253–665 €). Inadequately DRG coding (n=4) resulted in a loss of 1.069 €/case (-42.2%). Conclusions: Costs for FN treatment vary among patients and DRG reimbursement does not necessarily reflect providers’ costs. Main cost drivers are hospitalization, length of stay, diagnostics and antibiotics. Surprisingly, inpatient treatment of FN under current therapy regimen is cost covering if adequately coded. This prospective evaluation and calculation of provider's costs and reimbursement helps understanding the allocation of resources for rational and cost-covering therapy. [Table: see text]

Comprehensiveness of Quality of Life Instruments in Capturing Concerns Related to Chemotherapy-Induced Neutropenia

Neutropenia is a serious hematologic consequence of cancer chemotherapy that can lead to further complications such as febrile neutropenia (FN). FN is potentially life threatening and often requires hospitalization. Few studies have evaluated the impact of neutropenia on quality of life (QoL). This study quantified QoL using two nonneutropenia-specific instruments, the EQ-5D questionnaire, a generic tool used to measure health-related QoL, and the Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire, and a neutropenia-specific instrument, the Functional Assessment of Cancer Therapy - Neutropenia (FACT-N) questionnaire. The FACT-G is a 27-item questionnaire that examines QoL in patients with cancer using four subscales. A neutropenia-specific subscale (NSS) has been developed for use with the FACT-G; this combined questionnaire is the FACT-N. Data were collected from patients, who provided informed consent, and who were admitted to Sunnybrook Health Sciences Centre, Toronto, Canada, for the treatment of chemotherapy-induced FN. Linear regression models were fitted to examine the relationship of scores from the neutropenia-specific instrument with those obtained from the other instruments. Two models were fitted using the NSS as the response variable. Predictors for the regression models were the FACT-G scores for each of the subscales (physical, emotional, social and functional wellbeing) and the five domains of the EQ-5D (mobility, self-care, usual activity, pain/discomfort and anxiety/depression) along with the visual analog scale (VAS) component of this tool. The physical and emotional wellbeing subscales of the FACT-G had a strong relationship to the NSS (p < 0.05); the social and functional well-being subscales had a much weaker relationship (p > 0.5). For the EQ-5D, the pain/discomfort domain had the strongest relationship to the NSS (p=0.18); the remaining domains, with or without the VAS, all demonstrated a weaker relationship (p > 0.5). Model fit was assessed by the adjusted R2 statistic; it was 0.54 when FACT-G subscales were used as the predictors compared to −0.04 for the EQ-5D domains indicating that the FACT-G was a better predictor of neutropenia-related concerns. Neutropenia concerns appear to be more closely related to cancer specific QoL compared to general quality of life as demonstrated by the stronger relationship of the NSS to the FACT-G than to the EQ-5D. This may be due to the comprehensiveness of the FACT-G questionnaire where a possible score anywhere from 0 to 24 or 28 can be obtained in each of the subscales, compared to three-point descriptive system for each of the domains of the EQ-5D.

Physical Examination Can Predict the Risk of Infection in Patients with Febrile Neutropenia (FN)

Purpose In patients with febrile neutropenia (FN) who undergo chemotherapy, it is not common that the infection focus can be accurately diagnosed and a pathogen identified. In the initial phase of standard treatment for FN, the CDC guidelines specify administration of broad-spectrum antibiotics. However, these antibiotics should be de-escalated as soon as the pathogen and infection focus are identified. In order to evaluate an infection focus, we must first hear from the patients about their conditions and carry out careful physical examinations. Therefore, we studied the contribution of physical examinations to the identification of infection focus in patients of FN.Method We included patients who were admitted to the Division of Blood and Stem cell transplantation, Shizuoka Cancer Center Hospital, between February 2006 and July 2006, for treatment of hematological malignancies. We reviewed all events in patients whose axillary temperature reached 38.0 °C or higher during their chemotherapy courses. We studied the following items: the number of leukocytes and neutrophils at onset, duration of fever, concomitant catheter use, prophylactic antibiotics, regimen of empirical treatment, isolated pathogen, infection focus, mortality and the cause of death. We treated cases of continuous fever of 38.0 °C or higher as a single set of events. If the temperature fell below 38.0 °C and then returned to 38.0 °C or higher after a period of 48 hours or longer, we treated the second occurrence as a new case. The findings of physical examinations were classified into the following 4 categories: oral site, respiratory site, gastrointestinal site, and skin site (if any, including the portion of catheter insertion). The true infection focus was determined depending on the results of culture, otherwise, with reference to the patient's clinical course. Criteria for decision of infection are below:a positive result of culture from an aseptic site,identification of a pathogen that can explain the patient's clinical symptoms, orclinical course suggesting an infection supported by clinical examination or imaging.Non-infectious diseases were diagnosed by clinical information and categorized as tumor fever, allergic reaction or unknown fever.Results Overall, 85 FN episodes were observed. Patient characteristics included a median age of 56 years (range: 26–86) and a M:F ratio of 37:48. Of the 85 cases, there were 22 cases of acute myelogeneous leukemia, 16 acute lymphoblastic leukemia, 29 malignant lymphoma, 12 multiple myeloma and 6 others. The maximum degree of fever was 38.0–38.9°C in 68 cases (80%), 39.0–39.9°C in 13 cases (15%), and more than 40.0°C in 4 cases (5%). We detected at least one site of infectious focus in 63 cases (74.1%). The sites included 34 oral, 26 respiratory, 20 gastrointestinal and 11 skin. In some cases, infectious symptoms appeared in multiple sites; 2 sites in 15 cases, 3 in 2 cases and 4 in 5 cases. Of the 85 cases, the final diagnosis was infection in 17 cases (20%), tumor fever in 11 cases (13%), allergic reaction in 8 cases (9%) and unknown in 49 cases (58%). Among the 17 cases of infection, we were able to predict the infectious focus in 11. Multivariate analysis showed significant correlations between diagnosis of infection and three factors: first FN in treatment course (P=0.0021), bacterial prophylaxis (P=0.0054) and infectious findings of skin site (P=0.059, marginal).Conclusion Detailed physical examinations enable early and advance diagnosis of infection in cases of FN during chemotherapy.

Evaluation of hospitalization costs for treatment of febrile neutropenia (FN)

17549 Background: FNis a common, serious adverse effect of chemotherapy; treatment is costly as it typically involves hospitalisation, use of intravenous antibiotics, and occasionally hematopoietic growth factors (CSFs). Several studies have evaluated direct medical costs of hospitalisation for FN; no Canadian studies detailing the costs associated with modern treatment protocols are available. Methods: A consecutive sample of patients admitted to an inpatient hematology/oncology ward at a tertiary care hospital (Sunnybrook Health Sciences Centre in Toronto, Canada) was enrolled in this study. The inclusion criteria were: 1) diagnosis of chemotherapy-induced FN upon admission and 2) ≥ 18 years of age at time of admission. Patients were followed prospectively during hospitalization and information on medical resource utilization, including length of stay, medications, laboratory and diagnostic tests, was collected. Costs, extracted from hospital and provincial databases, were used to calculate the overall cost, in 2007 Canadian dollars (CAD), per FN episode, from the hospital perspective. Results: Fifty-one episodes of FN occurred in 46 patients; 75% of episodes were classified as low risk based the Multinational Association of Supportive Care in Cancer (MASCC) risk score model. Fifty-one percent of episodes occurred in females and 65% of episodes occurred in patients with hematologic malignancies. Mean ± SD age of patients was 60.3 ± 13.4 years. CSFs were used in 29% of the episodes. The mean length of stay per episode was 6.8 ± 4.9 days. The mean costs of antibiotics and CSFs were 258 ± 413CAD and 354 ± 721CAD, respectively. The mean overall cost per episode was 5800 ± 4275CAD. Conclusions: Hospitalization for the treatment of FN is expensive. Future work will evaluate cost-effectiveness of alternative treatment models for FN, such as outpatient treatment or early hospital discharge programs for low risk episodes, and prophylactic interventions such as the use of CSFs. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen Canada Amgen Canada

Carbapenems versus other beta-lactams in treating severe infections in intensive care: a systematic review of randomised controlled trials

Carbapenems have not been comprehensively compared in clinical trials with fourth-generation cephalosporins (4GC) and antipseudomonal penicillins (APP) in the treatment of severe infections (SI) and febrile neutropenia (FN). A systematic review of CENTRAL, EMBASE, MEDLINE and JICST-EPlus for randomised controlled trials was conducted to establish the currently available evidence. Database searching was supplemented by hand searching and contacting conference organisers. Searching was completed in November 2006 and no restriction was placed on the language of publication. Data were extracted on clinical response, bacteriologic response, all-cause mortality and adverse events. Of the 265 papers identified, 12 were appropriate for meta-analysis (four 4GC and eight APP). The results showed that carbapenems are associated with a significant reduction in all-cause mortality (relative risk 0.62, 95% confidence interval: 0.41 to 0.95; p=0.03) compared to APP in the treatment of SI, and withdrawals due to adverse events (RR 0.65, 95% CI: 0.45 to 0.96; p=0.03) are also less common. When compared in the treatment of FN, carbapenems are associated with a significant increase in clinical response during the initial 72 h of treatment (RR 1.37, 95% CI: 1.09 to 1.74; p=0.008) and bacteriologic response (RR 1.73, 95% CI: 1.03 to 2.89; p=0.04). For all other outcomes, including all comparisons with 4GC, there were no significant differences between treatments. The use of carbapenems rather than APP could reduce mortality and, by simplifying treatment decisions, reduce the time before patients receive appropriate antibiotic treatment. The currently available evidence is insufficient for distinguishing between carbapenems and 4GC.

Invasive respiratory Aspergillosis is a treatable disease with early diagnosis and aggressive therapy

19632 Background: Invasive respiratory aspergillosis (IRA) is a fulminant infection in immunocompromised hosts. This study aims to evaluate the effectiveness of early screening of patients and the outcome of them during febrile neutropenia (FNP) episodes. Methods: Between 2003 and 2006, 212 FNP episodes were evaluated and the cases who are still febrile at their fifth FNP treatment were screened with computerized tomography (CT) of sinus, thorax and and other relevant sites. Results: Fungal infection rate was 15%, while IRA was detected in 22 patients. Thirteen of these patients were male. Fifteen patients had hematological malignancies, 6 had solid tumors and one patient had combined immunodeficiency and hemophagocytic lymphohistiocytosis. All patients had absolute neutrophil count of zero for 5 to 30 days (median 11.5 days). IRA cases were classified as definite (n:3), probable (n:7) and possible (n:12) according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group. Amphotericin B was administered emprically to all cases and continued as a single agent in 7 patients. Variable modifications with caspofungin, voriconazole or itraconazole were done in 11, 9 and 2 patients, respectively. At present, 7 patients are disease-free after completion of treatment, 6 patients are still on antifungal therapy, 4 patients were lost despite antifungal therapy and 5 patients died of underlying disease while in remission or with stabile disease for a median of 339 days (range: 13–1027 days). Therefore, our remission rate and overall survival rates are 83% and 60% respectively. Conclusions: Contrary to the previous reports, we suggest that IRA is a treatable disease with early diagnosis and aggressive antifungal therapy and it is worthwhile to screen FNP patients who are resistant to wide-spectrum antibiotics with CT for early intervention. No significant financial relationships to disclose.

Safety and effectiveness of outpatient therapy in 596 low-risk patients with febrile neutropenia (FN)

8116 Background: Outpatient (Outpt) therapy was a major innovation in treatment of FN, but rapid adoption of this strategy precluded adequately powered clinical trials comparing Outpt with inpatient (Inpt) therapy. Among clinically eligible low-risk patients, non-medical barriers such as lack of a caregiver, mandate treatment in the Inpt setting. We compared the outcomes of low-risk pts with FN treated as Outpts to their low-risk counterparts who were treated as Inpts for non-medical reasons. Pts & Method: We selected 1 episode of FN at random for each of 596 consecutive low-risk pts. 103 pts with no caregiver or telephone at home, a history of non-compliance or residence >30 min from the hospital were treated initially as Inpts; 493 pts were treated initially as Outpts. We collected 6 outcomes from medical records: response to the initial antibiotic (abx) regimen, ultimate response (both defined as resolution of all signs and symptoms of infection), medical complications requiring treatment, and days of hospitalization, fever, and abx therapy. The Inpts and Outpts were similar in performance status, comorbidities, bacteremias, and pneumonias. There was a non-significant trend toward more mucositis in Inpts and they were older than Outpts. Confounding factors were strongly associated with outcomes. Thus, we compared Outpts’ outcomes with Inpts’ using logistic or linear regression (as appropriate) to adjust for these factors. Result: All Inpts and Outpts ultimately responded to abx therapy. After adjustment, there were no significant differences between Inpts’ and Outpts’ responses to initial abxs or rates of complications (Table). 19% of Outpts required hospitalization. Outpts’ mean length of stay was significantly shorter than those treated initially as Inpts. Conclusion: We found no evidence that Outpt therapy of FN in low-risk pts compromises effectiveness or safety. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration American Cancer Society, Bayer, Merck

Pegfilgrastim (Neulasta®) and Filgrastim (Neupogen®) Use in Patients Receiving Chemotherapy in Oncology Practices: Interim Results of the Assessment of Current CSF Evaluation for Proper Therapy (ACCEPT) Study.

Introduction: The pivotal trials of pegfilgrastim and filgrastim demonstrated their value as primary protection if initiated 24 hours after chemotherapy (CT) administration from CT cycle 1. Current clinical use patterns for pegfilgrastim and filgrastim may differ and may include primary protection in cycle (C) 1 or secondary protection in later cycles. Additionally, the initiation day within a CT cycle could be early (primary protection), late (reactive use), or for treatment of established neutropenia or febrile neutropenia (FN). A retrospective chart review is underway to determine current use patterns and applications of once-per-cycle pegfilgrastim (approved in 2002) and daily filgrastim.Methods: Patient (pt) medical records are being retrospectively collected from 100 randomly selected US private oncology practices. Eligible pts are ≥18 years of age, diagnosed with non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD), lung (LC), ovarian (OC), colorectal (CRC) or breast (BC) cancers, and have received ≥1 CT cycle. This planned interim analysis evaluates pegfilgrastim and filgrastim utilization in cancer pts receiving CT in 2003.Results: Medical records of 624 pts from 34 sites receiving pegfilgrastim or filgrastim have been abstracted to date. Pegfilgrastim was initiated in 351(56%) pts and filgrastim was initiated in 273 (44%) pts. Of the 624 pts, 120 (19%) received both pegfilgrastim and filgrastim (no pt used both products in the same cycle). Of these, 94 (78%) received pegfilgrastim after initially receiving filgrastim while 26 (22%) received filgrastim after initially receiving pegfilgrastim.The distribution of tumor types for the 325 pts receiving only pegfilgrastim was BC 43%; LC 24%; NHL 20%; HD 5%; OC 5%; CRC 3%. The planned CT cycle length (days) for pts receiving pegfilgrastim was: Q21 (56%), Q14 (11%), Q28 (11%), Q7 (2%). In C1, 58% of pts received pegfilgrastim; in C2, 86% received pegfilgrastim. In C1, pegfilgrastim was administered ≤3 days after CT in 76% (142/187) of pts and in 83% (200/240) of pts in C2. C1 use of pegfilgrastim was 68% for lymphoma and 54% for solid tumor pts.The distribution of tumor types for the 179 pts receiving only filgrastim was BC 46%; LC 24%; CRC 12%; NHL 9%; HD 6%; OC 4%. The planned CT cycle length (days) for pts receiving filgrastim was: Q21 (35%), Q28 (17%), Q14 (15%), Q7 (12%). In C1, 62% of pts received filgrastim; in C2, 83% received filgrastim. In C1, filgrastim was administered ≤3 days after CT in 31% (34/111) of pts increasing to 48% (52/108) of pts in C2. Filgrastim was initiated ≥10 days after CT in C1 in 48% (53/111) of pts and in 26% of pts (28/108) in C2. C1 use of filgrastim was 58% for lymphoma and 63% for solid tumor pts.Conclusions: From this interim analysis, most pts initiated pegfilgrastim in C1 and early within a cycle, suggesting primary protection. Most pts initiated filgrastim also in C1, however the day of initiation is much later, suggesting reactive use or treatment of established neutropenia or FN. Future analyses will evaluate factors associated with use (or non-use) of pegfilgrastim and filgrastim including baseline and treatment characteristics.