Incidence Of For Febrile Neutropenia Research Articles

Comparison of prophylactic effects for chemotherapy-induced neutropenia between same-day vs next-day administration of pegteograstim in chemotherapy regimen composed of day 1 intensive myelosuppressive agent: A randomized phase III trial (CONCISE, KCSG PC22-11).

TPS12149 Background: Administration of peg-GCSF 24 to 72 hours after chemotherapy is usually recommended. Next-day administration (after 24 hours) resulted in fewer duration of Gr4 chemotherapy-induced neutropenia (CIN) and decreased severity of CIN than same-day (within 4 hours). However, patients sometimes receive same-day Peg-GCSF for the sake of convenience. In addition, a few prior studies showed that the same-day method is comparable or superior to the next-day in preventing CIN, especially in regimens that include day 1 myelosuppressive agents. Thus, we aim to test hypothesis that same-day administration of pegteograstim, a new formulation of peg-GCSF, is non-inferior to next-day administration in terms of Gr4 CIN duration. Methods: This study is a randomized, multicenter, open-label, investigator-initiated phase 3 study. Patients with adjuvant/neoadjuvant or 1st palliative chemotherapy comprising intensively myleosuppressive agents on day 1 (mFOLFIRINOX, ECb, EP, FOLFIRI, and FOLFOX) are enrolled. The patients are assigned to the same-day arm or the next-day arm in a 1:1 ratio. Randomizations are stratified according to number of CIN risk (1 vs ≥2), setting (perioperative vs palliative), and interval (2- vs 3-week). In the same-day, pegteograstim 6 mg is SC injected within 4 hrs after chemotherapy, while 24-36 hrs in the next-day. CBC test is performed daily from day 5 to 9 during the cycle 1. From cycle 2 to 4, treatments are performed in accordance with general practice, including checking for febrile neutropenia (FN), dose intensity, and safety. The primary endpoint is duration of Gr4 CIN (during cycle 1), and secondary endpoints include incidence of Gr 3-4 CIN (cycle 1), severity of CIN (cycle 1), time to recovery ANC 1000/㎕ (cycle 1), incidence of FN, CIN-related dose delay, and dose intensity. In order to verify non-inferiority of 0.6 days of Gr4 CIN duration, we estimated a significance level of 5%, power of 80%, and drop-out rate of 15%. This results in the need for a total of 160 patients, 80 in each arm. We are currently recruiting patients (since Nov 2022). Clinical trial information: KCT0007694 .

The Impact of Baseline Risk Factors on the Incidence of Febrile Neutropenia in Breast Cancer Patients Receiving Chemotherapy with Pegfilgrastim Prophylaxis: A Real-World Data Analysis.

Background: There are sparse data addressing whether standard risk factors for febrile neutropenia (FN) are relevant in patients receiving myelosuppressive chemotherapy and primary prophylaxis for FN, which would have implications for variables to consider during real-world comparative analyses of FN incidence.Objective: To assess the impact of baseline patient-specific risk factors and regimen risk on the incidence of FN in patients receiving pegfilgrastim primary prophylaxis.Methods: This was a retrospective observational study in patients with breast cancer (BC) who received myelosuppressive chemotherapy and prophylactic pegfilgrastim identified January 1, 2017-May 31, 2018 from MarketScan® research databases. The outcomes were defined as incidence of FN in the first cycle and among all cycles of chemotherapy using three different definitions for FN. Logistic regression and generalized estimating equations models were used to compare outcomes among patients with and without patient-specific risk factors and among those receiving regimens categorized as high-, intermediate-, or other-risk for FN (low-risk or undefinable by clinical practice guidelines).Results: A total of 4460 patients were identified. In the first cycle of therapy, patients receiving intermediate-risk regimens were at up to 2 times higher risk for FN across all definitions than those receiving high-risk regimens (P<0.01). The odds ratio for main FN among patients with ≥4 versus 0 risk factors was 15.8 (95% confidence interval [CI]: 1.5, 169.4; P<0.01). Patients with ≥3 FN risk factors had significantly greater risks for FN across all cycles of treatment than those with no risk factors; this was true for all FN definitions.Discussion: The choice of FN definition significantly changed the impact of risk factors on the FN outcomes in our study, demonstrating the importance of evaluating all proxies for true FN events in a database study. This is particularly important during real-world study planning where potential missteps may lead to bias or confounding effects that render a study meaningless.Conclusions: In patients with BC receiving chemotherapy with pegfilgrastim prophylaxis, patient-specific risk factors and regimen risk levels are determinants of FN risk. In real-world studies evaluating FN incidence, it is imperative to consider and control for these risk factors when conducting comparative analyses.

The Impact of Baseline Risk Factors on the Incidence of Febrile Neutropenia in Breast Cancer Patients Receiving Chemotherapy with Pegfilgrastim Prophylaxis: A Real-World Data Analysis

Background: There are sparse data addressing whether standard risk factors for febrile neutropenia (FN) are relevant in patients receiving myelosuppressive chemotherapy and primary prophylaxis for FN, which would have implications for variables to consider during real-world comparative analyses of FN incidence. Objective: To assess the impact of baseline patient-specific risk factors and regimen risk on the incidence of FN in patients receiving pegfilgrastim primary prophylaxis. Methods: This was a retrospective observational study in patients with breast cancer (BC) who received myelosuppressive chemotherapy and prophylactic pegfilgrastim identified January 1, 2017-May 31, 2018 from MarketScan® research databases. The outcomes were defined as incidence of FN in the first cycle and among all cycles of chemotherapy using three different definitions for FN. Logistic regression and generalized estimating equations models were used to compare outcomes among patients with and without patient-specific risk factors and among those receiving regimens categorized as high-, intermediate-, or other-risk for FN (low-risk or undefinable by clinical practice guidelines). Results: A total of 4460 patients were identified. In the first cycle of therapy, patients receiving intermediate-risk regimens were at up to 2 times higher risk for FN across all definitions than those receiving high-risk regimens (P&lt;0.01). The odds ratio for main FN among patients with ≥4 versus 0 risk factors was 15.8 (95% confidence interval [CI]: 1.5, 169.4; P&lt;0.01). Patients with ≥3 FN risk factors had significantly greater risks for FN across all cycles of treatment than those with no risk factors; this was true for all FN definitions. Discussion: The choice of FN definition significantly changed the impact of risk factors on the FN outcomes in our study, demonstrating the importance of evaluating all proxies for true FN events in a database study. This is particularly important during real-world study planning where potential missteps may lead to bias or confounding effects that render a study meaningless. Conclusions: In patients with BC receiving chemotherapy with pegfilgrastim prophylaxis, patient-specific risk factors and regimen risk levels are determinants of FN risk. In real-world studies evaluating FN incidence, it is imperative to consider and control for these risk factors when conducting comparative analyses.

History of whole pelvis plus para-aortic radiation is a risk factor associated with febrile neutropenia during chemotherapy for recurrent cervical cancer.

Radiation-based therapy is widely used for advanced cervical cancer. Prior radiation-based therapy is a potential risk factor for febrile neutropenia (FN). However, the effect of irradiation field size on the incidence of FN during recurrent cervical cancer treatment is unclear. This study aimed to investigate the relationship between prior irradiation field size and FN development during recurrent chemotherapy. This retrospective, observational study included cervical cancer patients who received recurrent chemotherapy between November 2006 and June 2020. The patients were classified into two groups based on the area of irradiation fields. The first group included patients with a history of whole pelvis (WP) irradiation (WP group). The second group had patients who underwent WP plus para-aortic lymph node (PAN) irradiation (WP + PAN group). The incidences of hematological toxicities and FN during the recurrent chemoradiotherapy were compared between the two groups. The FN incidence was significantly higher in the WP + PAN group than in the WP group (32.1% vs. 0%, P < 0.001). The incidence of Grade 4 neutropenia was not significantly different between the WP + PAN and WP groups. The nadir absolute neutrophil counts were significantly lower and the dose reduction or discontinuation rate of chemotherapy was significantly higher in the WP + PAN group than in the WP group. History of WP plus PAN radiation is a risk factor for developing FN during recurrent cervical cancer chemotherapy.

Primary Prophylaxis of Febrile Neutropenia With Pegfilgrastim in Small-cell Lung Cancer Patients Receiving Amrubicin as Second-line Therapy.

We evaluated the efficacy of primary prophylaxis with pegfilgrastim (PEG) for febrile neutropenia (FN) in small cell lung cancer (SCLC) patients receiving amrubicin (AMR). A retrospective cohort study was conducted in patients with SCLC receiving AMR as second-line therapy. A total of 33 patients were treated with AMR (no PEG group), while 13 patients were treated with AMR plus prophylactic administration of PEG (PEG group). The severity of neutropenia was significantly reduced in the PEG group compared to the no PEG group (p=0.02). The incidence of FN in the no PEG and PEG groups was 27.3% and 7.7%, respectively. The time to development of FN tended to be longer in the PEG group compared to the no PEG group (p=0.132). Primary prophylaxis with PEG may be beneficial in reducing the risk of FN in patients with SCLC receiving AMR.

Real-world myeloid growth factor (MGF) prophylaxis patterns in patients receiving chemotherapy at intermediate-risk for febrile neutropenia (FN): A systematic review.

e24116 Background: Many patients receiving myelosuppressive chemotherapy are at an intermediate risk (10-20%) of developing FN. In this setting, clinical practice guidelines recommend an individualized approach towards MGF prophylaxis based on regimen and patient-specific FN risk factors. The purpose of this review is to summarize and describe the real-world MGF prophylaxis patterns, patient-specific risk factors, and FN outcomes in patients receiving chemotherapy at intermediate risk of FN. Methods: We searched the MEDLINE database (PubMed) for peer-reviewed published articles using the keywords “primary prophylaxis,” “febrile neutropenia,” and “intermediate risk” from 2000-2020. Articles were included if they were cohort or case control studies, and excluded if the data were derived from clinical trials. Studies from outside the United States or where the methods cannot be verified were also excluded. Results: Out of 131 studies identified, 7 met the inclusion/exclusion criteria after review. Most studies included adult cancer patients diagnosed with breast, lung or colorectal cancer receiving chemotherapy identified using public/private insurance claims or electronic medical records. In the 2000s, MGF prophylaxis rates were around 17-22% in patients receiving intermediate-risk regimens; while in 2010s, the prophylaxis rate increased to &gt; 50%. Patient-specific FN risk factors were prevalent, but MGF primary prophylaxis rates among those receiving intermediate risk regimens were generally low (around 24-28%); approximately 25% of patients with &gt; 1 FN risk factor received primary prophylaxis. Primary prophylaxis rates differed by tumor type; breast cancer had the highest rate (~46%), followed by non-small cell lung (~24%), and colorectal (~8%). FN incidence varied among patients with FN risk factors (~7 to 29%) across intermediate risk regimens, and the relative risk of FN (vs. those without risk factors) ranged from 1.1 to 2.2. Conclusions: Although historically low, MGF prophylaxis in patients receiving intermediate risk regimens has been increasing. Patient FN risk factors were widespread and associated with increased FN incidence. Since appropriate primary prophylaxis in patients at intermediate-risk could potentially improve population-based FN-related outcomes, future studies should focus on whether biosimilar MGFs as primary prophylaxis are cost-effective and could better optimize the care reflected in current MGF practice guidelines.

Clinical Impact of Primary Prophylactic Pegfilgrastim in Breast Cancer Patients Receiving Adjuvant Docetaxel-Doxorubicin-Cyclophosphamide Chemotherapy.

PurposeThe regimen including concurrent docetaxel, doxorubicin, and cyclophosphamide (TAC) has been categorized as an important risk factor for febrile neutropenia (FN). This comparative study examined the clinical impact of long-acting granulocyte colony-stimulating factor (G-CSF) (pegfilgrastim) during adjuvant TAC chemotherapy in Korean patients with advanced breast cancer.MethodsWe analyzed data from 239 patients who received 6 cycles of adjuvant TAC chemotherapy. We categorized patients into 2 groups according to the use of primary prophylactic pegfilgrastim and compared the incidence and risk of FN, hospital care costs, and survival in the 2 groups.ResultsThe incidence of FN decreased from 54.2% to 21.2% in all patients, after the use of pegfilgrastim. The analysis of a total of 1,432 chemotherapy cycles showed that the incidence of FN decreased from 36.1% to 9.1% after the use of pegfilgrastim. Moreover, the decrease in the incidence of FN with the use of pegfilgrastim resulted in a significant decrease in the mean duration of neutropenia (4.15 to 1.29 days), the risk of hospitalization (99.5% to 29.7%) and the mean total hospital care cost (USD 3,038 to USD 2,347). High relative dose intensity (RDI) in patients treated with pegfilgrastim than in those not treated with pegfilgrastim (99.18% vs. 93.85%) was associated with a better overall survival (p = 0.033).ConclusionsThe use of pegfilgrastim during adjuvant TAC chemotherapy was significantly associated with a decrease in the incidence and risk of FN, hospital care costs, and risk of death compared to the use of adjuvant TAC without primary prophylaxis.

Effectiveness of Prophylaxis with Granulocyte Colony-Stimulating Factor Among Cancer Patients Receiving Myelosuppressive Chemotherapy in US Clinical Practice

Introduction: Clinical practice guidelines recommend prophylaxis with granulocyte colony-stimulating factor (G-CSF) for most patients receiving chemotherapy with an intermediate risk or high risk for febrile neutropenia (FN). In real-world settings, however, many of these patients do not receive G-CSF prophylaxis, while other patients receiving low-risk or unclassified chemotherapy regimens receive G-CSF prophylaxis. Evidence on the effectiveness of G-CSF prophylaxis among diverse patient populations based on clinically rich data sources is currently limited. Methods: A retrospective cohort design and data from four US health systems-Henry Ford Health System, Kaiser Permanente Northwest, Reliant Medical Group, and Geisinger Health System-were employed. Data included patients' demographics and clinical profile, cancer, treatment, supportive care, and outcomes, and were compiled from electronic medical records systems, administrative data warehouses, medical charts, and cancer registries. The study population comprised all patients who received a course of myelosuppressive chemotherapy for breast cancer, colorectal cancer, lung cancer, or non-Hodgkin's lymphoma (NHL) from 2009-2017. For each patient, each cycle of chemotherapy during the course, and use of G-CSF primary/secondary prophylaxis and FN events in each cycle, were characterized and included as a separate observation in the analytic file; thus, each patient could contribute multiple chemotherapy cycles to the analysis. Odds ratios (OR) for FN in cycle 1 and all cycles, respectively, were estimated for patients who did versus did not receive G-CSF prophylaxis in the corresponding cycle, and odds ratios were adjusted for clustering (by patient and health system [i.e., across cycles]) as well as for differences in baseline characteristics between G-CSF prophylaxis groups using inverse probability of treatment weighting (IPTW). Results: The study population included 3,775 cancer chemotherapy patients who contributed 24,076 cycles of observation. The distribution of patients by cancer was: breast, 47%; lung, 26%; colorectal, 17%; and NHL, 10%; the distribution of patients by chemotherapy FN risk level was: high, 54%; intermediate, 12%; low, 15%; and unclassified, 19%. In cycle 1, 33% of patients received G-CSF prophylaxis (filgrastim, 53%; pegfilgrastim, 47%), and odds of FN in this subgroup were one-half those of patients who did not receive G-CSF prophylaxis (OR = 0.49 [0.35-0.67]) (Table). Across all cycles, 31% of patients received G-CSF prophylaxis (filgrastim, 55%; pegfilgrastim, 45%), and FN odds in these cycles were comparably reduced (OR = 0.76 [0.64-0.91]). Findings considering other model specifications, and across subgroups of the study population, were similar. Conclusions: In this retrospective evaluation of patients receiving myelosuppressive chemotherapy for breast cancer, colorectal cancer, lung cancer, or NHL in US clinical practice, about one-third of patients received G-CSF prophylaxis in cycle 1 and subsequent cycles, and FN incidence was significantly lower among patients who did (versus did not) receive G-CSF prophylaxis. These findings highlight the effectiveness of G-CSF prophylaxis in reducing FN risk across cycles of chemotherapy among a diverse population of cancer patients receiving myelosuppressive regimens. Disclosures Lamerato: National Cancer Institute, Centers for Disease Control and Prevention, Amgen Inc., AstraZeneca, Evidera, eMAX Health: Research Funding. Lyman:G1 Therapeutics, Halozyme Therapeutics, Partners Healthcare, Hexal, Bristol-Myers Squibb, Helsinn Therapeutics, Amgen Inc., Pfizer, Agendia, Genomic Health, Inc.: Consultancy; Amgen Inc.: Other: Research support, Research Funding; Janssen Scientific Affairs, LLC: Research Funding; Generex Biotechnology: Membership on an entity's Board of Directors or advisory committees. Kaur:Amgen Inc., Evidera, eMAX Health: Research Funding. Shah:Amgen Inc.: Employment, Equity Ownership. Lawrence:Amgen Inc.: Employment, Equity Ownership. Silvia:Amgen Inc.: Research Funding. Hanau:Amgen Inc.: Research Funding. Weycker:Amgen Inc.: Research Funding.

1591. Infectious Outcomes of Levofloxacin Prophylaxis in Obese vs. Non-obese Patients with Hematologic Malignancies

BackgroundLevofloxacin given at a standard dose of 500 mg daily is recommended for antibacterial prophylaxis in patients receiving myelosuppressive chemotherapy. Obese patients have been shown to exhibit enhanced clearance of levofloxacin and may be at risk for prophylactic failure.MethodsThis was a single-center, retrospective cohort study evaluating the infectious outcomes of obese (BMI >30 kg/m2) and non-obese (BMI ≤ 30 kg/m2) adult patients who received standard dose levofloxacin as primary prophylaxis after chemotherapy. Patients were included if they were treated at our institution from June 1, 2014 through May 31, 2017 and had National Comprehensive Cancer Network (NCCN) defined intermediate infection risk. Patients were excluded if they were lost to follow-up, treated at another institution for febrile neutropenia (FN), or had renal impairment (estimated creatinine clearance (CrCL) less than 50 mL/minute). The primary endpoint was incidence of FN as defined by NCCN guidelines. Secondary endpoints included 30-day mortality and the correlation between estimated levofloxacin AUC and rates of FN. Levofloxacin AUC was estimated from CrCL using the method of Pai et al.ResultsA total of 98 patients met the inclusion criteria (34 obese and 64 non-obese). Estimated CrCL was similar between obese and non-obese patients (mean 84.5 vs. 81.6 mL/minute, P = 0.61), as was estimated levofloxacin AUC (mean 115.1 mg hour/L vs. 107.8 mg hour/L, P = 0.25). FN occurred in 26 patients: 12 (35.3%) obese and 14 (21.9%) non-obese (P = 0.16). Bivariate comparisons between patients who did and did not experience FN found no significant associations with the weight-related variables total body weight (mean 84.7 vs. 82.0 kg, P = 0.56), BMI (mean 28.8 vs. 28.0 kg/m2, P = 0.51), or body surface area (1.99 vs. 1.96 m2, P = 0.62). Multivariate analysis identified presence of mucositis and diagnosis of multiple myeloma as variables independently associated with FN. No patients died within 30 days of the FN event.ConclusionThere were no significant associations between body weight-related variables and FN in this cohort of patients with similar renal function. Obesity should not be a justification for more aggressive levofloxacin dosing schemes when used for FN prophylaxis.Disclosures All authors: No reported disclosures.

Incidence and risk factors of febrile neutropenia in patients with non-Hodgkin B-cell lymphoma receiving R-CHOP in a single center in Japan

PurposeThe incidence of and risk factors for febrile neutropenia (FN) in Japanese non-Hodgkin B-cell lymphoma (B-NHL) patients receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and predonisolone (R-CHOP) chemotherapy are unknown. We conducted this study to address this issue.MethodsIn this single-center, retrospective, observational study, 466 patients with B-NHL who completed an R-CHOP regimen within a 7-year period and who planned to undergo at least three cycles of this regimen were analyzed. The following FN-related factors were assessed: fever, infection, disease state, neutrophil count, and prophylactic interventions such as use of antibiotics and/or granulocyte colony-stimulating factor (G-CSF). We simulated the FN incidence and 95% confidence interval (CI) of patients without prophylaxis with G-CSF (cycle 1) using bootstrap sampling.ResultsThe incidence of FN was 9.1% (42 of 462) in cycle 1 and 12.3% (57 of 462 patients) throughout all cycles, with 73.7% (42/57) developing FN during cycle 1. Risk factors for FN among patients with B-NHL treated with R-CHOP were albumin <35 g/L (p = 0.0047), relative dose intensity <85% (p = 0.0007), and lack of prophylaxis with G-CSF (p = 0.0006) in cycle 1. In the simulation analysis, the estimated FN incidence in cycle 1 was 16.2% (95% CI [10.9–22.2]).ConclusionsAt 9.1% in cycle 1 and 12.3% throughout all cycles, the incidence of FN was lower than previously reported, possibly reflecting the appropriate use of G-CSF in this clinical setting. For patients with risk factors, the prophylaxis with G-CSF may decrease the occurrence of FN.

Evaluation of the Use of Granulocyte Colony-Stimulating Factors (G-CSFs) for Neutropenia Primary Prophylaxis in Solid Tumors at a Tertiary Care Hospital, Retrospective Study

Objective: First, to determine the appropriate prescribing of granulocyte colony-stimulating factors (G-CSFs) for febrile neutropenia (FN) as primary prophylaxis during the first cycle of chemotherapy in breast, lung, gastric, esophageal, nasopharyngeal or colorectal cancer patients. Second, to compare the incidence of FN between patients who received G-CSF appropriately and inappropriately. Methods: This was a retrospective cohort study conducted at the Princess Norah bint Abdulrahman Al Faisal Oncology Center. We used cancer registry report which included adult patients with newly diagnosed solid tumors, such as breast, lung, gastric, esophageal, nasopharyngeal and colorectal cancer between January 2013 and December 2013. Patients were excluded if they did not receive chemotherapy after diagnosis and had renal or liver impairment. The appropriate indication of G-CSFs for FN primary prophylaxis was evaluated based on the National Comprehensive Cancer Network (NCCN) guidelines and published data. Results: G-CSFs were appropriately prescribed as primary prophylaxis in 85% of patients. The incidence of FN between the appropriate and inappropriate groups were not statistically significant (p=0.315). However, G-CSF use was inappropriate in 28 of the 29 patients who received chemotherapy regimens with high risk of developing FN; among these patients only three patients developed FN. Conclusion: The prescribing of G-CSFs for FN primary prophylaxis at our institution was found to be inappropriate on some occasions; mostly when G-CSFs were not prescribed with regimens associated with high risk of FN.

Incidence and Predictors of Febrile Neutropenia among Early-Stage Breast Cancer Patients Receiving Anthracycline-Based Chemotherapy in Korea

Objective: This retrospective study was undertaken to assess the incidence of and risk factors for febrile neutropenia (FN) during adjuvant chemotherapy for early-stage breast cancer (ESBC). Methods: A multicenter survey of three tertiary hospitals was conducted, with data extracted from the records of ESBC patients treated with adjuvant chemotherapy containing AC (doxorubicin, 60 mg/m² and cyclophosphamide, 600 mg/m² every 21 days). Assessments included clinical characteristics, chemotherapy dose modifications, and incidence of FN. Results: A total of 610 patients were included for analysis. The incidence of grade 4 neutropenia and FN was 44.6 and 8.5%, respectively. Reduced relative dose intensity (RDI) less than 85% occurred in 11.0% of patients, and there were treatment delays in 12.6% of patients. Multivariate analysis identified several independent predictors for FN, including the presence of grade 4 neutropenia and pretreatment calculated estimated glomerular filtration rate less than 60 ml/min. Conclusion: Patients with ESBC are at substantial risk for FN and reduced RDI when treated with adjuvant AC chemotherapy. Predictive models based on risk factors identified in this study should enable the selective application of supportive measures in an effort to deliver the full dose of chemotherapy.

Incidence of Febrile Neutropenia in Korean Female Breast Cancer Patients Receiving Preoperative or Postoperative Doxorubicin/Cyclophosphamide Followed by Docetaxel Chemotherapy.

PurposeDoxorubicin/cyclophosphamide followed by docetaxel chemotherapy (AC-D) is an intermediate risk factor (incidence of 10%–20%) for febrile neutropenia (FN) in breast cancer. However, the reported incidence of FN while using this regimen was obtained mostly from Western breast cancer patients, with little data available from Asian patients. This study aimed to assess the incidence of FN in Korean breast cancer patients and to describe clinical variables related to FN.MethodsFrom September 2010 to February 2013, data from the Yonsei Cancer Center registry of breast cancer patients who received neoadjuvant or adjuvant chemotherapy with four cycles of AC-D (60 mg/m2 doxorubicin, 600 mg/m2 cyclophosphamide every 3 weeks for four cycles followed by 75 mg/m2 or 100 mg/m2 docetaxel every 3 weeks for four cycles) were analyzed. The incidence of FN, FN associated complications, dose reduction/delays, and relative dose intensity (RDI) were investigated.ResultsAmong the 254 patients reported to the registry, the FN incidence after AC-D chemotherapy was 29.5% (75/254), consisting of 25.2% (64/254) events during AC and 4.7% (12/254) during docetaxel chemotherapy. Dose reductions, delays, and RDI less than 85.0% during AC were observed in 16.5% (42/254), 19.5% (47/254), and 11.0% (28/254) of patients, respectively. Patients with FN events frequently experienced dose reduction/delays, which eventually led to a decreased RDI.ConclusionThe incidence of FN during AC-D neoadjuvant or adjuvant chemotherapy was higher than expected in Korean breast cancer patients. Whether these patients should be classified as a high-risk group for FN warrants future prospective studies.

Annual Patient and Caregiver Burden of Oncology Clinic Visits for Granulocyte-Colony Stimulating Factor (G-CSF) Therapy in the United States (US)

Introduction: Cancer patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drug therapy often have suppressed white blood cell counts and are at risk for febrile neutropenia (FN). Treatment with G-CSFs at least 24 hours after administration of myelosuppressive chemotherapy is indicated for patients with a clinically significant incidence of FN. In the US most doses of G-CSFs are administered in the clinic during separate visits after the chemotherapy session, to ensure on label administration. Patients must return to the clinic, usually the next day, for G-CSF administration, often accompanied by a family member or other informal caregiver. Self-administration in the home is sometimes an option, but can be an unattractive option, due to high pharmacy co-pays, patient discomfort with self-treatment, physician concerns, etc. Therefore, the time and economic burden on patients and informal caregivers of clinic visits for G-CSF injections may be significant, and has not previously been estimated from a societal perspective in the US.Methods: The total national patient and informal caregiver time and cost burden of prophylactic G-CSF clinic (physician office and hospital outpatient) visits was projected for calendar year 2015. Total annual visits for G-CSF injections following myelosuppressive chemotherapy for non-myeloid malignancies were estimated from models using data collected from the oncology literature, cancer patient databases (SEER, Oncology Services Comprehensive Electronic Records (OSCER)), and publically-available G-CSF revenue and pricing data. Average patient and caregiver travel times per visit, plus time in the clinic, were estimated from responses to a questionnaire completed by 598 patients in an ongoing prospective observational study (Prospective Study of the Relationship between Chemotherapy Dose Intensity and Mortality in Early-Stage (I-III) Breast Cancer Patients (CABS)). Total travel time plus time in the clinic for the G-CSF injection were cumulated for both patients and informal caregivers accompanying patients to the clinic. Total travel distance in miles and travel costs were estimated. The opportunity cost of time spent by patients and caregivers in G-CSF visits was monetized using national hourly wage data from the Bureau of Labor Statistics.Results: The estimated total number of clinic visits for G-CSF injections in the United States following myelosuppressive chemotherapy for non-myeloid malignancies is 1.7 million visits for approximately 400,000 patients in 2015. Two-thirds of patients are expected to be accompanied to the visit by an informal caregiver (1.1 million visits). Mean(SD) travel time (round-trip) per visit is estimated at 62(50) minutes; with mean(SD) time in the clinic of 41(68) minutes. Mean(SD) travel distance round-trip is estimated to be 35(28) miles. The total national patient and informal caregiver time commitment for one year for travel to and from the clinic, plus time at the clinic, is estimated at 4.86 million hours (12.1 hours per patient), with their time valued at approximately $87.2 million ($218 per patient). The cumulative annual travel distance for G-CSF clinic visits is estimated at 59.7 million miles, at a total transportation cost of $28.2 million ($70 per patient). The total economic impact of time plus transportation costs is $115 million.Table 12015 Estimated Patient and Caregiver Burden of G-CSF Clinic VisitsClinic VisitsCumulative Time (hours)Cumulative Travel MilesCumulative Time+Travel CostsPatients1,700,0002,921,16759,726,667$72.4 millionCaregivers1,127,1001,936,73439,598,780$43.0 millionTotal1,700,0004,857,90159,726,667$115.4 millionConclusions: The patient and informal caregiver burden of clinic visits for G-CSF therapy following myelosuppressive chemotherapy is a significant addition to the total disease burden borne by patients and their families. Efforts to reduce this burden for the patient and caregiver should be pursued. DisclosuresStephens:Amgen, Inc.: Consultancy; InnoPeritus: Consultancy. Li:Amgen, Inc.: Employment, Equity Ownership. Reiner:Amgen, Inc.: Employment. Sheldon:Amgen, Inc.: Employment. Tzivelekis:Amgen Inc.: Employment, Equity Ownership.

Chemotherapy treatment patterns and neutropenia management in gastric cancer.

Potentially myelosuppressive doublet and triplet chemotherapy combination regimens are considered the most active treatments in gastric cancer. This multicenter prospective observational study was designed to gain insight into the chemotherapy regimens being used in Europe and to evaluate neutropenia management in patients identified as at high risk for febrile neutropenia (FN). Eligible patients had gastric cancer, were scheduled for ≥ 3 cycles of myelosuppressive chemotherapy, and had an investigator-assessed overall FN risk ≥ 20%. Data were collected for up to ten cycles. The primary endpoint was the proportion of patients who received granulocyte colony stimulating factor (G-CSF) primary prophylaxis (defined as G-CSF initiated on days 1-7 of cycle 1). Secondary endpoints included FN incidence, chemotherapy administration, and G-CSF use. Of 199 patients who met the eligibility criteria and started at least one cycle of chemotherapy, mean age was 63 years, 76% were men, 83% had an ECOG score of 0 or 1, 54% had metastatic disease, and 24% had received prior chemotherapy. A total of 27 different backbone regimens were given; the most common regimen was modified docetaxel, cisplatin, and 5-fluorouracil (DCF). Despite all patients having been identified as having a ≥ 20% FN risk, only 70 (35%) received G-CSF primary prophylaxis. FN occurred in 14 patients overall (7%). Most FN events occurred in patients who received DCF/modified DCF (9/14 events, 64%). The results of this study reveal a high use of myelotoxic treatment regimens in gastric cancer in Europe and low adherence to clinical practice guidelines for the use of primary and secondary G-CSF prophylaxis for FN.

Pegfilgrastim prophylaxis in patients at different levels of risk for chemotherapy-associated febrile neutropenia: an observational study

Background:Guidelines for using granulocyte colony-stimulating factor (G-CSF) in patients receiving chemotherapies with 10–20% (intermediate) risk for febrile neutropenia (FN) recommend additional assessment of patient-related FN risk factors.Objective:The current study evaluated adherence to guideline recommendations and analysed modalities of pegfilgrastim use.Methods:Adult cancer patients scheduled to receive a chemotherapy regimen assessed by the investigators as intermediate FN risk and who received pegfilgrastim were prospectively enrolled in this observational study from 2007–2010. Risk factors at study entry, treatment modalities and FN assessment were documented by investigators, whereas guideline adherence was centrally checked in a post-hoc analysis, according to guideline categorizations.Results:Thirty-seven centres enrolled 335 evaluable patients with solid and hematologic neoplasias. Although physicians initially rated the FN risk of all chemotherapies as intermediate, after central re-assessment this applied only to 63.9% of regimens; 21.2% were reassessed as low risk and 14.9% as high risk. Pegfilgrastim was used as primary prophylaxis in 80.3% of all patients. The most frequent FN risk factors considered by physicians when deciding to use pegfilgrastim were female gender, advanced disease, age ≥65 years, and anaemia. FN incidence was higher in patients with ≥4 FN risk factors than those with <4 risk factors (10% vs. 4.3%; p = 0.055) and in patients with severe comorbidity than those without (13.6% vs. 4.5%; p = 0.014). Overall FN rate was 5.7%.Limitations:Due to the observational design of the study, findings are descriptive in nature. Post-hoc assessment of chemotherapy FN risk was determined by author’s opinion in some cases.Conclusions:Overall, there was good adherence of Austrian physicians to guideline recommendations; however, there are chemotherapy regimens and clinical settings in which FN risk assignment is unclear in the literature. FN incidence with pegfilgrastim prophylaxis was similar to that reported in other observational and randomized studies.

Chemotherapy (CT) treatment patterns and neutropenia management in gastric cancer patients (pts) receiving myelosuppressive chemotherapy in Europe.

128 Background: Granulocyte-colony stimulating factor (G-CSF) primary prophylaxis (PP) is recommended for pts undergoing CT who are at overall high risk for febrile neutropenia (FN). No single CT regimen is recognized as standard in gastric cancer and few regimens are represented in G-CSF guidelines. We therefore evaluated neutropenia management in pts receiving CT for gastric cancer. Methods: This was a multicentre prospective observational study that enrolled pts sequentially from 11/2009 to 06/2011. Adult gastric cancer pts (any stage) with ≥3 cycles of myelosuppressive CT scheduled and an investigator-assessed overall FN risk ≥20% were eligible. The primary outcome was the proportion of pts who received PP G-CSF (G-CSF in days 1-7 of cycle 1). Secondary outcomes included FN incidence, chemotherapy administration, and G-CSF use. Posthoc analyses investigated the subgroup who received DCF, including modifications from standard DCF (Van Cutsem. JCO. 2006), and the G-CSF support given up to the first FN (G-CSF prophylaxis given per label in each cycle up to that in which FN occurred). Results: Of 209 pts enrolled, 199 were eligible and their data analyzed. The mean (±SD) age was 62 (±12) years, 76% were male, 17% were ECOG 2 and none ECOG 3-4; 47% were treatment naïve. Planned CT was palliative in 74% of pts; overall, 27 different backbone regimens were planned (10 triplet, 12 doublet, 5 single drug regimens). The most common regimen used was DCF (54 pts, 27%), predominantly given as modified DCF (41 pts). Despite being assessed as high risk for FN, G-CSF PP was administered to only 35% of pts overall (n=70; 54 pegfilgrastim, 16 daily G-CSF) and to 69% of pts who received DCF. FN occurred in 14 pts (10%), 9 of whom received DCF. A large majority of FN pts (12/14, 86%) had not received prophylactic G-CSF per label up to the first FN occurrence; furthermore, 86% of FN pts did not receive G-CSF prophylaxis in the cycle following the FN event. Conclusions: The variety of CT used, frequent modifications to standard CT, and presence of pt risk factors makes FN risk estimation difficult in gastric cancer. Improved risk assessment and appropriate targeting of G-CSF PP to high risk pts is needed.

Utility of routine nurse assessment of the risk of chemotherapy-induced febrile neutropenia

Evidence-based guidelines recommend that patients at high risk (> or = 20%) for febrile neutropenia (FN) should receive prophylactic colony-stimulating factors (Aapro et al., 2006; Kouroukis et al., 2008; National Comprehensive Cancer Network [NCCN], 2008; Smith et al., 2006). We studied the utility of having nurses routinely assess FN risk in new patients before the initiation of chemotherapy. Fifteen nurses used a standardized tool to evaluate FN risk in 150 patients. In 94% of patients studied, nurses detected risk factors that prompted interventions to reduce the incidence of FN. On final evaluation, 67% of nurses said the use of a standardized tool helped them to identify patients at risk for FN, and 73% planned to assess FN risk routinely. Thus, it is feasible and valuable for nurses to assess FN risk using a standardized checklist prior to the initiation of chemotherapy.

Risk Factors for Febrile Neutropenia among Breast, Lung, and Colorectal Cancer Patients: A Retrospective Analysis of Health Plan Databases

Chemotherapy regimens, patient factors, and the use of colony stimulating factor (CSF) influence cancer patients' risk for febrile neutropenia (FN) when they receive myelosuppressive chemotherapy. The incidence of FN and patient factors influencing that risk are relatively unknown in community settings. Using claims from Medicare, Medicaid and two private health insurance plan enrollees linked to the Puget Sound SEER registry, we examined the incidence of FN among breast, lung and colorectal cancer patients diagnosed 2002–05 who received adjuvant chemotherapy. We used logistic regression models to determine factors influencing the risk for FN within the first chemotherapy cycle, controlling for cancer stage, age, sex, race, comorbidities, chemotherapy-regimen related FN risk (as designated by the National Comprehensive Cancer Network), CSF use, health insurance type, and surgery or radiation ≤30 days from administration of first chemotherapy. Over the time horizon, 1096 breast, 1142 lung, and 755 colorectal cancer patients received chemotherapy. The incidence of any FN in the first chemotherapy cycle was (counts per 100 recipients by high, intermediate, and low-risk myelosuppressive chemotherapy according to NCCN categories respectively) 7.36, 10.0, 4.70 for breast cancer, 17.12, 14.15, 12.22 for lung cancer, and 25.0, 8.96, 6.37 for colorectal cancer. Significant predictors (p<0.05) of any FN were: breast cancer—radiation ≤ 30 days from first chemotherapy administration (OR 2.90, 95% CI 1.21–6.94), other non-black race vs. white race (OR 2.82, 95% CI 1.29–6.17), or Medicaid insurance (OR 2.31, 95% CI 1.10–4.89); lung cancer—radiation ≤ 30 days from first chemotherapy administration (OR 1.63, 95% CI 1.01–2.61), surgery ≤ 30 days from first chemotherapy administration (OR 2.08, 95% CI 1.02–4.25), Medicaid insurance (OR 2.29, 95% CI 1.08–4.84), or a Charlson comorbidity score ≥ 2 (OR 2.56, 95% CI 1.11–5.91); colorectal cancer—female gender (OR 1.86, 95% CI 1.02–3.41) or high myelosuppressive risk chemotherapy regimen (OR 7.66, 95% CI 2.95–19.89). In this analysis, predictors of FN varied between cancers. Limitations of this analysis include lack of information about chemotherapy and CSF doses, as this is not captured in the SEER registry or claims data. These results indicate that several factors may interact to influence a patient's likelihood of developing FN in the first cycle of adjuvant chemotherapy.

ELYPSE 2: A prospective randomized trial comparing filgrastim (G-CSF) in primary and secondary prophylaxis in patients (pts) at high risk for febrile neutropenia (FN)

8614 Background: FN is a frequent life-threatening consequence of cytotoxic chemotherapy (CT). G-CSF reduces the risk of FN, but primary (1ry) prophylaxis using G-CSF may be cost efficient only if FN incidence is ≥20%. The identification of pts at high risk for FN with simple criterias would be useful in clinical practice. Here we report a randomized phase II trial comparing G-CSF in 1ry vs 2ry prophylaxis in a high risk group of pts (based on our risk model JCO 1996;14:737, Br J Cancer 2003;88:181). Methods: Pts ≥18 years with solid tumors or NHL at high risk for FN after CT were incluable: these were pts with day 1 or day 5 lymphocytes (Ly) count ≤700/μL AND “high risk CT” (HRCT) In pts with d1 and d5 Ly ≤700/μL, the observed incidence of FN was 40% and 66% respectively G-CSF (300 to 480μg/d from d6–12) was randomized either as in 1ry prophylaxis (Arm 1), or as 2ry prophylaxis after FN (Arm 2). Primary endpoint was the rate of grade 4 FN. Hypothesis was a reduction of 40% of the risk of FN with 1ry prophylaxis. Results: Between 03/97 and 12/04, 137 pts were included in 7 centers. The median age was 53 years (range 18–80) with 54% males. Most frequent tumors were sarcomas (36%), breast carcinomas (18%), lymphomas (15%), head and neck carcinomas (10%), and lung carcinomas (6%). 23% patients had PS&gt;1 at the first line of chemotherapy. No difference was observed in terms of duration of hospitalization or antibiotherapy. Median number of days of G-CSF administration was 14 days (0–24) vs 0 (0–17) days (p&lt;0.0000). After the 1st course, grade 4 FN was 38% in Arm 2 (2ry prophylaxis) and 25% in Arm 1 (1ry prophylaxis), showing a 34% reduction of FN in arm 1 (p=0.14): 1ry prophylaxis was associated with a significant reduction of FN using logistic regression (p=0.04). Incidence of FN after the 2 course in pts receiving 2ry prophylaxis was 22%. Among the subgroup of pts with PS&gt;2 and Ly ≤700/μL, (a group with a reported 20% risk for early death, Br J Cancer 2001;85:816), 2 of 8 patients (25%) died after the 1st course, vs 0/13 in the G-CSF group (p=0.05). This difference was not significant in the whole group. Conclusions: This study confirms that lymphopenic pts receiving HRCT are a high risk group of pts for FN for whom 1ry prophylaxis with G-CSF reduces the incidence of FN. [Table: see text]