Administration Of Pegfilgrastim Research Articles

The Safety and Efficacy Administration of Pegfilgrastim on Days +1, +5, +7 versus Filgrastim Day 7 in Patients Post Autologous Stem Cell Transplant in a Developing Country

The Safety and Efficacy Administration of Pegfilgrastim on Days +1, +5, +7 versus Filgrastim Day 7 in Patients Post Autologous Stem Cell Transplant in a Developing Country

Pegfilgrastim-induced fatigue and leukocytosis improved following dose reduction in a young patient with breast cancer: A case report.

Dose-dense (DD) chemotherapy is a treatment option for patients with high-risk premenopausal breast cancer. Pegfilgrastim may be administered as prophylaxis against the development of febrile neutropenia and enables the continuation of the DD schedule; however, it is associated with adverse effects, including bone and muscle pain and fatigue. We herein describe our experience with pegfilgrastim administration alongside DD chemotherapy in a patient with breast cancer. A 29-year-old female patient was diagnosed with locally advanced breast cancer during lactation. The patient was diagnosed with cT2N1M0, stage IIB triple-negative breast cancer and underwent four cycles of DD chemotherapy with epirubicin plus cyclophosphamide, followed by four cycles of docetaxel (DTX) every 2 weeks preoperatively, with 3.6 mg pegfilgrastim administered subcutaneously on day 3 of each cycle. The absolute neutrophil count (ANC) was 2,700, 8,400, 11,100, 13,300 and 15,000/mm3 on day 1 of each cycle. The patient experienced fatigue after each pegfilgrastim injection and was considered to be a high responder to pegfilgrastim. Therefore, 1.8 mg pegfilgrastim on day 3 of the first DD-DTX cycle was recommended. On day 1 of the second cycle, the ANC was 13,090/mm3. The patient experienced less fatigue after the administration of 1.8 mg pegfilgrastim, but there was a significant decline in her performance status. As there is currently no evidence of pegfilgrastim dose reduction to below 1.8 mg, pegfilgrastim was omitted on day 3. On day 14, the patient developed viral enteritis, fever (38°C), and an ANC of 297/mm3. Therefore, the third cycle was postponed. After 1 week, the patient's ANC recovered to 2,480/mm3 and she was administered the third cycle with 3.6 mg pegfilgrastim on day 3. Between January 2015 and March 2018, a total of 55 patients with breast cancer received chemotherapy with pegfilgrastim at the Shiga General Hospital. No patients other than the one presented herein experienced leukocytosis during chemotherapy. Although this was a rare complication, a dose of 1.8 mg pegfilgrastim was effective in palliating the patient's symptoms and preventing DD chemotherapy discontinuation.

Retrospective Analysis of Clinical Outcomes Associated With the Use of Pegfilgrastim On-body Injector in Patients Receiving Chemotherapy Requiring Granulocyte Colony-Stimulating Factor Support.

Objectives: Pegfilgrastim is a granulocyte colony-stimulating factor (G-CSF) used as primary prophylaxis in patients receiving myelosuppressive chemotherapy regimens that have greater than 20% risk of developing febrile neutropenia (FN). Historically, pegfilgrastim has been administered 24 to 72 hours after chemotherapy, necessitating a return to clinic to receive the provider-administered injection. An alternative option is the pegfilgrastim on-body injector (OBI). With the OBI device, patients have their pegfilgrastim administered 27 hours after receiving chemotherapy while remaining at home, avoiding an additional clinic appointment. Concerns with pegfilgrastim OBI include lack of experience with the device in both the patient and provider, device-related failures, and the success of delivery. This study evaluates pegfilgrastim OBI failure rates through associated patient outcomes among cancer patients receiving chemotherapy requiring G-CSF. Methods: A retrospective electronic chart review was conducted of adult patients with cancer who received chemotherapy and pegfilgrastim OBI from July 1, 2016, to July 31, 2018. The primary objective of this study was the incidence of FN in patients receiving pegfilgrastim OBI. Results: There were no reported cases of hospitalization due to FN in patients who received pegfilgrastim OBI. Dose delays and dosage modifications were not observed in our review. The OBI device failure rate was found to be low (1.92%). Conclusion: The low device failure rate from this study suggests that the OBI is a viable option for administration of pegfilgrastim in patients receiving chemotherapy requiring G-CSF.

P-044 - Efficacy and safety of early administration of pegfilgrastim in patients with esophageal cancer treated by docetaxel, cisplatin, and 5-fluorouracil (DCF): a phase 2 prospective study

P-044 - Efficacy and safety of early administration of pegfilgrastim in patients with esophageal cancer treated by docetaxel, cisplatin, and 5-fluorouracil (DCF): a phase 2 prospective study

Trends in Neutropenia-Related Hospitalization in Older Patients with Non-Hodgkin Lymphoma (NHL) Receiving Myelosuppressive Chemotherapy in the United States: 1995-2015

Introduction: Febrile neutropenia (FN) is a serious complication among patients receiving myelosuppressive chemotherapy (MC). Clinical trials have shown efficacy of primary prophylaxis with granulocyte colony-stimulating factor (PP-GCSF) in reducing FN risk, but few population-based studies have examined trends in PP-GCSF use and FN incidence in older patients over the past 20 years. We describe trends in MC regimens by FN risk category, PP-GCSF use, and risk of neutropenia (NP)-related hospitalization focusing on older NHL patients initiating MC.Methods: We identified patients (age ≥ 66 years) diagnosed with NHL and initiating MC each year 1995-2015 using Medicare 5% (1994-2007) and 20% (2007-2015) sample data. We required patients to be continuously enrolled in Medicare Part A and B for 12 months before MC initiation (first MC treatment in the year with no claims for MC agents in the preceding 12 months) and to survive ≥ 6 days after initiation. The first MC cycle started on the MC initiation date (day 1) and ended at the next administration at least 6 days, but no more than 35 days, after initiation. If no second cycle started before day 35, the first cycle was considered completed at the earliest of day 35 after initiation, the day before regimen change, death, disenrollment from Part A or B, or September 30, 2015.Chemotherapy regimen was defined based on MC agents on Part A outpatient (OP) or Part B (PB) claims from day 1-day 6 of the first cycle and, on the same claims, an ICD-9-CM diagnosis code for NHL. Based on the National Comprehensive Cancer Network guidelines, regimens with FN risk >20% and 10%-20% were classified as high and intermediate FN risk categories, respectively. Patients receiving MC agents but not high or intermediate FN risk regimens were classified as “Other” FN risk category. PP-GCSF use was defined as an administration of pegfilgrastim or any short-acting CSF (filgrastim, tbo-filgrastim, filgrastim-sndz, or sargramostim) in OP/PB claims up to 5 days after first cycle chemotherapy completion. NP-related hospitalization was identified from Part A inpatient claims with ICD-9-CM diagnosis code 288.0X in the first five positions between day 7 and the last day of the cycle. We describe trends in proportions of patients receiving MC regimens by FN risk category, with PP-GCSF use, and with NP-related hospitalization in the first cycle. Trends in NP-related hospitalization rates were further evaluated using a logistic regression model with calendar year treated as a continuous variable and functional form estimated by a penalized spline after adjusting for age, race, baseline hospital length of stay, baseline NP-related hospitalization, number of comorbid conditions, and MC FN risk category.Results: Yearly cohorts included 538-717 eligible patients, 1995-2007, and 1877-2640, 2008-2015. Proportions of patients aged ≥80 years increased from 39% in 1995 to 44% in 2015. Proportions receiving high/intermediate FN risk regimens were <20% before 1997, 36% in 1997, and 40%-46% 1998-2015 (Figure 1). Most patients receiving high/intermediate risk regimens (88%-96%) received CHOP-21 (cyclophosphamide, doxorubicin, and vincristine every 21 days with or without rituximab).Overall, PP-GCSF use increased from 8% in 1995 to 60% in 2015, mainly due to introduction of pegfilgrastim in 2002 (Figure 2). PP-GCSF use was more common in patients receiving high/intermediate FN risk regimens than in patients receiving other regimens (Figure 3). Overall, unadjusted incidence of NP-related hospitalization decreased from 7% in 1995 to 4% in 2015 (Figure 4). Change point in trend was detected at 2010; incidence of NP-related hospitalization decreased, on average, 6% each year before 2010 (p<0.0001) and was flat from 2010 (p=0.6) after adjustment for changed patient characteristics.Conclusions: Among older patients diagnosed with NHL receiving MC, 1995-2015, PP-GCSF use increased substantially after 2002. Over the same 20-year period, incidence of NP-related hospitalization in the first cycle decreased, on average, 6% each year before 2010 and was flat from 2010. Further studies are needed to understand overall decreasing trends in NP-related hospitalization and effects of changes in chemotherapy and FN management. [Display omitted] DisclosuresLiu:FibroGen Inc.: Consultancy. Gawade:Amgen: Employment, Equity Ownership. Kim:Amgen: Employment, Equity Ownership. Bensink:Amgen: Employment, Equity Ownership. Chandler:Amgen: Employment, Equity Ownership.

Phase II Study of Stimulation of Healthy Sibling Donors with Single-Shot Pegfilgrastim - Update (EUDRACT Nr: 2005-004971-39)

Introduction: For allogeneic stem cell donation it is current practice to mobilize with G-CSF bid for 5 days. Here, the feasibility of mobilizing with a single injection of pegfiligrastim was examined in a phase II study with an emphasis on donor safety and product composition.Results: 28 sibling donors (14 female, 14 male) of median age 50 (range 22 - 69) years were included in the study. The median donor weight was 80 (range 45 - 119) kg and that of recipients was 75 (range 47 - 127) kg. Large volume apheresis (4 x total blood volume) was possible in 26 donors 4 days after the administration of pegfilgrastim 12 mg s.c. The aphereses were performed when CD34+cells exceeded 10/µl peripheral blood, median CD34+concentration prior to apheresis being 66.25 (range 22.8 - 136.6) cells/µl. White blood cell (WBC) concentration peaked on day 4 of stimulation with a median 52.55 (range 22.8 - 85) GPT/l. The lactate dehydrogenase (LDH) and C-reactive protein (CRP) levels increased to a median 2.55 (range 1.36 - 6.02) and 3.23 (range 0.47 - 15.13) x upper limit of normal (ULN) respectively. There were no changes in creatinine, electrolytes or transaminases. Two donors required filgrastim in addition to the pegylated G-CSF, with the aphereses being performed on day 5 after pegfilgrastim. Six donors required more than one apheresis.In 25/28 donors, a median of 6.5 (range 4.6 - 14.5) x106CD34+/kg recipient body weight were collected. In three donors the yield was below 4x106CD34+/kg recipient body weight, i.e. 3, 3.4 and 3.6 respectively. The yield of CD34+/CD133+cells was median 4.45 (range 2.74 - 12.5) x106/kg recipient body weight.In 27/28 cell concentrates, the number of CFU-GM amounted to median 126 (range 65 - 323) /105mononuclear cells. The yield of CD3+cells was median 3.25 (range 1.4 - 6.2) x108/kg recipient body weight. The CD3+/CD8+and CD3+/CD4+ratios were 0.92 (range 0.33 - 2.58) and 2.14 (range 0.85 - 4.16) x108/kg, respectively. The yield of natural killer (NK) cells was median 0.4 (range 0.2 - 1) x108/kg recipient body weight.On the first collection day, 27/28 donors reported through a standardized questionnaire that the stimulation was well tolerated, although 26 experienced bone pain, which was strong in 11 cases. Other side effects such as cephalea, tiredness or inability to work were reported only in single cases.Hematopoietic Stem Cell Transplants were performed without complications. WBC recovery occurred on median day 14 (range 8 - 34) after HSCT. Acute GvHD > Gr. 3 was noted in one patient only. No rejection was observed.Conclusion: Pegfilgrastim is a feasible alternative to conventional bid filgrastim for stem cell mobilization. A single application was able to mobilize sufficient CD34+/CD133+cells into the peripheral blood for successful collections. The most frequent adverse effects were elevation of CRP and/or LDH and bone pain. DisclosuresNiederwieser:Miltenyi: Speakers Bureau; Novartis: Research Funding.

Efficacy of pegfilgrastim administration in patients with esophageal cancer treated with docetaxel, cisplatin, and 5-fluorouracil.

Chemotherapy is among the standard treatments for esophageal cancer. The docetaxel, 5-fluorouracil, and cisplatin (DCF) protocol yields a better response rate than 5-fluorouracil plus cisplatin. However, the incidence of side effects, such as febrile neutropenia and hematologic toxicity, is also significantly high with the DCF protocol. The granulocyte colony-stimulating factor and pegfilgrastim are prophylactically administered to prevent febrile neutropenia. This retrospective study evaluated the efficacy and safety of pegfilgrastim in patients receiving DCF therapy. Of the 65 patients who were administered DCF therapy in our hospital from 2011 through 2016, 21 received pegfilgrastim 24 hours or more after the end of chemotherapy. The protocol comprised 70 mg/m2 each of docetaxel and cisplatin on day 1 and 700 mg/m2 5-fluorouracil on days 1 to 5 via intravenous injection in a 3-week cycle. The primary endpoint was the rate of grade 3-4 neutropenia and febrile neutropenia. The mean patient age was 66.4 years. The incidence of grade 3 and 4 neutropenia was 14.2 % and 11.4 %, respectively, in the pegfilgrastim group and 31.9 % and 37.8 %, respectively, in the non-pegfilgrastim group. The incidence of febrile neutropenia in the pegfilgrastim group and non-pegfilgrastim group was 11.4 % and 40.3 %, respectively. Statistical analysis showed that the incidence of neutropenia and febrile neutropenia was significantly different (p<0.05) between the two groups. Pegfilgrastim prevents severe neutropenia and febrile neutropenia in patients with esophageal cancer who are treated according to the DCF protocol.

PS02.099: EFFORTS IN PROPHYLAXIS OF FEBRILE NEUTROPENIA IN DCF THERAPY FOR ESOPHAGEAL CANCER

Abstract Background DCF therapy (5-FU + CDDP + Docetaxel) for esophageal cancer is known to have strong anti-tumor effect but the incidence of bone marrow suppression (BMS) and febrile neutropenia (FN) after DCF therapy has been frequent and patients is often forced to reduce the dose of anti-cancer drug or discontinue of chemotherapy. We clarified the influence of prophylactic administration of a long-acting G-CSF, pegfilgrastim, in DCF therapy for esophageal cancer on the incidence of adverse events and anti-tumor effect. Methods From March, 2011 to July, 2017, 87 patients underwent DCF therapy (Docetaxel 60mg/m2 D1, CDDP 60mg/m2 D1, 5-FU 800mg/m2 D1–5) for esophageal squamous cell carcinoma above cStage II (33 patients administered pegfilgrastim, P group; 54 patients without pegfilgrastim, N group). We investigated the influence of pegfilgrastim on the incidence of adverse events in both groups according to CTCAE v4.0 grading system. And we investigated anti-tumor effects assessed by image examination in all patients and 47 surgically resected specimens. Results The incidence of leukocytopenia and neutropenia in P group were significantly lower than that in N group (15.2% vs 57.4%, P &lt; 0.001; 21.2% vs 64.8%, P &lt; 0.001, respectively). The incidence of FN in P group tended to be lower than that in N group (9.1% vs 20.4%, P = 0.233). Significantly more patients in N group suffered dose reduction or discontinuation of chemotherapy due to BMS or FN (30.3% vs 72.2%, P &lt; 0.001). Relative dose intensity of 5-FU in P group was significantly higher than that in N group (95.6% vs 82.5%, P = &lt; 0.001). In endoscopically evaluated response after 2 courses of DCF therapy, the reductive effects in the patients in P group significantly better than in those in N group (PR &lt; ; 78.1% vs 44.0%, P = 0.002). The overall response rate was also significantly better in the patients in P group than in those in N group (PR &lt; ; 60.6% vs 35.2%, P = 0.021). Histopathological responses in surgically resected tumor in P group tended to be better than N group (Grade 1b &lt; ; 47.1% vs 33.3%, P = 0.352). Conclusion DCF chemotherapy with prophylactic administration of pegfilgrastim may be an option for safe and effective chemotherapy for advanced esophageal cancer. Disclosure All authors have declared no conflicts of interest.

Overuse and underuse of pegfilgrastim for primary prophylaxis of febrile neutropenia.

Guidelines recommend pegfilgrastim for primary prophylaxis of febrile neutropenia after highly myelosuppressive chemotherapy. While deviations from guidelines could result in overuse and increased costs, underuse is also a concern and could compromise quality of care. Our objectives were to evaluate guideline adherence and quantify the extent to which physician heterogeneity may influence pegfilgrastim use. We randomly sampled 550 patients from a retrospective cohort of those who received infusions at an academic cancer center between 1 September 2013 and 1 September 2014. Electronic medical and drug dispensing records provided information on patient characteristics, chemotherapy characteristics, prescribing physician, and pegfilgrastim administration. We included 154 patients treated by 25 physicians. About half of patients were male and mean age was 61.3 years. Forty (26.1%) patients had no febrile neutropenia risk factors, 62 (40.5%) had one, and 51 (33.3%) had two or more. Thirty patients (19.5%) received pegfilgrastim, of which 12 (40%) received palliative chemotherapy. Nine (60%) of 15 patients on a regimen with a febrile neutropenia risk ≥ 20% received pegfilgrastim. Pegfilgrastim use significantly varied by cancer type (p < 0.01), chemotherapy regimen (p < 0.001), and regimen febrile neutropenia risk (p < 0.001). Multivariable analysis reaffirmed the association between chemotherapy regimen febrile neutropenia risk ≥ 20% and pegfilgrastim use (odds ratio (OR) = 10.1, 95% confidence interval (CI): 1.6-62.7) and suggested that 31% (95% CI: 8%-71%) of the variation in use was attributable to physician characteristics. Pegfilgrastim was potentially overused for palliative chemotherapy and underused for chemotherapy regimens with febrile neutropenia risk ≥ 20%. Successful interventions to modify prescribing practices likely require an understanding of the relationship between specific physician characteristics and pegfilgrastim use.

A single-arm, retrospective analysis of the incidence of febrile neutropenia using same-day versus next-day pegfilgrastim in patients with gastrointestinal cancers treated with FOLFOX or FOLFIRI.

Practice patterns of same-day versus next-day pegfilgrastim vary in numerous practice settings across the country. Current utilization with same-day pegfilgrastim reduced overall visits and reduced treatment time for chemotherapy administration. To assess the efficacy and safety of same-day versus next-day pegfilgrastim in patients with colorectal cancer. Patient data was extracted through electronic health records (EHR) search of ICD-9 codes that matched patients with CRC and treated with FOLFOX or FOLFIRI from November 2013 to January 2016. The incidence rates of primary and secondary endpoints were estimated for patients who received either FOLFOX or FOLFIRI and same-day pegfilgrastim with 2-sided 95% confidence intervals. Fisher's exact test for 2 × 2 contingency tables was used to compare the incidence of primary and secondary endpoints between the two study groups performed at the α = 0.05 significance level. A study by Hecht et al. served as a historical control for next-day pegfilgrastim. A total of 109 out of an initial 330 patients with appropriate ICD-9 criteria were eligible for study inclusion. The primary endpoint of incidence of FN recorded over 4 chemotherapy cycles with either FOLFOX6 or FOLFIRI occurred in 3.7% of patients (95% CI, 1.1-9.4%). Secondary endpoints also occurred with a relatively low incidence: 13 patients developed grades 3/4 neutropenia (11.9%; 95% CI, 7.0-19.5%); 11 patients required dose reductions because of neutropenia or FN (10.1%; 95% CI, 5.6-17.3%); and 5 patients were hospitalized due to neutropenia or FN (4.6%; 1.7-10.6%). There were 4 reported events of FN (3.2%; 95% CI, 1.0-8.3%) for those who received next-day pegfilgrastim compared to 11 events in the placebo group (9.4%; 95% CI, 5.1-16.4%). The incidence of dose delays or dose reductions due to neutropenia or FN were 5 (4.1%, 95% CI, 1.5-9.4%) in the next-day pegfilgrastim group versus 26 (22.1%, 95% CI, 15.5-30.4%) in the placebo group. The study was retrospective in design and utilized a historical control for the comparator. Our study results suggest that same-day pegfilgrastim administration may be a safe and effective alternative to 24-h post-chemotherapy administration in patients with esophageal, gastric, appendiceal, or colorectal cancer undergoing treatment with FOLFOX or FOLFIRI.

A Randomized, Single-Blind Study Evaluating the Effect of a Bone Pain Education Video on Reported Bone Pain in Patients with Breast Cancer Receiving Chemotherapy and Pegfilgrastim

Background: Mild-to-moderate bone pain is the most commonly reported adverse event associated with pegfilgrastim. Aims: To investigate the effect of bone pain education on pegfilgrastim-related bone pain in patients with breast cancer receiving chemotherapy and pegfilgrastim. Design: Randomized, single-blind study. Settings: Forty-eight community oncology clinics throughout the United States. Participants: Three hundred women ≥18 years of age with newly diagnosed stage I -III breast cancer, who were planning ≥4 cycles of neoadjuvant or adjuvant chemotherapy with pegfilgrastim support starting in cycle 1. Methods: Patients were randomized 1:1 to view a general education DVD on chemotherapy side effects (GE-DVD) or a DVD on bone pain following chemotherapy and pegfilgrastim (BP-DVD). Patients recorded severity of bone pain on a scale of 0-10, location of pain, and use of bone pain medications (i.e., analgesics, antihistamines, and nonsteroidal anti-inflammatory drugs) for 5 days, beginning on the day of pegfilgrastim administration, in each of the first four chemotherapy cycles. Results: Patient-reported maximum bone pain was similar in the two groups (GE-DVD vs BP-DVD: cycle 1, 3.2 vs. 3.5, p = .3479; across all cycles, 4.1 vs. 4.6, p = .2196). Other measures of bone pain were also similar between the groups. Bone pain was highest in cycle 1 but decreased and then remained stable in subsequent cycles. Bone pain medication use was similar in both groups and was highest in cycle 1. Conclusions: The bone pain-specific education evaluated here did not improve perceptions of bone pain reported in this patient population.

Optimal timing for pegfilgrastim administration in Japanese breast cancer patients receiving intermediate-risk chemotherapies.

Background Pegfilgrastim is widely used for prophylaxis of febrile neutropenia (FN) in cancer patients receiving chemotherapies. However, the optimal timing of pegfilgrastim administration has not been established. Objective We investigated the effect of the timing of pegfilgrastim administration on the prevention of FN in patients with breast cancer undergoing intermediate-risk chemotherapies. Method We retrospectively analysed the incidence of FN in patients with breast cancer treated at our institution with intermediate-risk chemotherapies and primary or secondary prophylactic pegfilgrastim between 2015 and 2017. The impact of the timing of pegfilgrastim administration on the incidence of FN was evaluated by univariate and multivariate logistic regression analyses. Results Overall, 87 patients received a total of 318 chemotherapy cycles with pegfilgrastim, and 14 patients (16%) experienced FN. In univariate analyses, day 2 pegfilgrastim administration, age of > 65years, baseline haemoglobin < 12g/dL, prior history of FN, and presence of recurrent/metastatic disease trended toward an association with FN. Adjustment for these confounding risk factors revealed that day 2 pegfilgrastim administration was associated with a significantly increased risk of FN (odds ratio 11.0, p = 0.009). Conclusion Administrating pegfilgrastim on day 3 or later may prevent FN more effectively among Japanese breast cancer patients receiving intermediate-risk chemotherapies.

Outcomes of pegfilgrastim (PFG) administration on the same day vs the day after chemotherapy (CTX) in the prophylaxis of chemotherapy-induced (Febrile) neutropenia (CIN/FN): Systematic review and meta-analysis.

e14510Background: PFG should be administered 24-72 h after CTX, but there is a trend to administer it on the same day as CTX. The aim of our systematic review and meta-analysis (MA) was to compare ...

PHS123 - A Time-Motion Observational Study of Clinic Staff: Administration of Pegfilgrastim Primary Prophylaxis Via Next-Day Manual Injection and On-Body Injector (OBI)

Febrile neutropenia (FN) is a serious side effect of strong chemotherapy. Pegfilgrastim prophylaxis reduces the incidence of FN and should be administered at least 24 hours after myelosuppressive chemotherapy. Pegfilgrastim can be administered by manual injection using a prefilled syringe (PFS) or a more recently available on-body injector (OBI) applied at the end of chemotherapy with automatic administration of pegfilgrastim approximately 27 hours later. The study objective was to explore the practical implementation of PFS and OBI in the clinic setting. Trained data collectors observed clinic processes and staff time associated with pegfilgrastim administration via PFS and OBI application. Data from two sites provided information from 28 nurses on administration of pegfilgrastim via PFS to 53 patients (19 first-time patients) and application of the OBI to 75 patients (16 first-time patients). Mean (95% CI) clinic staff time was 5.7 minutes (4.2–7.2) for PFS administration and 7.3 minutes (6.3–8.4) for OBI application. The mean (95% CI) time for OBI first-time application, 13.8 minutes (10.1–17.4), was reduced to 5.6 minutes (5.3–5.9) for subsequent applications. After arriving at the clinic, the mean (95% CI) patient wait time for next-day PFS administration was 35.3 minutes (15.9–54.7). From a patient’s perspective, PFS administration required a return clinic visit the day after chemotherapy, resulting in significant wait time at the clinic- time not required for patients receiving pegfilgrastim via OBI. From a clinic’s perspective, individual patient visits needed to be accommodated for PFS administration- visits not required for patients receiving pegfilgrastim via OBI. OBI application time was significantly less for subsequent versus first-time patients, likely due to a reduced need for education on the device. Use of the OBI for pegfilgrastim prophylaxis may reduce the overall time burden for both patients and clinics.

The incidence and timing of leukocyte overshoot after pegfilgrastim administration.

Pegfilgrastim is a PEGylated formulation of filgrastim with a long half-life. It is highly convenient and less burdensome for patients. However, white blood cell count may temporarily increase after administration; in particular, a leukocyte overshoot may be observed. The present study retrospectively examined the incidence and timing of leukocyte overshoot after pegfilgrastim administration. Fifty-five patients (118 occasions of pegfilgrastim) were evaluated. Leukocyte overshoot was defined as white blood cell count ≥10,000/mm3 exceeding the reference value. Leukocyte overshoot was observed in 71.2% (84/118) occasions, in 76.4% (42/55) patients. The maximum white blood cell count ≥30,000/mm3 was observed in 30.5% (36/118) occasions in 45.5% (25/55) patients and was observed in 39.3% (33/84) occasions on day 1 after pegfilgrastim administration and 26.2% (22/84) on day 2. Leukocyte overshoot has been observed in only 23.1% (9/39) patients administered with normal granulocyte colony-stimulating factor. However, there were no patients with white blood cell counts ≥30,000/mm3. There was a higher frequency of occurrence of leukocyte overshoot in response to pegfilgrastim than in response to normal granulocyte colony-stimulating factor. High incidence of leukocyte overshoot was observed when blood was collected 1-2 days after administration of pegfilgrastim. It is important for patients to understand the characteristics of pegfilgrastim by conducting pharmaceutical guidance.

Granulocyte colony-stimulating factors used in clinical practice: PoloNord Registry-Based Cohort Italian Study.

Granulocyte colony-stimulating factors are widely used to reduce myelotoxicity of chemotherapy and to allow its regular administration. National and international guidelines regulate their use. The aim of the study was to evaluate the use of pegfilgrastim and filgrastim/lenograstim in clinical practice, adherence to ASCO and ESMO guidelines, chemotherapy-related complications and adverse reactions. Data from 645 consecutive patients and 3,150 chemotherapy administrations, receiving granulocyte colony-stimulating factors, as primary/secondary prophylaxis or therapeutic use, for the first time during a line of chemotherapy, were recorded from 08/2008 to 08/2011, in 10 Lombardy Italian cancer centers. Patients and chemotherapy administrations data were examined in a multiple logistic regression analysis model. Adherence to guidelines: primary prophylaxis, pegfilgrastim and filgrastim/ lenograstim 66%/47% (P = 0.002); secondary prophylaxis, 19.0%/26.8%; but 56.8%/ 53.6% including patients at high risk of febrile neutropenia with grade 3-4 neutropenia. Correct timing start (administration 24-72 h after chemotherapy): pegfilgrastim and filgrastim/lenograstim, 93.2%/61.5% (P <0.0001). Results suggest the more correct administration of pegfilgrastim as primary prophylaxis and timing start, compared to filgrastim/lenograstim. In secondary prophylaxis, the use of granulocyte colony-stimulating factors is extended beyond guideline recommendations to support patients at high risk of febrile neutropenia and to guarantee dose intensity. These outcomes suggest both the need of educational activities and the development of predictive tools to better define high risk patients and the use of granulocyte colony-stimulating factors.

Pharmacokinetic-pharmacodynamic modelling of neutrophil response to G-CSF in healthy subjects and patients with chemotherapy-induced neutropenia.

The objective of the present study was to use pharmacokinetic-pharmacodynamic modelling to characterize the effects of chemotherapy on the granulopoietic system and to predict the absolute neutrophil counts (ANCs) for patients with chemotherapy-induced neutropenia treated with filgrastim and pegfilgrastim. Data were extracted from 10 phase I-III studies conducted in 110 healthy adults, and 618 adult and 52 paediatric patients on chemotherapy following administration of filgrastim or pegfilgrastim. The structural model accounted for ANC dynamics and the effects of filgrastim and pegfilgrastim, chemotherapy and corticosteroids. The impact of neutrophils on drug disposition was based on a drug receptor-binding model that assumed quasi-equilibrium and stimulation of the production and maturation of neutrophils upon treatment. The chemotherapy and corticosteroid effects were represented by kinetic-pharmacodynamic-type models, where chemotherapy stimulated elimination of neutrophil precursors at the mitotic stage, and corticosteroids stimulated neutrophil production. The systemic half-lives of filgrastim (2.6h) and pegfilgrastim (10.1h) were as expected. The effective half-life of chemotherapy was 9.6h, with a 2-day killing effect. The rate of receptor elimination from mitotic compartments exhibited extreme interindividual variability (% coefficient of variation >200), suggesting marked differences in sensitivity to chemotherapy effects on ANCs. The stimulatory effects of pegfilgrastim were significantly greater than those of filgrastim. Model qualification confirmed the predictive capability of this model. This qualified model simulates the time course of ANC in the absence or presence of chemotherapy and predicts nadir, time to nadir and time of recovery from different grades of neutropenia upon treatment with filgrastim and pegfilgrastim.

Is it reasonable to administer pegfilgrastim on day 1 of a myelosuppressive chemotherapy regimen? A cost-utility analysis

BackgroundThere is recent evidence supporting the safety and efficacy of same-day dosing of pegfilgrastim in patients undergoing chemotherapy. ObjectiveTo determine the cost-effectiveness of pegfilgrastim on day 1 (D1) versus day 2 (D2) for primary prevention of neutropenia in women receiving chemotherapy. Materials and MethodsA cost-utility model was designed comparing standard D2 versus D1 administration of pegfilgrastim to ovarian cancer patients receiving chemotherapy with an intermediate risk (10–15%) of febrile neutropenia (FN). Rates of FN despite prophylaxis were modeled as 10% for D1 and 5% for D2. Societal costs associated with D2 injection ($175.71) were incorporated. Quality of life (QOL) was modeled from published data; we assumed a small decrement in QOL on treatment days. Sensitivity analyses were performed. ResultsD1 administration was less costly ($17,195 versus $17,681) and resulted in higher QOL (0.2298 quality adjusted life years (QALYs) versus 0.2288 QALYs) than D2. Results were sensitive to the risk of FN. D1 remained dominant or cost-effective (ICER less than $50,000/QALY) compared to D2 if the FN rate with D1 was assumed less than 14.5% (baseline estimate 10%). If the FN rate with D1 was assumed greater than or equal to 15%, D1 was not cost-effective compared to D2, with an ICER greater than $100,000/QALY. Findings are insensitive to variations in the modeled cost of treating FN, the additional cost of D2 injection, and the reduced QOL associated with treatment visits. ConclusionAdministration of D1 pegfilgrastim is cost-effective in women with ovarian cancer who are treated with intermediate risk chemotherapy.

Administration options for pegfilgrastim prophylaxis: patient and physician preferences from a cross-sectional survey.

Although clinical guidelines recommend administration of pegfilgrastim 1-4days after a myelosuppressive chemotherapy cycle to decrease the incidence of febrile neutropenia (FN), some physicians administer pegfilgrastim on the same day as chemotherapy administration. A novel on-body injector (OBI) that automatically delivers pegfilgrastim the day after chemotherapy is also available. Our objective was to estimate patient and physician preferences among the pegfilgrastim administration options. We conducted a cross-sectional survey of patients receiving pegfilgrastim and physicians prescribing pegfilgrastim. Respondents' preferences for pegfilgrastim administration options were elicited using direct elicitation; the relative importance of features associated with the options was estimated in a point-allocation exercise. Physicians considered two hypothetical patient profiles when completing the exercises. The samples included 200 patients and 200 physicians. Patients generally preferred the administration option with which they had experience. Among patients, 48.5% with previous in-clinic injections 24 hours after chemotherapy preferred this option; 56.8% with previous OBI administration preferred this option. For a clinically compromised patient, 37.5% of physicians preferred an in-clinic injection option; 49.5% preferred the OBI. For a less compromised patient, 55.5% preferred an in-clinic injection option; 28.0% preferred the OBI. Avoiding the need to return to the clinic was chosen most often as the most important treatment feature for patients and physicians. Patients and physicians identified that returning clinic visits for pegfilgrastim administration may be burdensome. A potential solution to mitigate this burden is the OBI, which allows adherence to the labeled use of pegfilgrastim without return visits to the clinic.

Safety and efficacy of same-day administration of pegfilgrastim in patients (pts) receiving chemotherapy for gastrointestinal (GI) malignancies.

10112 Background: Pegfilgrastim is typically administered 24 hours after chemotherapy per package insert; however some pts are unable or unwilling to return for this additional visit due to work or transportation especially with regimens consisting of infusional 5-FU. Same-day dosing eliminates need for this additional visit. Results from prior studies in other tumor types are inconclusive as few support same-day dosing whereas others show inferiority. Purpose of our study was to determine safety and efficacy of administering pegfilgrastim on same day as chemotherapy in pts with GI malignancies. Methods: A single-institution retrospective review was conducted of pts with GI malignancies who received chemotherapy and same-day pegfilgrastim (6 mg) within 1 hour of completion of chemotherapy from Jan 2014 through Jan 2017. Decision to administer pegfilgrastim was based on NCCN or ASCO recommendations. As per institutional guidelines, pts were counseled on risks of same-day pegfilgrastim prior to its administration. Data was collected on demographics, clinic notes and complete blood counts. Analyses included neutropenia, febrile neutropenia, hospitalization, use of antibiotics or bone pain. Results: A total of 536 chemotherapy cycles in 69 pts were analyzed. Median age was 60 years (range 32-87) with 46% of pts ≥ 65. Pts had an average of 4 risk factors for febrile neutropenia: advanced disease, gender, age &gt; 65 and chemotherapy regimen. Most common malignancy was colon (48%), pancreas (17%) and gastric (17%). Most commonly used regimens included mFOLFOX6 (42%), FOLFIRINOX (23%) and FOLFIRI (12%). Median absolute neutrophil count nadir for all cycles was 4538/uL (range: 1160-25168). Grade 1 and 2 neutropenia developed in 6 of 536 (1%) cycles. Bone pain reported in 3 pts (4%). There were no episodes of grade 3 or 4 neutropenia or febrile neutropenia. None had dose reductions, chemotherapy delays, hospitalizations, or antibiotic use due to neutropenia. Conclusions: We believe our study is the first in GI malignancies to report that same-day pegfilgrastim administration may be as effective and safe as next-day administration, benefiting pts and might reduce costs.