Risk of chemotherapy-induced febrile neutropenia by day of pegfilgrastim prophylaxis in US clinical practice from 2010 to 2015

Objective: Pegfilgrastim prophylaxis (PP) is recommended 1–3 days following administration of chemotherapy during the cycle. Some patients, however, receive PP before or after the recommended timing. While evidence suggests that risk of febrile neutropenia (FN) may be lower when PP is administered per recommendation, such evidence is based on older data. We undertook a new study to compare FN risk between patients who received PP on the last day of chemotherapy (“day 0”) or 4–5 days following chemotherapy (“days 4–5”), versus 1–3 days following chemotherapy (“days 1–3”), using recent data from US clinical practice.

Methods: A retrospective cohort design and data from two US private healthcare claims repositories (2010–2016) were employed. Patients received intermediate/high-risk chemotherapy regimens for solid tumors or non-Hodgkin’s lymphoma, and PP in ≥1 cycle; all cycles with PP were pooled for analyses. Adjusted odds ratios (OR) for FN during the cycle were estimated for patients who received PP on day 0 or days 4–5, vs. days 1–3, using generalized estimating equations.

Results: The study population included 53,814 patients who received PP in 217,273 cycles; in 9% of cycles, patients received PP on day 0 (8%) or days 4–5 (<1%). Odds of FN in cycle 1 were significantly higher among patients receiving PP on day 0 (OR: 1.4 [95% CI: 1.2–1.7]) or days 4–5 (1.9 [1.2–3.0]), vs. days 1–3, in that cycle. Results for subsequent cycles of chemotherapy were comparable to those for the first cycle.

Conclusions: In this large-scale retrospective evaluation of cancer chemotherapy patients receiving PP in recent US clinical practice, PP was administered before or after the recommended timing in 9% of cycles. FN incidence was significantly higher in these cycles providing additional real-world evidence that PP should be administered the day after chemotherapy in alignment with recently updated US practice guidelines.     

Risk of chemotherapy-induced febrile neutropenia with early discontinuation of pegfilgrastim prophylaxis based on real-world data from 2010 to 2015

Objective: Evidence suggests that not all cancer chemotherapy patients who receive first-cycle pegfilgrastim prophylaxis (PP) continue to receive it in later cycles, and that these patients may be subsequently at higher risk of febrile neutropenia (FN). Available evidence, however, may not be reflective of current clinical practice. We undertook an evaluation to estimate the odds of FN, beginning with second chemotherapy cycle, among patients who received PP in that cycle and all previous cycles versus those who received PP in all previous cycles only, using recent real-world data.

Methods: A matched-cohort design and data from two US healthcare claims repositories (2010–2015) were employed. The source population comprised cancer patients who received intermediate/high-risk chemotherapy and first-cycle PP. From the source population, beginning with the second cycle, all patients who received PP in all previous cycles were identified. From this subset, patients who did not receive PP in the cycle of interest (“comparison patients”) were matched to those who received PP in that cycle (“PP patients”); the same process was repeated for subsequent cycles. Odds ratios (ORs) for FN (broad and narrow definitions) were estimated using generalized estimating equations.

Results: Among 47,254 patients in the source population, 9% did not receive second-cycle PP and were matched to those who did. FN odds in cycle 2 were significantly higher among comparison patients versus PP patients (OR [broad definition]: 1.7, p?p?p?p?Conclusions: In this real-world evaluation of cancer chemotherapy patients who received first-cycle PP, FN risk was substantially higher among patients who did not receive PP in subsequent cycles versus those who continued PP.     

The efficiency of granulocyte colony-stimulating factor in hemorrhagic mucositis and febrile neutropenia resulted from methotrexate toxicity

Methotrexate (MTX) remains one of the most frequently used anti-metabolite agents in dermatology. MTX is an analog of folate that competitively and irreversibly inhibits dihydrofolate reductase. Oral mucositis is a common side effect of chemotherapy drugs and is characterized by erythema, pain, poor oral intake, pseudomembranous destruction, open ulceration and hemorrhage of the oral mucosa. In this paper, we report a 32-year-old female with a case of mucositis due to MTX intoxication that resulted from an overdose for rheumatoid arthritis. The patient had abdominal pain, vomiting, and nausea. During follow-up, the patient’s white blood cell count was found to be 0.9?×?10⁹/L (4–10?×?10⁹/L). The patient developed fever exceeding 40?°C. The patient was consulted to the hematology service. They suggested using granulocyte colony-stimulating factor for febrile neutropenia. On the fifth day of treatment, the white blood cell count reached 5.3?×?10⁹/L and the patient’s fever and mucositis started to resolve. Here, we presented a case of hemorrhagic mucositis and febrile neutropenia resulted from high-dose MTX that responded very well to granulocyte colony-stimulating factor treatment and we reviewed the literature.     

Risk of chemotherapy-induced febrile neutropenia with same-day versus next-day pegfilgrastim prophylaxis among patients aged ≥65 years: a retrospective evaluation using Medicare claims

Background: Two recent evaluations reported that risk of febrile neutropenia (FN) may be higher when pegfilgrastim prophylaxis (PP) is administered on same day as chemotherapy rather than per recommendation (1–3 days following chemotherapy). Such evidence is based largely on the experience of younger privately insured adults and may not be generalizable to older patients in US clinical practice.

Methods: A retrospective cohort design and data from Medicare Claims Research Identifiable Files (January 2008–September 2015) were employed. Patients were aged ≥65 years, had breast cancer or non-Hodgkin’s lymphoma, received chemotherapy with intermediate/high risk for FN, and received PP in ≥1 cycle; cycles with PP were stratified based on administration day (same-day [“Day 0”] vs. 1–3 days following chemotherapy [“Days 1–3”]) and were pooled for analyses. Adjusted odds ratios (ORs) for FN during the cycle were estimated for patients who received PP on Day 0 versus Days 1–3.

Results: Study population included 65,003 patients who received PP in 261,184 cycles; in 5% of cycles, patients received PP on Day 0. Incidence proportion for FN in cycle 1 was 11.4% for Day 0 versus 8.4% for Days 1–3; adjusted OR was 1.4 (p?p?p?p?Conclusions: Among Medicare patients receiving chemotherapy and PP in US clinical practice, PP was administered before the recommended timing in 5% of cycles and FN incidence was significantly higher in these cycles. Along with prior research, study findings support recently updated US practice guidelines indicating that PP should be administered the day after chemotherapy.     

Risk of chemotherapy-induced febrile neutropenia with early discontinuation of pegfilgrastim prophylaxis: a retrospective evaluation using Medicare claims

Background: Two recent evaluations reported that many cancer chemotherapy patients discontinue pegfilgrastim prophylaxis (PP) following the first cycle, and that these patients have a higher subsequent risk of febrile neutropenia (FN). Such evidence is based principally on the experience of younger adults with private healthcare coverage, and the generalizability of results to elderly Medicare patients is unknown.

Methods: A matched-cohort design and data from the Medicare Claims Research Identifiable Files were employed. The source population comprised cancer patients aged ≥65 years who received chemotherapy with intermediate/high-risk for FN and first-cycle PP. From the source population, beginning with the second cycle, all patients who received PP in all previous cycles were identified. From this sub-set, patients who did not receive PP in the cycle of interest (“comparison patients”) were matched to those who received PP in that cycle (“PP patients”); the same process was repeated for subsequent cycles. Odds ratios (OR) for FN (broad and narrow definitions) were estimated using generalized estimating equations.

Results: Among 77,616 elderly patients in the source population, 5.3% did not receive second-cycle PP and were matched to those who did. In cycle 2, FN odds were significantly higher among comparison patients vs PP patients when employing the broad definition (OR?=?1.9, p?<?.001) and the narrow definition (OR?=?2.1, p?<?.001). Results for subsequent cycles (broad definition: OR?=?2.0, p?<?.001; narrow definition: OR?=?2.1, p?<?.001) and for the last cycle (broad definition: OR?=?1.4, p?=?.060; narrow definition: OR?=?1.7, p?=?.055) were largely comparable.

Conclusions: In this large-scale evaluation of elderly Medicare patients who received myelosuppressive chemotherapy and first-cycle PP in recent US clinical practice, FN risk was substantially lower among patients who continued to receive PP in subsequent cycles vs those who discontinued PP.     

Risks and consequences of travel burden on prophylactic granulocyte colony-stimulating factor administration and incidence of febrile neutropenia in an aged Medicare population

Objective: Granulocyte colony-stimulating factors (G-CSFs) decrease the incidence of febrile neutropenia (FN) in patients receiving myelosuppressive chemotherapy. This study examines the impact patient travel burden has on administration of prophylactic G-CSFs and the subsequent impact on FN incidence.

Methods: Medicare claims data were used to identify a cohort of beneficiaries age 65+ with non-myeloid cancers at high risk for FN between January 2012 and December 2014. Driving distance and time were calculated from patient residence ZIP code to the location of G-CSF and/or chemotherapy administration. Regression models were used to estimate the odds of G-CSF prophylaxis relative to patient driving distance and time, and odds of FN incidence relative to timing of G-CSF administration (optimal [days 2–4 after chemotherapy], sub-optimal [same day], or none).

Results: The 52,389 study patients had a mean age of 73.5 years, and were 82% female and 89% white race; 49% had female breast cancer, 12% lung cancer, 15% ovarian cancer, and 24% non-Hodgkin’s lymphoma. Of these high FN risk patients, 69% had at least one prophylactic G-CSF administration within at least one chemotherapy cycle. The percentage of patients receiving prophylactic G-CSFs in the first cycle was 56%. Median travel time was slightly longer for patients who did not receive G-CSFs and patients receiving short-acting vs long-acting G-CSFs. The odds of receiving no G-CSFs were 26–52% higher (depending on cancer type) for patients with a?>80-min one-way travel time, compared to patients traveling <20-min. Concurrently, the odds of FN (using a “narrow” definition) were 18–93% higher for patients who did not receive G-CSFs in the first cycle of chemotherapy.

Conclusions: Travel burden, linked to clinic visits for G-CSF administration following myelosuppressive chemotherapy, is associated with sub-optimal use of G-CSF prophylaxis, which may result in a higher incidence of FN.     

G-CSF as prophylaxis of febrile neutropenia in SCLC

ObjectivesIn 1991, small cell lung cancer (SCLC) was reported as the first tumour type where colony stimulating factor (CSF) support was clinically effective. We reviewed 13 health services research studies that addressed CSF use as supportive care for SCLC.MethodsFindings from American Society of Clinical Oncology (ASCO) membership surveys, patterns of care studies, ASCO evidence-based guidelines and cost-effectiveness studies for CSF use were reviewed.ResultsFor primary prophylaxis for SCLC, ASCO CSF clinical guidelines clearly do not support granulocyte (G)-CSF use. Cost-effectiveness models indicate that CSF use in this setting is associated with as much as US$1900 incremental patient care costs per cycle given an 18% febrile neutropenia rate. ASCO membership surveys found that < 10% of respondents supported CSF as primary prophylaxis while a patterns-of-care study found 55% use. In the secondary prophylaxis setting, ASCO CSF guidelines in 1994, 1996 and 1997 were equally supportive of CSF use versus dose reduction but dose-reduction was considered the preferred option in 2000. Over half of the ASCO member respondents in 1994 and in 1997 supported G-CSF use; cost-effectiveness models indicated that CSF use incurred an additional US$144 and 277 per cycle and the patterns of care study found 27% use of CSF in the community practice setting.ConclusionsIn 2002, the findings of a decade of health services studies have shifted towards not being supportive of CSF use for primary or secondary prophylaxis for SCLC patients.     

Travel burden associated with granulocyte colony-stimulating factor administration in a Medicare aged population: a geospatial analysis

Objective: Prophylaxis with granulocyte colony-stimulating factors (G-CSFs) is recommended for patients receiving myelosuppressive chemotherapy regimens with a high risk of febrile neutropenia (FN). G-CSFs should be administered starting the day after chemotherapy, necessitating return trips to the oncology clinic at the end of each cycle. We examined the travel burden related to prophylactic G-CSF injections after chemotherapy in the US.

Methods: We used 2012–2014 Medicare claims data to identify a national cohort of beneficiaries age 65+ with non-myeloid cancers who received both chemotherapy and prophylactic G-CSFs. Patient travel origin was based on residence ZIP code. Oncologist practice locations and hospital addresses were obtained from the Medicare Physician Compare and Hospital Compare websites and geocoded using the Google Maps Application Programming Interface (API). Driving distance and time to the care site from each patient ZIP code tabulation area (ZCTA) were calculated using Open Street Maps road networks. Geographic and socio-economic characteristics of each ZCTA from the US Census Bureau’s American Community Survey were used to stratify and analyze travel estimates.

Results: The mean one-way driving distance to the G-CSF provider was 23.8 (SD 30.1) miles and the mean one-way driving time was 33.3 (SD 37.8) minutes. When stratified by population density, the mean one-way travel time varied from 12.1 (SD 10.1) minutes in Very Dense Urban areas to 76.7 (SD 72.1) minutes in Super Rural areas. About 48% of patients had one-way travel times of <20?minutes, but 19% of patients traveled ≥50?minutes one way for G-CSF prophylaxis. Patients in areas with above average concentrations of aged, poor or disabled residents were more likely to experience longer travel.

Conclusions: Administration of G-CSF therapy after chemotherapy can present a significant travel burden for cancer patients. Technological improvements in the form and methods of drug delivery for G-CSFs might significantly reduce this travel burden.     

Population pharmacokinetics of itraconazole solution used as prophylaxis for febrile neutropenia

Although administration of antifungal agents, such as itraconazole (ITC) solution, for prophylaxis is the most promising strategy for the treatment of haematological malignancies, little is known about the population pharmacokinetic (PK) parameters. A clinical study was conducted to identify PK parameters for the administration of 200 mg/day ITC solution used as prophylaxis for febrile neutropenia in patients undergoing treatment. The study population comprised six patients. NONMEM software was used to estimate PK parameters. Clearance, volume of distribution and the absorption rate constant were 12.7 L/h, 333 L and 1.72 h⁻¹, respectively. These parameters were different from a previous study to large extent, which may be due to differences in intended patients. These differences strongly suggest that establishment of population pharmacokinetics is essential for planning a prospective clinical trial. Assuming a normal distribution, we predicted the trough concentrations of 94.5% of the patients receiving 200 mg/day ITC solution to be >250 ng/mL, indicating that administration of 200 mg/day might be suitable for prophylaxis. This pilot study presents a basic PK model of ITC solution in Japanese haematological patients for the establishment of optimal administration. Large-scale studies will be necessary in the future to determine population PK parameters with covariates.     

Prophylaxis of febrile neutropenia with colony-stimulating factors: the first 25 years

Abstract

Filgrastim prophylaxis, both primary and secondary, was rapidly incorporated into clinical practice in the 1990s. When pegfilgrastim became available in 2002, it quickly replaced filgrastim as the colony-stimulating factor (CSF) of choice for prophylaxis. Use of prophylaxis increased markedly in the first decade of this century and has stabilized during the present decade. Data concerning real-world CSF prophylactic practice patterns are limited but suggest that both primary and secondary prophylaxis are common, and that use is frequently inappropriate according to guidelines. The extent of inappropriate use is controversial, as are issues concerning the cost-effectiveness of prophylaxis versus no prophylaxis and the cost-effectiveness of primary prophylaxis versus secondary prophylaxis. Nevertheless, CSF prophylaxis is firmly established as a valuable adjunct to chemotherapy and will almost certainly continue to be widely used for the foreseeable future. In this article, we chronicle the use and impact of CSF prophylaxis in US patients receiving myelosuppressive chemotherapy for non-myeloid malignancies. We emphasize the interplay of expert opinion, clinical evidence, and economic factors in shaping the use of CSFs in clinical practice over time, and, with the recent introduction of new CSF agents and options, we aim to provide useful clinical and economic information for healthcare decision makers.     

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

Abstract

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.     

聚乙二醇重组人粒细胞集落刺激因子对猕猴辐射致粒细胞减少症的治疗作用

目的研究聚乙二醇重组人粒细胞集落刺激因子(PEG-rhGCSF)对猕猴辐射致粒细胞减少症的治疗作用。方法正常雄性猕猴全身一次性双侧照射60Coγ3.0 Gy,24 h后一次性sc给予PEG-rhGCSF 30,100和300μg·kg-1,及连续10 d rhGCSF 10μg·kg-1。检测50 d内的外周血象和骨髓造血细胞的情况。结果猕猴接受照射后,外周血白细胞及绝对中性粒细胞(ANC)迅速下降,造成粒细胞减少症。给药后1 d,PEG-rhGCSF治疗组均出现一过性ANC动员峰,且峰值与剂量呈正相关。PEG-rhGCSF可延缓ANC达谷时间且可以提高谷水平。与照射模型组的(7.2±2.5)d相比,PEG-rhGCSF 30,100和300μg·kg-1组抗生素需求天数3.2±2.9,1.4±1.9和(0.2±0.4)d明显缩短(P<0.05);与rhGCSF组粒细胞减少症持续时间(28±7)d相比,PEG-rhGCSF 100和300μg·kg-1组分别为(19±14)d与(7±6)d显著缩短(P<0.01)。连续注射rhGCSF 10 d与单次注射PEG-rhGCSF的药效作用相当。结论 PEG-rhGCSF对猕猴辐射致粒细胞减少症有明显治疗作用,可促进骨髓粒系增殖、分化成熟以及释放,恢复造血功能。治疗作用呈良好量效关系,与rhGCSF相比具有明显长效作用。     

国产与进口重组人粒细胞集落刺激因子治疗化疗后中性粒细胞减少比较

目的 :比较国产和进口重组人粒细胞集落刺激因子 (rhG_CSF)治疗成人血液恶性肿瘤化疗后的中性粒细胞减少。方法 :对血液恶性肿瘤化疗后中性粒细胞减少的病人用rhG_CSF治疗 ,一组使用国产rhG_CSF(男性 39例次 ,女性 30例次 ,年龄 41a±s 17a) ,另一组使用进口rhG_CSF(男性 33例次 ,女性 2 4例次 ,年龄 42a± 17a) ,剂量均为 15 0～ 30 0 μg/d ,qd ,10～ 14d为一个疗程。结果 :国产rhG_CSF与进口同类产品总有效率分别为 97%和98% ,中性粒细胞恢复正常所需的时间为 7d± 3d和 8d± 3d ;感染发热的发生率 (T >38℃ ) 2组分别为 2 2 %和 2 5 % ;抗生素平均使用日数为 7.8d± 2 .5d和 8.5d± 2 .6d。2组差异无显著意义 (P >0 .0 5 )。结论 :国产和进口rhG_CSF均能缩短化疗后的骨髓抑制期 ,促进中性粒细胞的恢复 ,减少严重感染的发生率 ,国产品疗效和安全性与进口品相似     

注射用聚乙二醇化重组人粒细胞集落刺激因子Ⅰ期临床试验

目的:评价北京双鹭药业股份有限公司研制的注射用聚乙二醇化重组人粒细胞集落刺激因子(PEG-rhG-CSF)用于预防化疗引起的中性粒细胞减少症的安全性,观察其升高外周血中性粒细胞和CD3+4细胞的效果,探讨量效关系,并通过人体药代动力学试验了解该药在人体内的吸收、分布和消除规律,为制定II期临床研究给药方案提供依据。方法:作为开放性试验,受试者均为初治的恶性肿瘤患者,连续接受两个周期紫杉醇联合卡铂方案化疗,第1周期为对照周期,第2周期化疗药物给药结束48 h给予PEG-rhG-CSF;其初始剂量为30μg.kg-1,递增剂量依次为60,100,150和200μg.kg-1。结果:共入组34例患者,30例可评价疗效和安全性。与PEG-rhG-CSF相关的不良反应仅观察到I～II度躯干及四肢的肌肉关节痛(8/30)。较之对照周期,应用PEG-rhG-CSF周期,化疗期间IV度中性粒细胞绝对值(ANC)减少症的发生率明显减少,且ANC随研究时间呈双峰改变,外周血ANC最低值前移,并明显提高;其最低值及第二峰的峰值变化,呈一定程度的量效关系。结论:本项研究中PEG-rhG-CSF表现出良好的耐受性,未见到剂量限制性毒性剂量,也未达到最大耐受剂量。鉴于其疗效已满足临床需要,推荐PEG-rhG-CSF II期临床试验研究的用药剂量为60和100μg.kg-1。     

The effect of granulocyte colony-stimulating factor administration on carbon monoxide neurotoxicity in rats

Granulocyte colony-stimulating factor (G-CSF) is considered to be a novel neuroprotective agent. Beneficial effects have been demonstrated by administrating G-CSF in different experimental stroke models. In this study, we evaluated the efficacy of G-CSF therapy on carbon monoxide (CO) neurotoxicity in rats exposed to acute CO poisoning. Immediately after exposure to 3,000 ppm of CO for 60 minutes, 50, 100, and 150 µg/kg of G-CSF or normal saline were administered to rats. Rats were sacrificed after 24 hours for serum marker analysis or 1 week for histopathological examination. Brain sections were stained with hematoxylin and eosin to assess leukocyte infiltration and hippocampal injury and with Luxol fast blue to assess demyelination. S100β and glial fibrillary acidic protein (GFAP) serum levels were evaluated by commercial enzyme-linked immunosorbent assay kits. According to histopathological findings, G-CSF administration significantly restricted white-matter demyelination (150 µg/kg) (P = 0.006). Also, serum levels of S100β in G-CSF-treated groups (100 and 150 µg/kg) decreased significantly (P < 0.01and P < 0.05, respectively). In all does, G-CSF significantly reduced serum levels of GFAP (P < 0.01 for 50 µg/kg and P < 0.001 for other doses). Administration of G-CSF after CO poisoning attenuates brain cell damage through remyelination. G-CSF also decreases levels of related biomarkers, such as S100β and GFAP.     

粒细胞集落刺激因子治疗肾移植后白细胞减少症

目的：评价重组人粒细胞集落刺激因子（Ｇ＿ＣＳＦ）在治疗肾移植后白细胞减少症中的效果及安全性。方法：应用Ｇ＿ＣＳＦ治疗肾移植后白细胞减少症１０例（男性６例，女性４例，年龄３８±ｓ１１ａ），每例注射Ｇ＿ＣＳＦ１５０μｇ，ｓｃ，ｑｄ，直至白细胞计数＞４×１０９／Ｌ。结果：１０例接受Ｇ＿ＣＳＦ的剂量为２２５±１０６μｇ，治疗前白细胞计数基值为（２．２±０．４）×１０９／Ｌ，治疗后白细胞峰值为（１０．６±２．６）×１０９／Ｌ（Ｐ＜０．０１），开始治疗至出现峰值时间为３．６±１．３ｄ，治疗前血清肌酐为２３５±１３５μｍｏｌ／Ｌ，治疗后２ｗｋ内最高血清肌酐为２３４±１２５μｍｏｌ／Ｌ（Ｐ＞０．０５）。结论：Ｇ＿ＣＳＦ治疗肾移植后白细胞减少症疗效显著，且不引起排斥反应     

粒细胞集落刺激因子抗感染及抑制一氧化氮的性质

A proposed scheme between the possibleinteractions of pro- and anti-inflammatory cytokines,NO and G-CSF during severe inflammation/infection ispresented. Taken together, these data indicate that G-CSF exhibits anti-inflammatory properties which mayprove to be beneficial in situations associated with anincreased activity of the cellular immune system.Since the suppressive effects of G-CSF on theproduction of pro-inflammatory mediators like "FNF-αand nitric oxide are most likely neither cell type nor     

Comparison of pegfilgrastim with filgrastim on febrile neutropenia,grade IV neutropenia and bone pain: a meta-analysis of randomized controlled trials

ABSTRACT

Background and objective: While head-to-head clinical trials demonstrate pegfilgrastim to be as efficacious as filgrastim in reducing chemotherapy-induced neutropenia, these studies lacked the statistical power to demonstrate better outcomes with one therapy compared to the other. Our objective was to obtain a pooled estimate of the effect of pegfilgrastim compared with filgrastim on incidence of febrile neutropenia (FN), and related outcomes among patients with solid tumors and malignant lymphomas receiving myelosuppressive chemotherapy.

Research design and methods: We searched PubMed and EMBASE for articles published from January 1, 1990 to August 31, 2006 reporting on randomized controlled trials (RCTs) that compared the efficacy and safety of pegfilgrastim versus filgrastim. We only accepted studies in which filgrastim (5 µg/kg/day) and pegfilgrastim (100 µg/kg or a fixed dose of 6?mg) were administered at approved doses indicated on the package insert. Pooled relative risk (RR) was estimated using the conservative random effects, empirical Bayesian method of Hedges and Olkin.

Main outcome measures: Rates of grade IV neutropenia and of FN, time to absolute neutrophil count (ANC) recovery, and bone pain.

Results: We identified five RCTs, with a total of 617 patients, evaluating the efficacy of a single dose of pegfilgrastim per cycle versus daily filgrastim injections. Although only one study had a statistically significant difference in FN reductions favoring pegfilgrastim over filgrastim (relative risk reduction of 50%; p = 0.027), the pooled RR showed a statistically significant favorable result for pegfilgrastim (RR = 0.64; 95% CI, 0.43–0.97). Grade IV neutropenia rates (for cycle 1: RR = 0.99; 95% CI, 0.91–1.08; cycle 2: RR = 0.88; 95% CI, 0.70–1.11; cycle 3: RR = 0.80; 95% CI, 0.47–1.36; cycle 4: RR = 0.90; 95% CI, 0.71–1.13), time to ANC (SMD = 0.11, 95% CI, –0.34–0.56), and incidence of bone pain (RR = 0.95; 95% CI, 0.76–1.19) were similar between the two G?CSFs. The included trials varied in the type of cancer, chemotherapy regimen and type of trial.

Conclusion: A single dose of pegfilgrastim performed better than a median of 10–14 days of filgrastim in reducing FN rates for patients undergoing myelosuppressive chemotherapy.     

The use and effectiveness of granulocyte colony-stimulating factor in primary prophylaxis for febrile neutropenia in the outpatient setting.

OBJECTIVES: To conduct a drug utilization review (DUR) on the use of granulocyte colony-stimulating factor (G-CSF) and to study the effectiveness of this agent in preventing the incidence of febrile neutropenia (FN). METHODS: Outpatients to whom G-CSF was dispensed were identified and their actual medical records were reviewed to verify patients who received G-CSF for primary prophylaxis. Literature was reviewed to determine the expected incidence and risk of FN for chemotherapy regimens used, and the compliance of prescribers with the institutional guidelines was evaluated. After that, the proportion of patients who developed FN was identified and compared to the expected incidence from literature. Data analysis was performed on the outcome of patient-cycle. RESULTS: Of the 99 patient-cycles, 53 (53%) were compliant with guidelines whereas 46 (47%) were not. FN developed in 12 (12.1%, 95% CI = 5.7, 18.5) while the expected average incidence of FN was 32.7%. Eleven (21%, 95% CI = 10.1, 32.2) of the 53 patient-cycles that were compliant with guidelines developed FN, whereas one patient among the non-compliant group developed FN (2%, 95% CI = 0.0, 6.2). The expected incidence of FN was 42.9 and 21.5%, in the compliant group, and noncompliant group, respectively. Based on expected FN rates, the respective reduction in the incidence of FN was 51, and 90%. CONCLUSIONS: Lack of adherence to institutional guidelines was noticed in G-CSF prescribing. Reasons behind poor compliance with the guidelines must be verified and resolved. Prophylactic G-CSF is effective in reducing the incidence of FN; however, further research in a larger population is warranted to confirm these findings.