Prevention Of Chemotherapy-induced Febrile Neutropenia Research Articles

Eflapegrastim (Rolvedon) for prevention of chemotherapy-induced febrile neutropenia.

Eflapegrastim-xnst (Rolvedon [Spectrum]; previously called Rolontis), a granulocyte colony-stimulating factor (G-CSF) conjugated to an Fc fragment of human IgG4, has been approved by the FDA to decrease the incidence of infection, as manifested by febrile neutropenia, in adults with nonmyeloid malignancies receiving myelosuppressive chemotherapy that can cause clinically significant febrile neutropenia.

Cost-effectiveness of pegfilgrastim versus filgrastim for prevention of chemotherapy-induced febrile neutropenia in patients with lymphoma: a systematic review

BackgroundFebrile neutropenia (FN) is a prevalent and potentially life-threatening complication in patients with lymphoma receiving myelosuppressive chemotherapy. Pegfilgrastim is more effective than filgrastim as prophylaxis for FN. However, its usage has been limited because of its higher cost. Pegfilgrastim’s value for money remains unclear.ObjectiveTo systematically review the cost-effectiveness of pegfilgrastim compared to filgrastim as a primary or secondary prophylaxis for chemotherapy-induced FN among patients with lymphoma.MethodsA systematic literature search was conducted in PubMed, EMBASE, Cochrane Library databases, and Google Scholar. The most widely used economic evaluations (cost-effectiveness analysis, cost-utility analysis and cost-benefit analysis) were included in the review. Data extraction was guided by the Consolidated Health Economic Evaluation Reporting Standards checklist, and the quality of reviewed articles was assessed using the Joanna Briggs Institute (JBI) checklist. Cost-effectiveness data were rigorously summarized and synthesized narratively. Costs were adjusted to US$ 2020.ResultsWe identified eight economic evaluation studies (two cost-utility analyses, three cost-effectiveness analyses, and three studies reporting both cost-effectiveness and cost-utility analyses). Half of these studies were from Europe (n = 4), the other half were from Iran, USA, Canada, and Singapore. Six studies met > 80% of the JBI quality assessment criteria. Cost-effectiveness estimates in the majority (n = 6) of these studies were for Non-Hodgkin Lymphoma patients receiving myelosuppressive chemotherapy with high-risk of FN (> 20%). The studies considered a wide range of baseline FN risk (17–97.4%) and mortality rates (5.8–8.9%). Reported incremental cost-effectiveness ratios ranged from US$ 2199 to US$ 8,871,600 per quality-adjusted life-year (QALY) gained, dominant to US$ 44,358 per FN averted, and US$ 4261- US$ 7251 per life-years gained. The most influential parameters were medication and hospitalization costs, the relative risk of FN, and assumptions of mortality benefit.ConclusionsMost studies showed that pegfilgrastim is cost-effective compared to filgrastim as primary and secondary prophylaxis for chemotherapy-induced FN among patients with lymphoma at a cost-effectiveness threshold of US$ 50,000 per QALY gained. The findings could assist clinicians and healthcare decision-makers to make informed decisions regarding resource allocation for the management of chemotherapy-induced FN in settings similar to those studied.

Efficacy of same-day versus next-day administration of pegfilgrastim for the prevention of chemotherapy-induced febrile neutropenia in breast cancer patients receiving dose-dense doxorubicin and cyclophosphamide: A retrospective multi-site analysis.

Administering pegfilgrastim on the same day as chemotherapy can improve patient satisfaction through convenience and may increase the utilization of cost-effective biosimilars compared to next-day administration, but the effect on clinical outcomes with commonly used breast cancer regimens is unclear. This multi-site, retrospective cohort study included breast cancer patients age 18 years or older who received dose-dense doxorubicin and cyclophosphamide (ddAC) and pegfilgrastim between 1 June 2016 and 31 May 2020. Pegfilgrastim was given on the same day as chemotherapy at one site and the day after chemotherapy at the other two sites. The primary endpoint compared the incidence of febrile neutropenia associated with pegfilgrastim administration timing. A total of 360 patients were reviewed (146 same-day administration and 214 next-day administration). In the same-day group 36 patients (24.6%) developed FN compared to 25 patients (11.7%) in the next-day group (p = 0.002). Same-day administration also significantly increased the incidences of additional acute care visits (11.6% vs 2.8%, p = 0.0016), grade ≥ 3 neutropenia (38.4% vs 13.6%, p < 0.0001), chemotherapy dose reductions (21.2% vs 6.1%, p < 0.0001), and antibiotic use (26.7% vs 12.6%, p = 0.001). Same-day administration did not significantly increase the rate of hospitalization (15% vs 11.2%, p = 0.36) and delay of next chemotherapy cycle by ≥1 day (8.2% vs 6.1%, p = 0.57) due to neutropenic complications. Administering pegfilgrastim on the same day as ddAC led to a significant increase in neutropenic complications. This study confirms the need to administer pegfilgrastim the day after chemotherapy in breast cancer patients receiving ddAC.

Supportive therapies in the prevention of chemotherapy-induced febrile neutropenia and appropriate use of granulocyte colony-stimulating factors: a Delphi consensus statement

PurposeData indicate that the use of prophylactic granulocyte colony-stimulating factors (G-CSFs) for chemotherapy-induced febrile neutropenia (FN) in routine practice is not consistent with guideline recommendations. The initiative “supportive care for febrile neutropenia prevention and appropriateness of G-CFS use” was undertaken to address the issue of inappropriate prescription of G-CSFs and to improve guideline adherence in the treatment of FN.MethodsIn a two-round Delphi procedure, 36 medical oncologists reviewed clinically relevant recommendations on risk assessment, the appropriate use of G-CSFs, and the prevention of FN based on available literature and individual clinical expertise.ResultsThe consensus was reached on 16 out of 38 recommendations, which are backed by evidence from randomised clinical trials and routine clinical practice. The medical oncologists agreed that the severity of neutropenia depends on patients’ characteristics and chemotherapy intensity, and therefore, the risk of severe neutropenia or FN should be assessed at each chemotherapy cycle so as to initiate prophylaxis with G-CSFs if required. The use of biosimilar G-CSFs, with similar efficacy and safety profiles to the originator biologic, has improved the availability and sustainability of cancer care. The timing of supportive therapy is crucial; for example, long-acting G-CSF should be administered 24–72 h after chemotherapy administration. Each biological agent has a recommended administration dose and duration, and it is important to follow these recommendations to avoid complications associated with under-prophylaxis.ConclusionIt is hoped that these statements will help to increase adherence to guideline recommendations for appropriate G-CSF use and improve patient care.

Evaluating the safety and effectiveness of PegaGen® (pegfilgrastim) for the prevention of chemotherapy-induced febrile neutropenia: a post-marketing surveillance study.

Phase IV clinical trials are required to evaluate the real-world safety and effectiveness of drugs. This study aimed to evaluate the safety and effectiveness of once-per-cycle administration of PegaGen® (pegfilgrastim, CinnaGen, Iran) in cancer patients. In this open-label, multicenter, prospective, real-world, post-marketing surveillance study, patients with any type of cancer receiving chemotherapy regimens with a high risk of febrile neutropenia (FN) were included if they were prescribed pegfilgrastim for FN prophylaxis. The primary objective of this study was to assess the safety and the secondary objective was to assess the effectiveness of pegfilgrastim in the prevention of FN in cancer patients. A total of 654 patients (51.73 ± 15.12years of age) were enrolled and 3615 cycles of pegfilgrastim injections were recorded. The most common malignancies among the study patients were breast cancer (n = 192, 29.36%), lymphoma (n = 131, 20.03%), and gastric cancer (n = 65, 9.94%). The median (Q1, Q3) number of pegfilgrastim cycles per patient was 6 (4, 7). A single 6mg dose was injected in 99.17% of the cycles. A total number of 816 adverse events (AEs) were reported in 246 patients (37.62%). Bone pain was recorded in 141 patients (21.56%) and in 440 cycles (12.17%). Among all patients, 45 patients (6.88%) experienced FN 51 times, and FN frequency was 1.4% among cycles. Moreover, 14 (2.14%) patients were hospitalized following FN. Antibiotics were administered to 24 patients (3.67%) for FN treatment. The results from this post-marketing surveillance study support the safety and effectiveness of PegaGen® used for the prevention of chemotherapy-induced FN in patients with various types of cancer and treatment regimens. Clinicaltrials.gov identifier: NCT04460079.

Pegfilgrastim for the prevention of chemotherapy-induced febrile neutropenia in patients with solid tumors

Introduction: Neutropenia and febrile neutropenia are the most common and most severe bone marrow toxicities of chemotherapy. Recombinant granulocyte-colony stimulating factors (G-CSFs), both daily (filgrastim and biosimilars, and lenograstim) and long-acting (pegfilgrastim and lipegfilgrastim) formulations, are currently available to counteract the negative consequences of these side effects.Areas covered: The purpose of this article is to review the physiopathology of chemotherapy-induced febrile neutropenia and its consequences, and the current evidence regarding the pharmacological properties, clinical efficacy and cost-effectiveness of pegfilgrastim as a strategy to prevent chemotherapy-induced febrile neutropenia in patients with solid tumors.Expert opinion: Chemotherapy-induced febrile neutropenia and its complications are still a major health-care concern, and the inappropriate employment of G-CSFs in clinical practice can partially explain its burden. Pegfilgrastim has pharmacological advantages over daily G-CSFs that makes it easily administrable, thus reducing the chance of incorrect delivery. The once-per-cycle administration might explain the findings derived from observational studies suggesting a possible superior efficacy of pegfilgrastim over daily G-CSFs. For patients at higher risk of failure with daily G-CSF prophylaxis (e.g. risk of non-compliance, difficulties on performing regular hemograms, high risk of developing febrile neutropenia), pegfilgrastim might be the most appropriate option.

Myeloid growth factor utilization in a commercial and Medicare population: Phase 1 of a quality improvement initiative.

242 Background: Some clinical practice guidelines encourage the judicial use of myeloid growth factors (MGFs) in the prevention of chemotherapy-induced febrile neutropenia (FN) because of efficacy and safety concerns. For example, the ASCO guidelines state that a dose reduction of myelosuppressive chemotherapy in patients with incurable disease rather than prescribing a MGF for secondary prophylaxis is a reasonable alternative. Because there is wide variation in MGF prescribing, New Century Health (NCH) conducted a quality improvement analysis of MGF requests in a commercial and Medicare population. The objectives are to: (1) describe the cohort demographics, (2) identify areas of improvement to promote cost-effective use, and (3) measure the economic impact from interventions. Methods: MGF authorization requests for oncology indications to NCH in 2013 were analyzed for cohort demographics: age, weight, tumor diagnosis, and treatment intention (e.g., metastatic/palliative, curative, etc.). Requests were analyzed for concurrent use with chemotherapy, approval status of the request (including reason for withdrawal), and cost saving associated with interventions. Results: There were 7,958 requests for a MGF; 81% were for pegfilgrastim and 19% for filgrastim. Average age of the cohort was 66 years, weight-based dosing (&gt;70 kg) was appropriate in 43% of patients receiving 300 mcg and 72% of patients receiving 480 mcg. MGFs were most commonly requested in: breast (18%), lung (17%), lymphoma (14%), and gynecologic (8%) tumors. 40% of requests were for metastatic/recurrent disease and 38% for curative intent. 6,724 (84%) of requests were authorized based on established-use criteria. The main reason for not authorizing was lack of compendia support for both primary and secondary prophylaxis; this resulted in approximately $3.5 million in cost savings. Conclusions: There is opportunity to improve efficiency of MGFs use in this population through a dose rounding protocol and by promoting chemotherapy dose reductions, as advocated by the ASCO guidelines. Further analysis will assess the concordance of MGF use with guidelines, specifically in regard to chemotherapy regimens and their risk of FN.

Rational Development Of Lipegfilgrastim, a Novel Long-Acting Granulocyte Colony-Stimulating Factor, Using Glycopegylation Technology

IntroductionRecombinant human granulocyte colony-stimulating factors (G-CSFs) are indicated for the prevention of chemotherapy-induced febrile neutropenia in patients receiving myelosuppressive chemotherapy. Filgrastim is a 175-amino-acid, short-acting, recombinant methionyl form of human G-CSF (r-metHuG-CSF) with a molecular weight of ∼19 kDa. The addition of polyethylene glycol (PEG) via PEGylation is a well-established technology that improves the physicochemical profile, enhances the solubility, and prolongs the half-life of therapeutic proteins. Pegfilgrastim, a PEGylated version of filgrastim, is currently the only available long-acting G-CSF, requiring fixed-dose subcutaneous (SC) administration only once per chemotherapy cycle. A new long-acting G-CSF, lipegfilgrastim, is under investigation for the prevention of chemotherapy-induced neutropenia. The rational design and development of lipegfilgrastim, and its novel manufacturing process, may provide a valuable fixed-dose, once-per-cycle, alternative long-acting G-CSF option. This analysis compares the design, protein chemistry, and physicochemical properties of lipegfilgrastim and pegfilgrastim, and evaluates the clinical implications of their differences. MethodsThe rational design of lipegfilgrastim focused on refining the PEGylation process. A novel technology platform was developed that enabled selective addition of PEG to a previously enzymatically attached glycan moiety instead of directly to the amino acid (as in standard PEGylation). Sequon scanning was used to scan the G-CSF protein to identify the best sites for glycosylation and glycoPEGylation that would have the least predicted effect on protein biologic activity. In recombinant G-CSF derived from Escherichia coli (E. coli), this was determined to be the single, natural, non-utilized O-glycosylation site. Addition of an O-glycan at this site was achieved by enzymatic activity of a selective, truncated N-acetylgalactosaminyltransferase isoform 2 fused with maltose-binding protein at the threonine residue within the chosen site. A 20-kDa PEG-sialic acid derivative was enzymatically transferred to the O-glycan with a sialyltransferase. Thus, the glycoPEGylation process modified only the O-glycosylation site of the G-CSF protein, resulting in a therapeutic product with an extended half-life. ResultsThe resultant glycoPEGylation product, lipegfilgrastim, is a long-acting, site-specific glycoPEGylated r-metHuG-CSF (molecular weight ∼38 kDa) produced by conjugation of a single 20-kDa PEG to the natural O-glycosylation site of G-CSF expressed in E. coli. In comparison, pegfilgrastim is produced by conjugation of a 20-kDa PEG to the N-terminal of G-CSF expressed in E. coli, and PEGylation results in a heterogeneous product with multiple PEGylated isoforms requiring further purification during the manufacturing process. Potency and receptor-binding studies have shown no apparent difference between lipegfilgrastim and pegfilgrastim (Scheckermann C, 2013, EHA, Abstract P1024). However, glycoPEGylation appears to provide lipegfilgrastim with different pharmacokinetic and pharmacodynamic profiles. In phase I studies in healthy volunteers, lipegfilgrastim 6 mg SC had ∼64% greater cumulative exposure and ∼36% higher peak exposure compared with pegfilgrastim 6 mg SC (Kohler E, 2012, MASCC/ISOO, Abstract A-445-0013-00997). Lipegfilgrastim also had a longer half-life compared with that of pegfilgrastim (geometric means, 32.4 hours vs 27.2 hours, respectively). In a double-blind, randomized, phase III trial, lipegfilgrastim was shown to be noninferior to pegfilgrastim in the duration of severe neutropenia in patients with breast cancer (Udo M, 2012, EHA, Abstract 1375). ConclusionsGlycoPEGylation is an advanced and efficient process that permits the manufacture of a novel, customized, homogenous therapeutic protein, lipegfilgrastim, for the prevention of chemotherapy-induced neutropenia. The manufacturing process is simple, controllable, and scalable. Lipegfilgrastim has an extended half-life, permitting once-per-cycle SC administration and improved bioavailability and exposure and appears to be an effective alternative long-acting G-CSF. Disclosures:Mahlert:Merckle Biotec GmbH (Teva Pharmaceuticals, Inc. Company): Employment. Schmidt:BioGeneriX GmbH (Teva Pharmaceuticals Inc. company): Employment. Allgaier:Merckle GmbH, Ulm, Germany (Teva Pharmaceuticals, Inc. company): Employment. Liu:Teva Pharmaceuticals, Inc: Employment. Müller:Teva Pharmaceuticals, Inc: Employment. Shen:Teva Pharmaceuticals, Inc: Employment.

Primary prophylactic colony-stimulating factors for the prevention of chemotherapy-induced febrile neutropenia in breast cancer patients

High-dose or dose-intensive cytotoxic chemotherapy often causes myelosuppression and severe neutropenia among cancer patients. Severe neutropenia accompanied by fever, named febrile neutropenia (FN), is the most serious manifestation of neutropenia usually requiring hospitalization and intravenous antibiotics. FN and neutropenia can lead to chemotherapy treatment delays or dose reductions, which potentially compromises the effectiveness of cancer treatment and prospects for a cure. Granulocyte-macrophage (GM) and granulocyte colony-stimulating factors (G-CSFs) are administered during chemotherapy in order to prevent or reduce the incidence or the duration of FN and neutropenia. To assess the effect of prophylactic colony-stimulating factors (CSFs) in reducing the incidence and duration of FN, and all-cause and infection-related mortality during chemotherapy in patients with breast cancer. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, HEALTHSTAR, International Health Technology Assessment, SOMED, AMED and BIOSIS up to 8 August 2011. We also searched three Chinese databases (VIP, CNKI, CBM), the metaRegister of Controlled Trials, ClinicalTrials.gov, the World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP) and OpenGrey.eu up to August 2011. Randomized controlled trials (RCTs) comparing CSFs (any dose) with placebo or no treatment in patients with breast cancer at any stage, at risk of developing FN while undergoing any type of chemotherapy. We used pooled risk ratios (RR) with 95% confidence intervals (CIs) for binary outcomes. At least two review authors independently extracted data and assessed the risk of bias of the included studies. Trial authors were contacted for further details when information was unclear. We included eight RCTs involving 2156 participants with different stages of breast cancer and chemotherapy regimens. The trials were carried out between 1995 and 2008 and judged as being at least at moderate risk of bias. The strength of the evidence was weak for the majority of outcomes, which was mostly because of the small numbers of evaluable patients, varying definitions, as well as unclear measurements of the trials' outcomes and uncertain influences of supportive treatments on them. In most trials, the chemotherapy regimens had a risk of FN that was below the threshold at which current guidelines recommend routine primary prophylaxis with CSFs. Using CSFs significantly reduced the proportion of patients with FN (RR 0.27; 95% CI 0.11 to 0.70; number needed to treat for an additional beneficial outcome (NNTB) 12) but there was substantial heterogeneity which can be explained by possible differential effects of G-CSFs and GM-CSFs and different definitions of FN. A significant reduction in early mortality was observed in CSF-treated patients compared to placebo or no treatment (RR 0.32; 95% CI 0.13 to 0.77; NNTB 79). This finding was based on 23 fatal events in 2143 patients; wherein 19 of these 23 events occurred in one study and 17 events were attributed to progression of the disease by the study authors. For infection-related mortality, there were no significant differences between CSF and control groups (RR 0.14; 95% CI 0.02 to 1.29). In CSF-treated patients, the risk for hospitalization was significantly reduced (RR 0.14; 95% CI 0.06 to 0.30; NNTB 13), as well as the use of intravenous antibiotics (RR 0.35; 95% CI 0.22 to 0.55; NNTB 18). The risks of severe neutropenia, infection or not maintaining the scheduled dose of chemotherapy did not differ between CSF-treated and control groups. CSFs frequently led to bone pain (RR 5.88; 95% CI 2.54 to 13.60; number needed to treat for an additional harmful outcome (NNTH) 3) and injection-site reactions (RR 3.59; 95% CI 2.33 to 5.53; NNTH 3). In patients with breast cancer receiving chemotherapy, CSFs have shown evidence of benefit in the prevention of FN. There is evidence, though less reliable, of a decrease of all-cause mortality during chemotherapy and a reduced need for hospital care. No reliable evidence was found for a reduction of infection-related mortality, a higher dose intensity of chemotherapy with CSFs or diminished rates of severe neutropenia and infections. The majority of adverse events reported from CSF use were bone pain and injection-site reactions but no conclusions could be drawn regarding late-term side effects.

Febrile neutropenia: highlighting the role of prophylactic antibiotics and granulocyte colony-stimulating factor during standard dose chemotherapy for solid tumors

The prevention of chemotherapy-induced febrile neutropenia is important as it reduces hospitalization and is likely to improve quality of life. Several prophylactic strategies are available, although their use in patients with an anticipated short duration of neutropenia is controversial and not recommended. This paper presents the results of a review of the literature on the efficacy and cost-effectiveness of prophylactic antibiotics and/or granulocyte colony-stimulating factor, and also discusses the recommendations in current guidelines in view of recent publications. Both primary prophylactic granulocyte colony-stimulating factor and prophylactic antibiotics reduce the risk of febrile neutropenia considerably, and the addition of prophylactic granulocyte colony-stimulating factor to antibiotics is even more effective. As antibiotics, however, give rise to antimicrobial resistance and granulocyte colony-stimulating factor is expensive, tailoring of prophylaxis is clearly needed. This will increase the absolute clinical and economical benefits of prophylaxis. Patient-related, treatment-related and disease-related factors enhancing the risk of febrile neutropenia are discussed, including the, underrated, high risk of febrile neutropenia specifically in the first cycles of chemotherapy. Half of the patients developing febrile neutropenia during treatment do so in the first cycle of chemotherapy, which favors primary prophylaxis. The efficacy of secondary prophylaxis is not well documented. Finally, new interesting agents in the treatment and supportive care of solid tumors have become available, and these are discussed in relation to the incidence and prevention of febrile neutropenia.

Prevention of Chemotherapy-Induced Febrile Neutropenia by Prophylactic Antibiotics Plus or Minus Granulocyte Colony-Stimulating Factor in Small-Cell Lung Cancer: A Dutch Randomized Phase III Study

Febrile neutropenia (FN) is a major complication of chemotherapy. Antibiotics as well as granulocyte colony-stimulating factor (G-CSF) are effective in preventing FN. This multicenter randomized phase III trial determines whether the addition of G-CSF to antibiotic prophylaxis can further reduce the incidence of FN in patients with small-cell lung cancer (SCLC) at the risk of FN. Patients (N = 175) were stratified for stage of disease, performance status, age, and prior chemotherapy treatment, and were randomly assigned for treatment with cyclophosphamide, doxorubicin, and etoposide (CDE), followed by prophylactic antibiotics alone (ciprofloxacin and roxithromycin) or by antibiotics in combination with G-CSF on days 4 to 13. In cycle 1, 20 patients (24%) in the antibiotics group developed FN compared with nine patients (10%) in the antibiotics plus G-CSF group (P = .01). In cycles 2 to 5, the incidences of FN were practically the same in both groups (17% v 11%). Only the treatment parameters (odds ratio, 0.33; 95% CI, 0.14 to 0.78) and age (1.067 per year; 95% CI, 1.013 to 1.0124) were related to the probability of FN in cycle 1. Primary G-CSF prophylaxis added to primary antibiotic prophylaxis is effective in reducing FN and infections in SCLC patients at the risk of FN with the first cycle of CDE chemotherapy. For patients with similar risk of FN, the combined use of prophylactic antibiotics plus G-CSF can be considered, specifically in the first cycle of chemotherapy.

P-848 Prevention of chemotherapy-induced febrile neutropenia (FN) by the addition of granulocyte-colony stimulating factor (G-CSF) to antibiotics in small cell lung cancer (SCLC) patients at risk of FN: A prospective economic evaluation along a Dutch randomised phase III trial

P-848 Prevention of chemotherapy-induced febrile neutropenia (FN) by the addition of granulocyte-colony stimulating factor (G-CSF) to antibiotics in small cell lung cancer (SCLC) patients at risk of FN: A prospective economic evaluation along a Dutch randomised phase III trial

Prevention of chemotherapy-induced febrile neutropenia (FN) by antibiotics (AB) versus antibiotics plus granulocyte-colony stimulating factor (G-CSF) in small cell lung cancer (SCLC): A randomized phase III study

8002 Background: FN is a major complication of chemotherapy in patients (pts) with SCLC. G-CSF is used to prevent FN, but its primary use is only recommended in pts with a considerable (>40%) risk of FN (ASCO guidelines, JCO 2000). AB are also effective in preventing FN, even reduce infection-related mortality and are cost-effective (Tjan-Heijnen, Ann Oncol 2001). In this multicenter randomised phase III trial the role of combined primary prophylaxis with AB plus G-CSF in pts with SCLC at increased risk of FN was determined. Methods: Pts with SCLC-limited disease and performance status (PS) 2–3, or age over 60 years or judged not suitable for concurrent chemo/radiotherapy and pts with SCLC-extensive disease were considered at increased risk of FN. Pts were stratified for age (</≥ 60 years), PS (0–1/2), extend of disease (LD/ED) and line of therapy (1st/2nd) and randomised for primary prophylaxis with AB (ciprofloxacin 500mg + roxithromycin 150mg, bid, days 4–13) alone or in combination with G-CSF (filgrastim 5 μ g/kg/day days 4–13). Chemotherapy consisted of cyclophosphamide 1000mg/m2 day 1, doxorubicin 45mg/m2 day 1 and etoposide 100mg/m2 days 1,2,3, i.v., q 3 weeks, × 5. Primary endpoint: incidence of FN in first cycle, targeted accrual: N=156 pts (78/ arm). Results: See table;171 pts were eligible. Patient characteristics were well balanced. Conclusion: The addition of primary prophylactic G-CSF to prophylactic antibiotics significantly reduced the incidence of chemotherapy-related FN in SCLC patients at increased risk of FN, especially in the first cycle by 50%. Supported by a research grant of Dutch Healthcare Insurance Board. No significant financial relationships to disclose.

Prevention of chemotherapy-induced febrile neutropenia (FN) by antibiotics (AB) versus antibiotics plus granulocyte-colony stimulating factor (G-CSF) in small cell lung cancer (SCLC): A randomized phase III study

8002 Background: FN is a major complication of chemotherapy in patients (pts) with SCLC. G-CSF is used to prevent FN, but its primary use is only recommended in pts with a considerable (>40%) risk of FN (ASCO guidelines, JCO 2000). AB are also effective in preventing FN, even reduce infection-related mortality and are cost-effective (Tjan-Heijnen, Ann Oncol 2001). In this multicenter randomised phase III trial the role of combined primary prophylaxis with AB plus G-CSF in pts with SCLC at increased risk of FN was determined. Methods: Pts with SCLC-limited disease and performance status (PS) 2–3, or age over 60 years or judged not suitable for concurrent chemo/radiotherapy and pts with SCLC-extensive disease were considered at increased risk of FN. Pts were stratified for age (</≥ 60 years), PS (0–1/2), extend of disease (LD/ED) and line of therapy (1st/2nd) and randomised for primary prophylaxis with AB (ciprofloxacin 500mg + roxithromycin 150mg, bid, days 4–13) alone or in combination with G-CSF (filgrastim 5 μ g/kg/day days 4–13). Chemotherapy consisted of cyclophosphamide 1000mg/m2 day 1, doxorubicin 45mg/m2 day 1 and etoposide 100mg/m2 days 1,2,3, i.v., q 3 weeks, × 5. Primary endpoint: incidence of FN in first cycle, targeted accrual: N=156 pts (78/ arm). Results: See table;171 pts were eligible. Patient characteristics were well balanced. Conclusion: The addition of primary prophylactic G-CSF to prophylactic antibiotics significantly reduced the incidence of chemotherapy-related FN in SCLC patients at increased risk of FN, especially in the first cycle by 50%. Supported by a research grant of Dutch Healthcare Insurance Board. No significant financial relationships to disclose.