Neutropenia management and granulocyte colony-stimulating factor use in patients with solid tumours receiving myelotoxic chemotherapy—findings from clinical practice

Purpose

Clinical practice adherence to current guidelines that recommend primary prophylaxis (PP) with granulocyte colony-stimulating factors (G-CSFs) for patients at high (≥20 %) overall risk of febrile neutropenia (FN) was evaluated.

Methods

Adult patients with breast cancer, non-small cell lung cancer (NSCLC), small-cell lung cancer (SCLC), or ovarian cancer were enrolled if myelotoxic chemotherapy was planned, and they had an investigator-assessed overall FN risk ≥20 %. The primary outcome was FN incidence.

Results

In total, 1,347 patients were analysed (breast cancer, n?=?829; NSCLC, n?=?224; SCLC, n?=?137; ovarian cancer, n?=?157). Patients with breast cancer exhibited fewer individual FN risk factors than patients with other cancers and were far more likely to have received a high-FN-risk chemotherapy regimen. However, a substantial proportion of all patients (45–80 % across tumour types) did not receive G-CSF PP in alignment with investigator risk assessment and guideline recommendations. FN occurred in 127 patients overall (9 %, 95% confidence interval (CI) 8–11 %), and incidence was higher in SCLC (15 %) than other tumour types (8 % in ovarian and NSCLC, 9 % in breast cancer). A post hoc analysis of G-CSF use indicated that G-CSF prophylaxis was not given within the recommended timeframe after chemotherapy (within 1–3 days) or was not continued across all cycles in 39 % of patients.

Conclusions

FN risk assessment was predominantly based on clinical judgement and individual risk factors, and guidelines regarding G-CSF PP for patients at high FN risk were not consistently followed. Improved education of physicians may enable more fully informed neutropenia management in patients with solid tumours.     

Efficacy and safety of lipegfilgrastim compared with placebo in patients with non-small cell lung cancer receiving chemotherapy: post hoc analysis of elderly versus younger patients

Purpose

Lipegfilgrastim, a glycoPEGylated recombinant granulocyte colony-stimulating factor (G-CSF), reduces neutropenia duration and febrile neutropenia (FN) incidence in patients with cancer receiving myelosuppressive chemotherapy. A phase 3 trial of lipegfilgrastim was conducted in patients with advanced non-small cell lung cancer (NSCLC) receiving cisplatin/etoposide (which produces mild-to-moderate myelosuppression). Because patients aged >65 years are at higher risk for FN versus younger patients, this post hoc analysis compared outcomes in elderly (>65 years) versus younger participants in this trial.

Methods

Patients were randomized 2:1 to receive a once-per-cycle single subcutaneous injection of lipegfilgrastim 6 mg or placebo, with up to 4 cycles of every-3-week cisplatin (day 1) and etoposide (days 1–3). The primary end point was FN incidence during cycle 1. Outcomes were compared across treatment groups and by age groups (≤65 and >65 years).

Results

For patients aged ≤65 years, FN incidence during cycle 1 was similar in the lipegfilgrastim and placebo groups (3.0 vs 3.2 %, respectively), whereas for elderly patients, there was a reduction in FN incidence with lipegfilgrastim (0 vs 13.3 %, respectively). In both age subgroups, lipegfilgrastim showed a propensity to reduce the incidence and duration of severe neutropenia, time to absolute neutrophil count (ANC) recovery, and depth of ANC nadir. Adverse events were generally similar between groups.

Conclusions

This analysis suggests that in patients with a higher FN risk, such as the elderly patients of this study, lipegfilgrastim reduces not only the duration of severe neutropenia but also the incidence of FN.

     

Incidence of febrile neutropenia among early-stage breast cancer patients receiving anthracycline-based chemotherapy

Objectives

The aim of this study was to investigate the incidence of febrile neutropenia (FN) with adjuvant AC (doxorubicin and cyclophosphamide) chemotherapy among Asian early-stage breast cancer (ESBC) patients, to evaluate the impact of FN on chemotherapy delivery, and to identify specific risk factors that would predispose ESBC patients to FN.

Methods

This was a single-center, observational, retrospective cohort study conducted in Singapore. All ESBC patients who have received the AC regimen as adjuvant chemotherapy between January 2007 and July 2010 were included into the study. Patients did not receive granulocyte colony-stimulating factors (G-CSF) as primary prophylaxis.

Results

One hundred and eighty-nine patients and 729?cycles of chemotherapy were analyzed in this study, of which, majority were Chinese (84%). Median age of the patients was 54?years old (IQR 49–58). In total, 26 patients (13.8%) manifested at least one episode of FN, of which 17 patients developed FN during the first cycle of treatment. Patients who manifested FN received similar dose intensities of chemotherapy, compared to those patients who did not manifest FN (100% versus 98%, p?=?0.95). After adjusting for age, race, and presence of comorbidities, low body mass index (BMI) (<23?kg/m²) was found to be associated with a higher risk of FN (OR 4.4, 95% CI?=?1.65–12.01, p?=?0.003).

Conclusions

Asian patients are at moderate risk for FN when they receive the AC regimen for treatment of ESBC. Further studies should evaluate the role of G-CSF to reduce the occurrence of FN in Asian patients with low BMI.     

Efficacy and safety of early G-CSF administration in patients with head and neck cancer treated by docetaxel-cisplatin and 5-fluorouracil (DCF protocol): a retrospective study

Background

Induction chemotherapy with docetaxel-cisplatin and 5-fluorouracil (DCF) for locally advanced head and neck cancers (HNC) is associated with a high risk of severe neutropenia or febrile neutropenia (FN). We conducted a retrospective study to evaluate the efficacy and safety of administering granulocyte colony-stimulating factor (G-CSF) on day 3 (D3) during chemotherapy (early G-CSF stimulation) versus after the end of chemotherapy, as per current guidelines (i.e., after the end of 5-FU perfusion; D7), and its impact on patient outcomes.

Patients and methods

Patients ≥19 years old, with advanced HNC who received DCF induction chemotherapy (D and P 75 mg per meter squared (mg/m²) on day 1 and 5-FU 750 mg/m²/day from D1 to D5), were included in the analysis.

Results

Data of 70 patients were analyzed from 01 January 2003 to 01 December 2010. Mean age was 56 years (range 45 to 77 years). Thirty-six patients (51.4 %) received pegfilgrastim on D7, and 28 (40 %) started G-CSF prophylaxis during chemotherapy; 12 (17.1 %) had daily filgrastim and 16 (22.9 %) pegfilgrastim on D3. Overall response rate (ORR) was 89.6 % (three early deaths due to infectious complications; 4.3 %). The 3-year overall survival (OS) rate was 72.8 %. FN rate was 14.3 % and chemotherapy delay was 12.9 %. In the D7 G-CSF arm, incidence of grade 3–4 neutropenia (p?=?0.023), FN (p?=?0.029), and cycle delays (p?=?0.006) was statistically higher than the “early” G-CSF arm. A decrease of OS was observed at 2 years (from 85.1 to 63.5 %) of chemotherapy discontinuation or FN (p?=?0.0348).

Discussion

Early administration of G-CSF is safe and seems to be more effective than D7. Future prospective trials are required to confirm our results.     

Feasibility and safety of a reduced duration of therapy of colony-stimulating factor in a dose-dense regimen

Purpose

The risk of febrile neutropenia (FN) in cancer patients receiving chemotherapy is mainly due to the type of chemotherapy regimen and the presence of specific risk factors in patients. The recent trend of using a dose-dense treatment schedule has enhanced the risk of FN. In the present prospective study, we evaluated the feasibility of a reduction of duration of therapy with colony-stimulating factor (G-CSF) in a dose-dense regimen.

Methods

Between June 2002 and December 2011, 107 patients with a new diagnosis of non-Hodgkin lymphoma (NHL) receiving dose-dense chemotherapy, every 14 days, were included in the study. The primary endpoint was defined as the completion of planned chemotherapy cycles as scheduled. Secondary endpoints were median number of administered G-CSF doses (vials), incidence of FN, hospitalization and toxicity.

Results

The planned chemotherapy cycles (primary endpoint) were completed by 84.1 % of patients. The median number of G-CSF (lenograstim) doses administered for each patient was 24 (range 10–35), which corresponds to a median of five vials (range 0–10) for each cycle. Grades 3–4 toxicities, related to G-CSF administration, included neutropenia and thrombocytopenia (14.0 and 1.9 %, respectively). No grades 3–4 bone pain was detected. The incidence of FN and hospitalization was 9.3 % (10/107) and 4.5 % (5/107), respectively.

Conclusions

Reduced dosage of G-CSF allows dose-dense chemotherapy scheduling, limits exposure to G-CSF and also represents an opportunity for cost savings.     

Breakthrough febrile neutropenia and associated complications among elderly cancer patients receiving myelosuppressive chemotherapy for solid tumors and lymphomas

Objective

This study evaluated the prevalence, impact and predictive factors for the occurrence of febrile neutropenia (FN) in elderly patients receiving adjuvant myelosuppressive chemotherapy despite primary prophylaxis with G-CSF (breakthrough FN).

Methods

This was a single-centre, observational, retrospective cohort study. Elderly cancer patients (≥65 years old) who have received adjuvant chemotherapy with primary prophylaxis using G-CSF from Jan 2008 to Aug 2011 were included. Variables identified by the univariate analysis as being associated with FN were included in a multivariable logistic model to investigate the independence of its association with FN.

Results

One hundred and forty-five patients and 704 cycles of chemotherapy were analyzed in this study, of which majority were Chinese (79.3 %). The median age of the patients was 69 years old (IQR: 66, 74). Majority of these patients were diagnosed with lymphoma (54.5 %), followed by breast cancer (34.5 %) and small cell lung cancer (8.3 %). In total, 24 patients (16.6 %) manifested at least one episode of FN, of which 41.7 % occurred during the first cycle of treatment. Only a minority of FN patients had clinically significant dose delay or reduction (25.0 % and 12.5 %, respectively). After adjustment with confounders (gender, baseline lymphocyte counts and baseline absolute neutrophil counts), patients with ≥2 comorbidities were at higher risk to develop breakthrough FN (AOR?=?4.42, 95 %CI: 1.36–14.40, p?=?0.014).

Conclusion

Breakthrough FN is prevalent among elderly cancer patients receiving adjuvant chemotherapy despite G-CSF support, particularly among patients with more than two comorbidities.     

Use of pegfilgrastim primary prophylaxis and risk of infection,by chemotherapy cycle and regimen,among patients with breast cancer or non-Hodgkin’s lymphoma

Purpose

This study aims to examine granulocyte colony-stimulating factor (G-CSF) prophylaxis by cancer type, chemotherapy regimen, and cycle in a real-world setting to assess if practice conforms to clinical guidelines, which recommend G-CSF prophylaxis every cycle when a patient’s risk of febrile neutropenia (FN) is 20 % or greater, and to describe the incidence of FN among patients who discontinue pegfilgrastim (peg) prophylaxis.

Methods

The cohort was selected from administrative claims data and includes adults diagnosed with non-Hodgkin’s lymphoma (NHL) or breast cancer (BC) who began chemotherapy 2005–2010.

Results

About 83.2 % of the 4,470 patients with BC treated with dose-dense doxorubicin, cyclophosphamide (ddAC), 83.6 % of 2,197 patients with BC treated with docetaxel, doxorubicin, cyclophosphamide (TAC), and about 55.6 % of the 2,722 patients with NHL treated with cyclophosphamide, doxorubicin, vincristine, with or without prednisone for 3-week cycles (CHOP-R Q3W) received peg prophylaxis in cycle 1. Among patients on these regimens who received peg prophylaxis in cycle 1 and were still on the regimen in cycle 4, about 90 % received peg prophylaxis in that cycle. Among patients with BC or NHL who discontinued G-CSF, the incidence proportion of infection or FN varied by regimen and cycle, with a range from 0 to 14 %.

Conclusions

Despite clinical guidelines recommending G-CSF prophylaxis with chemotherapy regimens with a high risk of FN, many NHL and BC patients do not receive FN prophylaxis in cycle 1. However, among patients who receive G-CSF in cycle 1 and remain on the regimen, the majority appear to continue prophylaxis as indicated.     

Full-dose chemotherapy in early stage breast cancer regardless of absolute neutrophil count and without G-CSF does not increase chemotherapy-induced febrile neutropenia

Purpose

Does giving full-dose adjuvant chemotherapy to patients with early stage breast cancer (ESBC) regardless of the day-before absolute neutrophil count (ANC) lead to an increased incidence of chemotherapy-induced febrile neutropenia (CIFN)? What factors may predispose patients to CIFN?

Methods

This was a retrospective chart review conducted on all patients receiving adjuvant chemotherapy for ESBC at a mid-sized community hospital in Toronto, Ontario, Canada between September 2005 and August 2011. Day-before CBC data were collected along with other patient characteristics. CIFN was confirmed by hospital records. One hundred fifty-four patients met the inclusion criteria. Overall, 830 cycles of chemotherapy were analyzed. Univariate and multivariate logistic regression analyses were used to identify risk factors for CIFN.

Results

Twenty-two episodes of CIFN were observed. There was no significant difference in day-before ANC between patients who developed CIFN relative to those who did not. The day-before ANC was <1.5?×?10⁹/L for 88 cycles of chemotherapy. ANC analyzed as a continuous variable showed that the odds ratio (OR) for CIFN was 0.97 (95 % CI 0.82–1.13, p?=?NS). The pseudo R ² statistic, which is a measure of variability accounted for by a regression model, was only 0.0008, indicating that ANC explained less than 1 % of the variability in the risk of CIFN. The most significant predictor of CIFN was the chemotherapy regimen, with docetaxel (Taxotere)/cyclophosphamide demonstrating the highest risk (OR 7.1, 95 % CI 1.4–34.9, p?=?0.016).

Conclusions

Full-dose adjuvant chemotherapy may be given to patients with ESBC regardless of the day-before ANC, without significantly increasing the risk of CIFN. The chemotherapy regimen is the most significant predictor for CIFN.     

Reducing febrile neutropenia rates in early breast cancer. Experience of two UK cancer centres

Purpose

Primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) is used in many institutions across the UK due to unacceptable febrile neutropenia (FN) rates with FEC-D (fluorouracil, epirubicin, cyclophosphamide–docetaxel). The resultant reduction in FN rate is thought to maintain dose intensity and improve patient experience. This retrospective study was performed to assess whether the addition of G-CSF primary prophylaxis into daily clinical practice has achieved these aims.

Methods

Collaborative audit performed in two UK cancer centres before and after the integration of G-CSF primary prophylaxis with FEC-D. The primary objective was FN rate.

Results

Data from 342 patients were analysed, 151 before routine use of primary G-CSF and 191 after. The FN rates were 30 and 11 %, respectively. Despite the 99 % adherence to primary G-CSF policy, there were more dose reductions (8 increased to 13 %) and dose delays (11 increased to 23 %) following the use of G-CSF primary prophylaxis. This appeared to be due to non-FN toxicities. Inpatient days decreased substantially from 93 to 16 and antibiotic courses from 28 to 13 (per hundred patients).

Conclusions

Near universal adherence to the G-CSF policy in FEC-D treatment has led to a reduction in FN rate and inpatient days but has not translated into improved dose intensity. This collaborative audit allows sufficient data to give insight into current practice and generate hypotheses for further investigation.     

Granulocyte colony-stimulating factor (G-CSF) patterns of use in cancer patients receiving myelosuppressive chemotherapy

Purpose

Febrile neutropenia (FN) is a common and serious complication of myelosuppressive chemotherapy. Guidelines recommend primary granulocyte colony-stimulating factors (G-CSF) prophylaxis (PPG) in patients with a high risk (HR, >20 %) of developing FN. We performed a retrospective analysis using a subset of the Medicare 5 % database to assess patterns of G-CSF use and FN occurrence among elderly cancer patients receiving myelosuppressive chemotherapy.

Methods

Chemotherapy courses for patients aged 65+?years were identified; only the first course was used for this analysis. Using clinical guidelines, chemotherapy regimens were classified as HR or intermediate risk (IR) for FN. The first administration of G-CSF was classified as either PPG (within the first 5 days of the first cycle), secondary prophylaxis, or reactive.

Results

Twelve thousand seven hundred seven courses across five tumor types were classified as having a HR or IR regimen. G-CSF was used in 24.5–73.8 % of patients receiving a HR FN regimen, with the highest use in breast cancer or NHL. Except for breast cancer (where PPG was used in 52.1 %), PPG was given in less than half of patients receiving a HR regimen. Depending on the tumor type, 4.8–22.6 % of patients with a HR regimen had a neutropenia-related hospitalization.

Conclusions

Guidelines recommend PPG with HR FN regimens and older age (>65 years), an important risk factor for developing severe neutropenic complications. However, our results show that in this elderly population, PPG was not routinely used (range 4.8–52.1 %) in patients receiving HR FN regimens. Careful attention to FN risk factors, including chemotherapy regimen and patient age, is needed when planning treatment strategies.     

Pharmacoeconomics of Granulocyte Colony-Stimulating Factor: A Critical Review

Introduction

In the USA, neutropenia-related hospitalization is estimated to occur in 34.2 cases per 1,000 chemotherapy-treated patients. The cost of hospitalization is significant with estimates ranging, on average, from $10,000 to $30,000 per neutropenia-related hospitalization. Prophylactic use of granulocyte colony-stimulating factor (G-CSF) significantly reduces the risk and duration of neutropenia-related negative events. However, the exact economic benefits of using G-CSF prophylactically are not completely known. The objective of this review is to examine the cost of G-CSF as primary prophylaxis (PP) as well as when used reactively to treat severe neutropenia (SN) or febrile neutropenia (FN).

Methods

Electronic databases were searched for studies published up to January 2014.

Results

The evidence supporting the cost-effectiveness of PP use of G-CSF is inconsistent. The cost savings of PP use of G-CSF associated with the reduction of neutropenia-related events are offset by the increased costs associated with improved chemotherapy administration. Cost savings due to the reduction in mortality and disease/symptoms and use of dose-dense regimens have not been adequately incorporated into previous cost-effectiveness studies. Available data suggest that using G-CSF in conjunction with antibiotics is more cost-effective than antibiotics alone when treating patients with SN/FN. Recent studies of biosimilars suggest that they are as effective as originator G-CSFs and, given their lower cost, could represent a cost-effective alternative. Finally, studies have not taken into consideration the indirect patient costs of experiencing a neutropenia-related event.

Conclusion

G-CSF use is effective in preventing SN/FN. Costs due to hospitalization and other neutropenia-related events are lower in patients treated with G-CSF as PP versus untreated patients. Despite this, many studies have not found solid evidence for the overall cost-effectiveness of PP use of G-CSF. One possibility for this is that patients receiving G-CSF prophylactically often receive more intense chemotherapy regimens, have better relative dose intensity, and fewer dose delays, and thereby have greater costs associated with chemotherapy administration than patients who do not receive G-CSF.     

Direct costs associated with febrile neutropenia in inpatients with hematological diseases in Singapore

Purpose

This prospective cohort study aims to investigate the direct hospitalization costs incurred during febrile neutropenia (FN) in inpatients with underlying hematological conditions and also to elucidate the factors associated with a high cost of managing febrile neutropenia.

Methods

Patients with underlying hematological conditions and documented FN were recruited between October 2008 and February 2011. FN-related costs included all costs incurred from the first day of FN until the last day of antibiotics prescribed. Relevant clinical factors were analyzed using generalized estimating equation models to elucidate the factors that were associated with higher costs of FN.

Results

A total of 175 patients were recruited with 303 documented episodes of FN. In non-transplant patients, 75.6 % of the FN episodes occurred. The median and mean cost incurred for each FN episode was USD9,060 (interquartile range?=?USD5,047–16,631) and USD15,298 (standard deviation?±?USD17,459), respectively, accounting for approximately 38 % of the median total hospitalization cost and 37 % of the mean total hospitalization cost. The ward charges (44.1 %) constituted the largest component of the cost, followed by the laboratory charges (27.3 %) and medications (18.7 %), of which antimicrobials constituted 9.6 % of the cost of FN. The factors associated with higher costs of FN include cytomegalovirus reactivation (p?<?0.001), longer duration of antibiotics (p?<?0.001), lower absolute neutrophil count nadir (p?<?0.001), allogeneic stem cell transplantation (p?<?0.01), and diagnosis of invasive fungal infection (p?<?0.05).

Conclusion

The economic cost of management of FN in hematology inpatients is considerable and in addition to the overall risk of mortality for this condition. Strategies to reduce FN or ameliorate its costs are essential for this group of patients.     

Periodontal status and bacteremia with oral viridans streptococci and coagulase negative staphylococci in allogeneic hematopoietic stem cell transplantation recipients: a prospective observational study

Aim

This study was aimed to investigate whether any association could be found between the presence of an inflamed and infected periodontium (e.g., gingivitis and periodontitis) and the development of bacteremia during neutropenia following allogeneic hematopoietic stem cell transplantation (HSCT).

Methods

Eighteen patients underwent a periodontal examination before HSCT. Patients were classified as periodontally healthy [all periodontal pocket depths (PPD)?≤?4 mm and bleeding on probing (BOP)?≤?10 %) or as having gingivitis/periodontitis (PPD?≥?4 mm and BOP?>?10 %]. Oral mucositis (OM) was scored using the daily mucositis score. Blood cultures were taken at least twice weekly.

Results

Five patients were periodontally healthy, while 13 patients had gingivitis or periodontitis. Twelve patients (67 %) developed bacteremia during neutropenia, of which 11 patients (61 %) had one or more episodes of bacteremia due to coagulase-negative staphylococci (CONS, most often Staphylococcus epidermidis) or to oral viridans streptococci (OVS), or both. Patients with gingivitis/periodontitis more often had bacteremia than those with a healthy periodontium (p?=?0.047), and BOP was associated with bacteremia (p?=?0.049). All patients developed ulcerative OM, but its severity and duration were not associated with bacteremia. OM duration and the length of stay in the hospital were strongly correlated (R?=?0.835, p?≤?0.001).

Conclusion

This study indicates that periodontal infections may contribute to the risk of developing OVS and CONS bacteremia during neutropenia following HSCT. While our results point to the importance of periodontal evaluation and management before HSCT, further studies on periodontal contribution to systemic infectious complications are warranted.     

Incidence of febrile neutropenia in early stage breast cancer patients receiving adjuvant FEC-D treatment

Purpose

The purpose of this study is to determine the incidence of febrile neutropenia (FN) among women receiving FEC-D (flurouracil 500 mg/m², epirubicin 100 mg/m², and cyclophosphamide 500 mg/m² every 3 weeks for three cycles followed by docetaxel 100 mg/m² every 3 weeks for three cycles) chemotherapy for early stage breast cancer (ESBC) and the impact of primary granulocyte colony-stimulating factor (G-CSF) prophylaxis in a non-clinical trial setting.

Patients and methods

A retrospective chart review of women referred for ESBC to The Moncton Hospital between 2005 and 2010 evaluated patient and disease characteristics, adjuvant chemotherapy receipt, G-CSF usage, FN incidence, hospital admission rates, and length of stay. Association of variables with FN was examined, and exploratory multivariable logistic regression modeling examined the impact of baseline variables on risk of FN.

Results

Of 520 patients enrolled in the database, 251 (48.3 %) received adjuvant chemotherapy for ESBC. Most (66.9 %) received FEC-D. Overall, 55 (21.9 %) patients developed FN. Forty-four (26.2 %) patients on FEC-D developed FN. Forty of 129 (31.0 %) FEC-D patients who did not receive primary G-CSF prophylaxis developed FN, versus 4 of 39 (10.3 %) receiving G-CSF. Receipt of FEC-D or TC (docetaxel 75 mg/m² and cyclophosphamide 600 mg/m² every 3 weeks for four or six cycles) was associated with odds ratios of 6.5 or 6.77, respectively, for the development of FN. Receipt of trastuzumab with chemotherapy was associated with an odds ratio of 3.48 for developing FN versus no trastuzumab. Primary G-CSF prophylaxis led to a 63 % reduction in the odds ratio of developing FN.

Conclusions

Incidence of FN with FEC-D treatment is considerably higher in clinical practice than reported in phase III trials. Consistent with ASCO guidelines, prophylactic G-CSF should be considered for all ESBC patients receiving adjuvant FEC-D.     

Bacteria causing bacteremia in pediatric cancer patients presenting with febrile neutropenia—species distribution and susceptibility patterns

Purpose

Infections are a major cause of morbidity and mortality in pediatric cancer patients. The aim of this study was to establish the microbiological spectrum and the susceptibility patterns of bacteremia-causing bacteria in pediatric cancer patients with febrile neutropenia in relation to the use of prophylactic and empirical antibiotics.

Methods

We analyzed positive blood cultures of pediatric cancer patients presenting with febrile neutropenia between 2004 and 2011 in Groningen and Amsterdam (the Netherlands) and in Bern (Switzerland), using different antibiotic prophylactic and empirical regimens.

Results

A total of 156 patients with 202 bacteremias, due to 248 bacteria species, were enrolled. The majority (73 %) of bacteremias were caused by Gram-positive bacteria. Gram-negative bacteria, especially Pseudomonas aeruginosa, were observed significantly more often in Bern, where no fluoroquinolone prophylaxis was used. Ciprofloxacin-resistant bacteria were cultured more often from patients who did receive ciprofloxacin prophylaxis, compared to the patients who did not (57 versus 11 %, p?=?0.044).

Conclusions

Gram-positive bacteria predominated in this study. We showed that the use of prophylactic antibiotics in pediatric cancer patients was associated with increased resistance rates, which needs further study. The strategy for empiric antimicrobial therapy for febrile neutropenia should be adapted to local antibiotic resistance patterns.     

Comparison of pegfilgrastim on day?2 vs. day?4 as primary prophylaxis of intense dose-dense chemotherapy in patients with node-positive primary breast cancer within the prospective, multi-center GAIN study: (GBG 33)

Background

Preliminary data suggest that pegfilgrastim given on day?4 (P4) might be superior to pegfilgrastim on day?2 (P2) in reducing grade 4 leucopenia.

Methods

Patients with node-positive primary breast cancer receiving epirubicin?Cpaclitaxel?Ccyclophosphamide chemotherapy were randomized to receive P2 versus P4. Primary endpoint was leucopenia grade 4, assuming a risk reduction of 50% with P4 from 50% in P2 to 25% with P4.

Results

Three-hundred fifty-one patients were randomized to P2 (n?=?174) versus P4 (n?=?177). The rate of leucopenia (grade 4) was 47.1% with P2 and 42.0% with P4 (p?=?0.387), neutropenia (grade 3?+?4) was 47.9% versus 40.8% (p?=?0.337), FN was 4.7% versus 8.0% (p?=?0.271), and infections was 29.9% versus 25.4% (p?=?0.404), respectively.

Conclusion

This study failed to demonstrate that pegfilgrastim on day?4 was more efficacious than on day?2 with respect to grade 4 leucopenia (the primary endpoint), febrile neutropenia, or infections.     

Incidence of bone pain in patients with breast cancer treated with lipegfilgrastim or pegfilgrastim: an integrated analysis from phase II and III studies

Purpose

Lipegfilgrastim is a once-per-cycle, fixed-dose, glycoPEGylated recombinant granulocyte colony-stimulating factor (G-CSF) recently approved in Europe to reduce the duration of chemotherapy-induced neutropenia and incidence of febrile neutropenia in patients with cancer receiving chemotherapy. Bone pain-related (BPR) adverse events are commonly associated with G-CSF therapy. This post hoc analysis examined BPR treatment-emergent adverse events (TEAEs) in two comparative studies of lipegfilgrastim or pegfilgrastim in patients receiving chemotherapy.

Methods

A post hoc analysis was conducted using integrated data from two double-blind randomized studies in patients with breast cancer receiving docetaxel and doxorubicin and treated prophylactically with subcutaneous lipegfilgrastim 6 mg or pegfilgrastim 6 mg once per cycle. BPR TEAEs were defined as arthralgia, back pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort, musculoskeletal pain, myalgia, neck pain, noncardiac chest pain, and pain in extremity. Relationship of BPR TEAEs to study treatment or chemotherapy was also reported by the investigators.

Results

The analysis included 306 patients (lipegfilgrastim: n?=?151; pegfilgrastim: n?=?155). The proportion of patients experiencing BPR TEAEs was similar with lipegfilgrastim and pegfilgrastim (25.2 vs 21.9 %, respectively), as was the proportion of patients experiencing BPR treatment-emergent adverse drug reactions (TEADRs) (18.5 vs 16.8 %, respectively). No BPR TEADRs were serious, and none led to discontinuation.

Conclusions

Nonsevere BPR TEAEs and TEADRs were observed in patients with breast cancer receiving chemotherapy and G-CSF; rates of BPR events were similar between lipegfilgrastim and pegfilgrastim. The similar BPR safety profile of lipegfilgrastim and pegfilgrastim provides support for use in patients with breast cancer receiving chemotherapy.

     

Severe neutropenia and relative dose intensity among patients <65 and ≥65 years with non-Hodgkin’s lymphoma receiving CHOP-based chemotherapy

Purpose

The objective of this study was to describe the incidence of grade 3/4 neutropenia, patterns of chemotherapy treatment, and granulocyte colony-stimulating factor (G-CSF) use patterns among patients with non-Hodgkin’s lymphoma (NHL) <65 and ≥65 years.

Methods

This retrospective, observational study included adult patients with NHL who received cyclophosphamide, doxorubicin, vincristine, and prednisone?±?rituximab (CHOP?±?R) from January 2006 to June 2010.

Results

A total of 1,579 patients were included, with 54.1 % <65 years and 45.9 % ≥65 years. Most received CHOP-R on a Q3W schedule. Among patients <65 years, the incidence of grade 3/4 neutropenia was 52.3 %, the mean relative dose intensity (RDI) was 80.4 %, and the incidences of dose delays and reductions were 26.5 and 9.6 %, respectively. Among patients ≥65 years, the incidence of grade 3/4 neutropenia was 63.2 %, the mean RDI was 73.9 %, and the incidences of dose delays and reductions were 24.6 and 24.9 %, respectively. Most patients (86.9 %) received G-CSF. Among patients <65 years, 71.9, 17.4, and 10.7 % first received G-CSF as primary prophylaxis, secondary prophylaxis, or treatment, respectively. Among patients ≥65 years, 80.1, 11.6, and 8.3 % first received G-CSF as primary prophylaxis, secondary prophylaxis, or treatment, respectively.

Conclusions

Chemotherapy regimens and schedules were similar among age groups. Grade 3/4 neutropenia, reduced RDI, and dose delays were common in both age groups, though patients ≥65 years had a higher incidence of dose reductions. In spite of these similarities, patients <65 years were less likely to receive primary prophylactic G-CSF. Thus, careful assessment of neutropenia risk factors is needed across age groups to determine appropriate G-CSF use and support planned chemotherapy.     

Primary prophylaxis with granulocyte colony-stimulating factor (GCSF) reduces the incidence of febrile neutropenia in patients with non-Hodgkin lymphoma (NHL) receiving CHOP chemotherapy treatment without adversely affecting their quality of life: cost–benefit and quality of life analysis

Purpose

Treatment of non-Hodgkin lymphoma (NHL) with cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP) is known to be associated with a significant risk of febrile neutropenia (FN) of up to 50 % [Osby et al. 2003 Blood 101(10): 3840–3848; Lyman and Delgado 2003 Cancer 98(11): 2402–2409]. This study sought to examine the impact of primary granulocyte colony-stimulating factor (GCSF) prophylaxis on the incidence of FN, quality of life and overall cost.

Methods

In this retrospective cohort study, a group of 65 consecutive patients who received CHOP chemotherapy for NHL between December 2006 and October 2009 was studied. Patients either received filgrastim (300 mcg, average of seven doses), pegylated filgrastim (6 mg, single dose), or no GCSF prophylaxis. In addition, 19 patients were asked to complete Functional Assessment of Cancer Therapy: General quality-of-life questionnaires.

Results

Overall, patients who received primary GCSF prophylaxis had significantly fewer FN compared to those who did not (5 vs. 60 %, p?<?0.0001; numbers needed to treat of 1.8; 95 % confidence interval, 1.6–2.9). Cost–benefit analysis showed that the GCSF prophylaxis was associated with only a small increase in direct financial cost ($238 NZD [US$189] more to give primary GCSF prophylaxis per patient vs. no prophylaxis). The quality of life assessment showed that the patients’ quality of life scores were similar to the published data from the validation study population (466 patients with mixed cancers) for Functional Assessment of Cancer Therapy.

Conclusions

Our study shows that primary GCSF prophylaxis is effective in preventing FN in patients receiving CHOP chemotherapy for NHL without adversely affecting their quality of life, and is cost effective.     

Characteristics of unplanned hospital admissions due to drug-related problems in cancer patients

Background

Studies have examined drug-related problems (DRPs) that have led to hospital admissions in the general population. However, there is a lack of information on the characteristics of DRPs in the cancer population.

Objective

The objective of this study was to investigate the type, causality, severity, and preventability of DRPs that result in unplanned hospitalizations among cancer patients.

Methods

This was a prospective, cohort study conducted in two oncology wards between July and December 2012. All patients who were diagnosed with solid tumor or lymphoma and required unplanned hospitalization were included. The incidence of DRPs among hospital admissions was captured, and the nature of the DRPs (causality, severity, and preventability) was characterized.

Results

There were 1,299 admissions and 1,275 were eligible for analysis. Among the 1,275 eligible admissions, 158 (12.4 %) were considered to be associated with a DRP. In the 158 admissions associated with DRPs, 164 DRPs were found. The majority of the DRP-related admissions were adverse drug reactions (ADRs) (n?=?155/164, 94.5 %), probable (n?=?98, 59.8 %), moderately severe (n?=?155, 94.5 %), and probably or definitely preventable (n?=?86, 52.4 %). Most patients with DRPs recovered and were discharged. Febrile neutropenia was the most common adverse drug reaction, and drug combinations involving antihypertensives and long-term corticosteroids raised the risks for potential drug-drug interactions among patients with cancer.

Conclusion

The incidence of DRP-induced unplanned hospital admissions was 12.4 % among cancer patients. Approximately half of these were preventable events.