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.     

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.     

Clinical efficacy of adjunctive G-CSF on solid tumor and lymphoma patients with established febrile neutropenia

Background

The use of granulocyte colony-stimulating factor (G-CSF) as a prophylaxis against febrile neutropenia (FN) is well documented in the literature; however, the therapeutic use of G-CSF in the treatment of FN remains controversial. This study assessed the efficacy of adjunctive G-CSF in the treatment of FN by evaluating clinical outcomes.

Methods

This was a single-center, prospective cohort study conducted at the National Cancer Center in Singapore. Adult patients who had received chemotherapy and developed FN between January 2009 and January 2012 were included in the analysis. The clinical efficacy of adjunctive G-CSF was evaluated by investigating the duration of hospitalization, duration to absolute neutrophil count (ANC) recovery, duration of grade IV neutropenia, duration to fever resolution, duration of antibiotic therapy, and incidence of documented infections. A multivariate analysis was performed to identify patients who could potentially benefit from adjunctive G-CSF.

Results

Four hundred and thirty patients were analyzed. Majority manifested low-risk FN (81.2 %) based on the Multinational Association of Supportive Care in Cancer (MASCC) scoring. Compared to patients who did not receive adjunctive G-CSF, patients receiving adjunctive G-CSF had a nonsignificant reduction in the duration of hospitalization (3.5 vs. 3.7 days, p?=?0.41) and in ANC recovery time (3.4 vs. 3.5 days, p?=?0.76). Neutropenia-related mortality was lower among those who have received adjunctive G-CSF (2.4 vs. 8.4 %, p?=?0.006). Patients of Indian ethnicity and those who underwent gemcitabine-containing chemotherapy were less likely to receive adjunctive G-CSF treatment.

Conclusions

This observational study suggested that adjunctive G-CSF may confer clinical benefits among solid tumor and lymphoma patients with established febrile neutropenia. Further research should be conducted to validate the findings.     

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.     

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.     

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.     

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.     

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.     

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.     

Exploring clinical determinants and anxiety symptom domains among Asian breast cancer patients

Purpose

Psychological distress, such as anxiety, is commonly experienced by breast cancer patients. This study was designed to evaluate the presentation of anxiety symptom domains among Asian breast cancer patients and to identify clinical factors that were associated with occurrence of anxiety.

Methods

An observational study was conducted between August 2009 and January 2012. Breast cancer patients (stages I to III) with different chemotherapy treatment status completed the Beck Anxiety Inventory (BAI) to evaluate the prevalence and severity of their anxiety symptoms. Demographical and clinical data were collected. Multiple linear regression was conducted to delineate clinical factors associated with anxiety.

Results

A total of 319 patients were recruited (age: 51?±?9 years; 80.9 % Chinese; 69.6 % stage I/II). The median BAI total score was 8 (IQR, 4–14). Anxiety severities varied greatly across patients with different chemotherapy treatment status: patients who were receiving concurrent chemotherapy at the point of assessment (n?=?161) experienced more severe anxiety symptoms, as compared to pre-chemotherapy receiving (n?=?78) patients and post-chemotherapy (n?=?88) patients (29.8 % vs. 9.0 % vs. 20 %, respectively; p?=?0.021). Regression model identified fatigue (p?<?0.001) and the concurrent receipt of chemotherapy (p?<?0.001) as the strongest factors associated with anxiety. Concomitant neuropsychiatric medicines (antidepressants, anxiolytics, and hypnotics) were moderately associated with anxiety occurrence.

Conclusions

This is the largest series to date to evaluate anxiety symptom domains among Asian breast cancer patients. Results suggest that toxicities of chemotherapy may have contributed to the presentation of anxiety symptoms.     

Palonosetron in combination with 1-day versus 3-day dexamethasone for prevention of nausea and vomiting following moderately emetogenic chemotherapy: a randomized, multicenter, phase III trial

Purpose

A phase III trial assessed the efficacy of palonosetron plus dexamethasone given once in preventing acute and delayed chemotherapy-induced nausea and vomiting (CINV) following a broad range of moderately emetogenic chemotherapy (MEC) regimens.

Methods

This multicentre, randomized, open-label, non-inferiority trial evaluated two different treatment groups. One group received palonosetron (0.25?mg intravenously) and dexamethasone (8?mg intravenously) before chemotherapy, while the other was administered the same regimen on day?1 followed by dexamethasone 8?mg orally on days?2 and 3. The primary endpoint was complete response (CR; defined as no emetic episodes and no rescue medication) during the overall phase (days?1?C5 after chemotherapy initiation). The non-inferiority margin was predefined as a 15% difference between groups in the primary endpoint.

Results

Of 332 chemotherapy-na?ve patients included in the intention-to-treat analysis, 65.1% were female, and 35.2% received anthracycline plus cyclophosphamide (AC)-based regimens. Overall CR rates were 67.5% for those administered dexamethasone only on day?1 (n?=?166), and 71.1% for those also administered dexamethasone on days?2 and 3 (n?=?166; difference ?3.6% (95% confidence interval, ?13.5 to 6.3)). CR rates were not significantly different between groups during the acute (0?C24?h post-chemotherapy; 88.6% versus 84.3%; P?=?0.262) and delayed phases (days?2?C5; 68.7% versus 77.7%; P?=?0.116).

Conclusions

Palonosetron plus single-dose dexamethasone administered before common MEC regimens provide protection against acute and delayed CINV which is non-inferior to that of palonosetron plus dexamethasone for 3?days. However, the major benefit of the single-day regimen occurs in patients receiving non-AC MEC regimens.     

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.     

Palonosetron plus single-dose dexamethasone for the prevention of nausea and vomiting in women receiving anthracycline/cyclophosphamide-containing chemotherapy: meta-analysis of individual patient data examining the effect of age on outcome in two phase III trials

Purpose

Data from two randomized trials, evaluating a single-day regimen of palonosetron plus dexamethasone against emesis due to moderately emetogenic chemotherapy, were assessed for the impact of age on outcome in a pooled sample of women receiving anthracycline and/or cyclophosphamide (AC)-containing chemotherapy.

Methods

Chemo-naïve breast cancer patients randomized to receive palonosetron (0.25 mg) plus dexamethasone (8 mg IV) on day 1 of chemotherapy (n?=?200), or the same regimen followed by oral dexamethasone (8 mg) on days 2 and 3 (n?=?205), were included in the analysis. The primary endpoint was complete response (CR: no vomiting and no rescue anti-emetics) in the 5-day study period. The effect of the 1-day regimen and age (<50 and ≥50 years) was investigated by a meta-analysis of individual patient data.

Results

Younger patients comprised 43 % and 49 % of the 1-day and 3-day regimen groups, respectively; 94 % of the pooled sample received the AC combination. There were no between-treatment differences in CR rate according to age during all observation periods. In the 1-day regimen group, 55.2 % of younger patients achieved overall CR compared with 54 % of older patients. In the 3-day regimen group, 51.5 % of younger patients achieved overall CR compared with 58.7 % of older patients. In the adjusted analysis, younger age was not associated with overall CR to treatment (risk difference, ?3.1 %; 95 % CI, ?13.0 to 6.7 %; P?=?0.533).

Conclusions

These results provide evidence that, irrespective of age, the dexamethasone-sparing regimen is not associated with a significant loss in overall anti-emetic protection in women undergoing AC-containing chemotherapy.     

Efficacy and safety of intravenous voriconazole and intravenous itraconazole for antifungal prophylaxis in patients with acute myelogenous leukemia or high-risk myelodysplastic syndrome

Purpose

To compare the efficacy and safety of voriconazole with itraconazole as prophylaxis in leukemia patients.

Methods

Open-label, randomized study. Patients with acute myelogenous leukemia or high-risk myelodysplastic syndrome undergoing induction chemotherapy or first salvage were eligible. Patients received voriconazole (400?mg intravenous (IV) every 12?h for two doses, followed by 300?mg BID) or itraconazole (200?mg IV twice daily for 2?days, followed by 200?mg IV daily).

Results

A total of 127 patients were enrolled. Four were excluded because they did not receive study drug (n?=?3) or received two antifungal agents during the first week on study (n?=?1), leaving 123 patients for analysis. None of the 71 patients receiving voriconazole developed proven or probable invasive fungal infection, compared to two (4%) of the 52 patients receiving itraconazole (P?=?0.17). Drug discontinuation because of adverse events occurred in 15 patients (21%) receiving voriconazole and six (11%) receiving itraconazole (P?=?0.23).

Conclusions

Voriconazole is a good alternative for prophylaxis in patients with leukemia. Elevated baseline bilirubin levels were associated with a higher risk of side effects in patients receiving IV voriconazole or IV itraconazole. Monitoring of liver function and drug levels should be considered for some patients.     

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.     

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.     

The impact of chemotherapy-related nausea on patients' nutritional status, psychological distress and quality of life

Purpose

Nausea is a troublesome and distressing symptom for patients receiving chemotherapy. While vomiting is well controlled with current antiemetics, nausea is a more difficult symptom to manage. The aim of this study was to assess the impact of nausea on nutritional status, quality of life and psychological distress.

Methods

This was a prospective observational study over two cycles of chemotherapy. Patients completed the Multinational Association of Supportive Care in Cancer Antiemesis Tool, a measure of nutritional status (Patient-Generated Subjective Global Assessment), the Functional Assessment of Cancer Therapy-General (FACT-G) quality of life scale and the Hospital Anxiety and Depression Scale at the end of each chemotherapy cycle (around day 10 post-chemotherapy).

Results

The sample consisted of 104 patients, primarily female, receiving anthracycline-based chemotherapy. While vomiting was minimal (5.2?C14.6?% of the patients), high levels of nausea were observed (55.2?C72.9?%), and severe nausea (>6 on a 0?C10 scale) was reported by 20.5?C29.2?% of the participants. Severe nausea had a borderline significant impact in relation to physical functioning (p?=?0.025) and a significant impact on nutritional status (severe acute nausea, p?=?0.003; severe delayed nausea, p?=?0.017). Clinically meaningful changes were observed in relation to the FACT-G total score.

Conclusion

Chemotherapy-induced nausea does have an impact on nutritional status and physical functioning and can impair anxiety and quality of life. As a key symptom associated with other symptoms, it is imperative that greater attention is given to managing treatment-related nausea through innovative non-pharmacological and nutritional interventions.     

Testing the ‘teachable moment’ premise: does physical activity increase in the early survivorship phase?

Purpose

Little is known about objectively measured physical activity during the early survivorship period. This study measured physical activity, fatigue, and quality of life (QOL) in breast cancer patients over the first year after completion of chemotherapy and compared results to a matched non-cancer group.

Methods

Data was obtained from 24 breast cancer subjects (mean ± SD) 50.9?±?12.8 years at time points of 6 weeks, 6 months and 1 year after completion of adjuvant chemotherapy and from 20 matched women. The following variables were assessed, physical activity (RT3 accelerometer and International Physical Activity Questionnaire), quality-of-life (EORTC QLQ C-30) and fatigue (Brief Fatigue Inventory).

Results

At 6 weeks after completion of chemotherapy, high levels of sedentary behaviour were found (6.8?±?1.9 h sedentary per day), which did not improve, and was no different to the comparison group (6.5?±?1.4 h). Less light activity was performed in the cancer cohort compared to the comparison group (p?=?0.003). Body mass index (BMI) increased significantly in the cancer cohort (p?=?0.015) and 1 year after chemotherapy finished only 13 % (n?=?3) had a BMI <25, while the comparable value was 45 % (n?=?9) in the non-cancer group. The QOL domain of cognitive function improved over the first 6 months (p?=?0.034) but physical functioning declined (p?=?0.008) over this time period. Fatigue did not change, and at the 1-year time point, 38 % of the cancer patients (n?=?11) reported high levels of fatigue.

Conclusion

This study highlighted the unchanging sedentary behaviour and weight gain of breast cancer survivors during the first year after completion of chemotherapy, which may inform rehabilitation models in this population.     

Differential expression of cytokines in breast cancer patients receiving different chemotherapies: implications for cognitive impairment research

Purpose

Altered levels of cytokines and chemokines may play a role in cancer- and cancer treatment-related cognitive difficulties. In many neurodegenerative diseases, abnormal concentrations of cytokines and chemokines affect neuronal integrity leading to cognitive impairments, but the role of cytokines in chemotherapy-related cognitive difficulties in cancer patients is not well understood. Patients receiving doxorubicin-based (with cyclophosphamide, or cyclophosphamide plus fluorouracil; AC/CAF) chemotherapy or cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy report experiencing cognitive difficulties; because these regimens work by different modes of action, it is possible that they differentially affect cytokine levels.

Methods

This study examined the relationships between cytokine levels (i.e., IL-6, IL-8, and MCP-1) and type of chemotherapy among 54 early-stage breast cancer patients receiving AC/CAF or CMF. Cytokine levels were assessed at two time-points: prior to on-study chemotherapy cycle?2 (cycle?2) and after two consecutive chemotherapy cycles (prior to on-study cycle?4; cycle?4).

Main results

Analyses of variance using cycle?2 levels as a covariate (ANCOVA) were used to determine differences between chemotherapy groups. Levels of IL-6, IL-8, and MCP-1 increased in the AC/CAF group and decreased in the CMF group; the only significant between-group change was in IL-6 (p?<?0.05).

Conclusions

These results, although preliminary based on the small sample size, suggest that AC/CAF chemotherapy is more cytokine inducing than CMF. Future studies should confirm these results and explore the distinct inflammatory responses elicited by different chemotherapy regimens when assessing cognitive function in cancer patients.