Rate Of Febrile Neutropenia Research Articles

Pegfilgrastim use and bone pain: a cohort study of community-based cancer patients.

Bone pain is a common adverse effect of the granulocyte colony-stimulating factors filgrastim and pegfilgrastim. However, the incidence of reported bone pain varies and therapies to mitigate this adverse effect are limited to case reports and one randomized controlled trial. The purpose of this study was to describe pegfilgrastim use, the incidence and treatment of bone pain, and rate of severe or febrile neutropenia among cancer patients receiving pegfilgrastim at a metropolitan, hospital-based, community cancer center. This retrospective chart review included the first 100 adult oncology patients who received at least one dose of pegfilgrastim from 1 January 2012 to 31 December 2012. Descriptive analyses were used to evaluate the primary and secondary outcomes. Of the identified cases, 69 cancer patients were evaluable. Most patients (74%) received pegfilgrastim for primary prophylaxis. Pegfilgrastim-associated bone pain occurred in 19% and loratadine was the most common medication used to treat it. Among the patients who received pegfilgrastim for primary prophylaxis, 8% were hospitalized for febrile neutropenia. Among those hospitalized for febrile neutropenia, 64% had not received pegfilgrastim for primary prophylaxis. Pegfilgrastim is commonly used for primary prophylaxis during the first cycle of chemotherapy. Hospitalizations for febrile neutropenia occurred most commonly among patients without primary prophylaxis. Pegfilgrastim-associated bone pain occurred in a similar percentage, as reported in randomized controlled trials but less than that reported by survey. Loratadine was the most commonly employed medication to mitigate this adverse effect.

Abstract P3-12-07: A multicenter randomized double-blind phase III clinical trial to evaluate the efficacy and safety of GCPGC, a novel pegylated G-CSF in patients receiving DA or TAC chemotherapy for breast cancer compared to peg-filgrastim

Abstract Introduction Treatment with cytotoxic chemotherapy is known to be associated with a significant risk of febrile neutropenia. GCPGC(Green Cross Co., Korea) is a novel long acting recombinant human granulocyte colony-stimulating factor (G-CSF) analog that reduces the severity and duration of neutropenia. We conducted a phase III trial to evaluate the efficacy and safety of GCPGC compared to pegfilgrastim. Methods A total of 117 patients were enrolled in this multicenter, phase III, double-blind randomized trial between Feb 2012 and May 2013. They were randomly assigned to receive either GCPGC or pegfilgrastim during the maximal 6 cycles of chemotherapy which consisted of DA (docetaxel and doxorubicin) or TAC (docetaxel, doxorubicin, and cyclophosphamide). Based on the results of the phase II dose-finding study for GCPGC, the dose of 6 mg was selected. Both medications were administered 24 hours after the completion of each cycle of chemotherapy. The primary efficacy endpoint of this study was the duration of grade 4 neutropenia (Absolute Neutrophil Count (ANC) <500/mm3) during the first cycle of chemotherapy. Secondary endpoints included the time to ANC recovery during the first cycle of chemotherapy, which was defined as the number of days required for neutrophil counts to exceed 2,000/mm3, the rate of febrile neutropenia, the rate of severe neutropenia which persisted for more than three days during first cycle of chemotherapy, the depth of ANC nadir, the ANC level on day 7 after each cycle of chemotherapy, the frequency of dose reduction or delay, the number of hospitalization related to febrile neutropenia after the first cycle of chemotherapy, and the number of treatment with intravenous antibiotics. Results A total of 116 patients were evaluable for safety and 115 patients were evaluable for efficacy. The intention-to-treat analysis showed that there was no statistical difference between GCPGC and pegfilgrastim in terms of the duration (days) of grade 4 neutropenia in chemotherapy cycle 1 (1.64±1.18 vs 1.80±1.05; difference -0.15±1.11 [97.5% C.I. -, 0.26]; the pre-specified non-inferiority margin of 1.0). Notably, patients treated with GCPGC had a statistically significant reduction in the time to recovery from neutropenia (ANC >2,000/mm3), one of the secondary endpoints of the study, compared to those treated with pegfilgrastim (8.85 ± 1.45 vs. 9.83 ± 1.20 days; p <0.0001). There was no difference between groups regarding the other secondary endpoints. In addition, no significant differences were observed between the safety profiles of the two groups. Conclusion Collectively, GCPGC is not inferior to peg-filgrastim and represents an effective alternative for reducing the duration of neutropenia in breast cancer patients receiving TAC or DA chemotherapy. Citation Format: Joo Han Lim, Ki-Hyeong Lee, Keon-Uk Park, In-Hae Park, Eun Kyung Cho, Moon Hee Lee, So-Young Yoon, Jee-Hyun Kim, In-Sil Choi, Jae-Hoo Park, Young-Jin Choi, Hee-Jun Kim, Kyung Hae Jung, Si-Young Kim, Do-Youn Oh, Seock-Ah Im. A multicenter randomized double-blind phase III clinical trial to evaluate the efficacy and safety of GCPGC, a novel pegylated G-CSF in patients receiving DA or TAC chemotherapy for breast cancer compared to peg-filgrastim [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-12-07.

Multi-institutional experience with FOLFIRINOX in pancreatic adenocarcinoma.

Combination chemotherapy with FOLFIRINOX (oxaliplatin, irinotecan, fluorouracil, and leucovorin) was shown to be effective in a large phase III trial. The purpose of this study was to examine the tolerance and effectiveness of FOLFIRINOX as practiced outside of the confines of a clinical trial and to document any dose modifications used by practicing oncologists. Data on patients with all stages of pancreatic adenocarcinoma treated with FOLFIRINOX at three institutions was analyzed for efficacy, tolerance, and use of any dose modifications. Total of 61 patients was included in this review. Median age was 58 years (range: 37 to 72 years), 33 were male (54.1%) and majority had ECOG performance of 0 or 1 (86.9%, 53 patients). Thirty-eight (62.3%) had metastatic disease, while 23 (37.7%) were treated for locally advanced or borderline resectable disease. Patients were treated with a median number of four cycles of FOLFIRINOX, with dose modifications in 58.3% (176/302) of all cycles. Ten patients had stable disease (16.4%), four had a partial response (6.6%) while eight had progressive disease (13.1%) on best imaging following therapy. Median progression-free survival and overall survival were 7.5 months and 13.5 months, respectively. The most common grade 3-4 adverse event was neutropenia at 19.7% (12 cases), with 4.9% (3 cases) rate of febrile neutropenia. Twenty-one patients (34.4%) were hospitalized as a result of therapy but there were no therapy-related deaths. Twenty-three (37.7%) had therapy eventually discontinued as a result of adverse events. Despite substantial rates of adverse events and use of dose modifications, FOLFIRINOX was found to be clinically effective in both metastatic and non-metastatic patients. Regimen toxicity did not detract from overall response and survival.

Cost-effectiveness of prophylactic granulocyte colony-stimulating factor for febrile neutropenia in breast cancer patients receiving FEC-D.

5-fluorouracil, epirubicin, cyclophosphamide→docetaxel (FEC-D) has been associated with higher-than-expected rates of febrile neutropenia (FN) that meet the current guideline threshold of 20% for primary prophylaxis (PP) with granulocyte colony-stimulating factor (G-CSF). We examined the cost-effectiveness of FEC-D with varying strategies of G-CSF prophylaxis from the perspective of the public payer in Ontario, Canada. A state-transition model was developed to compare three strategies: FEC-D with secondary prophylaxis (SP) only, PP starting with the first cycle of D, and PP starting with the first cycle of FEC. Analysis was conducted for a hypothetical cohort of 50-year-old early-stage breast cancer patients undergoing adjuvant chemotherapy, at a 10-year horizon. Results were expressed in quality-adjusted life-years (QALYs) and 2013 Canadian dollars. Costs and benefits were discounted at 5%. Event rates, costs, and utilities were derived from the literature. One-way and probabilistic sensitivity analyses were conducted. Using filgrastim, the incremental cost-effectiveness ratios (ICERs) for starting PP with the first cycle of D and starting PP with the first cycle of FEC, compared to using SP only, were $57,886/QALY and $116,186/QALY, respectively. With pegfilgrastim, the ICERs for the same strategies were $90,735/QALY and $149,483/QALY. Compared to using filgrastim SP only, starting PP with D had a 24% chance of being cost-effective at a willingness-to-pay (WTP) threshold of $50,000/QALY, and a 99% chance at a WTP threshold of $100,000/QALY. Results were sensitive to FN-related parameters, such as the risk of FN per cycle with D and the associated mortality, but were robust to uncertainty in parameters related to breast cancer, such as the utilities and hazard of relapse. FEC-D with PP starting with the first cycle of D is most likely to be cost-effective, especially with increased risk of FN and mortality from FN.

FOLFIRINOX chemotherapy in locally advanced and metastatic pancreatic adenocarcinoma: A retrospective analysis of toxicity and outcomes.

436 Background: The FOLFIRINOX chemotherapy regimen has been shown to improve overall survival in patients with metastatic pancreatic cancer, however, toxicity is increased. The aim of this analysis was to assess the tolerability and outcomes of this regimen in clinical practice. Methods: A retrospective analysis of patients treated with FOLFIRINOX chemotherapy in a tertiary referral centre between January 2013 and May 2014 was conducted. Toxicity was graded as per CTCAE version 4.0. Overall survival and tumour response were analysed. Results: A total of 80 patients were identified with locally advanced or metastatic disease in 47 and 33 cases respectively. The median patient age was 63 (range 30 –79) and the median number of cycles delivered was 6 (range 1-12). G3/4 neutropenia was recorded in 12.5% of patients, with a febrile neutropenia rate of 9.9%. G3/4 nausea and vomiting was reported in 17.5% and G3/4 diarrhoea in 15% of cases. G3/4 electrolyte disturbance occurred in 5%. Response rates assessed after 3-6 cycles showed PR 26%, SD 31% and PD 25%. Median duration of follow up for survivors is 8.7 months (range 3.6 – 20.8). Median OS is 11.4 months (95% CI 10.1 – 12.7). Median OS was reported as 11.4 months, 10.9 months and 2.3 months according to baseline PS 0, 1 and 2 respectively (log rank p <0.001). Conclusions: FOLFIRINOX can be safely delivered out with a trial cohort. Outcomes are strongly influenced by patient PS and careful patient selection is critical.

Effects of Traditional Chinese Medicine on Chemotherapy-Induced Myelosuppression and Febrile Neutropenia in Breast Cancer Patients.

Title. Chemotherapy-induced myelosuppression lowers the quality of life in breast cancer patients and causes many complications. Traditional Chinese Medicine (TCM) is a widely used complementary and alternative medicine therapies. Objective. To study whether TCM can reduce the incidence of chemotherapy-induced leukopenia, neutropenia, and febrile neutropenia (FN) in breast cancer patients. Methods. The data were analyzed retrospectively between patients who received TCM treatment (group 1, n = 453) and patients who did not receive TCM treatment (group 2, n = 359). Significant risk factors associated with the occurrence of chemotherapy-induced leukopenia, neutropenia, and FN were identified using multivariate analysis. Propensity score-matched patients were analyzed to adjust for any baseline differences. Results. Group 1 patients had a significantly lower rate of chemotherapy-induced severe leukopenia, neutropenia, and FN, compared with group 2 (43% versus 71%, P < 0.0001, 72% versus 78%, P = 0.005, 6% versus 24%, P < 0.0001, resp.). Multivariate analysis revealed that chemotherapy regimens containing anthracyclines combined with paclitaxel or docetaxel were the most significant predictor. Subgroup analysis indicated that TCM treatment showed benefit in relieving chemotherapy-induced leukopenia and FN in most chemotherapy regimens. Conclusions. TCM treatment could lower the risk of severe chemotherapy-induced leukopenia, neutropenia, and FN in breast cancer patients.

Comparison of filgrastim and pegfilgrastim to prevent neutropenia and maintain dose intensity of adjuvant chemotherapy in patients with breast cancer.

The aim of this study was to compare the effectiveness of prophylactic single fixed dose of pegfilgrastim and daily administration of filgrastim on febrile neutropenia (FN), severe neutropenia, treatment delay, and dose reduction in patients with breast cancer receiving dose-dense adjuvant chemotherapy. A retrospective cohort study with 1058 breast cancer patients matched by age and chemotherapy was conducted. The primary endpoints were FN, severe (grade 3, 4) neutropenia, dose reduction (>10 % reduction of the dose planned), and treatment delay (dose given more than 2 days later). Eighteen episodes of FN (3.4%) in the filgrastim group and 23 (4.3%) in the pegfilgrastim group (p = 0.500) were recorded. More than half of the total episodes (27/41) occurred during the first 4 cycles of treatment. Patients who received filgrastim were almost three times more likely to experience a severe neutropenia episode and were significantly more likely to experience a dose reduction (18.5%) compared to those who received pegfilgrastim (10.8%) (p < 0.001). The percentage of patients, who received their planned dose on time, was significantly lower in patients receiving filgrastim (58%) compared to those receiving pegfilgrastim (72.4%, p < 0.001). No significant difference was detected on FN rate between daily administration of filgrastim and single administration of pegfilgrastim. However, patients receiving pegfilgrastim had a significantly lower rate of severe neutropenia, as well as dose reduction and treatment delay, thus, achieving a higher dose density.

Azacitidine (AZA) Versus Conventional Care Regimens (CCR) in Older Patients with Newly Diagnosed Acute Myeloid Leukemia (>30% Bone Marrow Blasts) with Morphologic Dysplastic Changes: A Subgroup Analysis of the AZA-AML-001 Trial

Azacitidine (AZA) Versus Conventional Care Regimens (CCR) in Older Patients with Newly Diagnosed Acute Myeloid Leukemia (>30% Bone Marrow Blasts) with Morphologic Dysplastic Changes: A Subgroup Analysis of the AZA-AML-001 Trial

Efficacy and toxicity of abiraterone and docetaxel in octogenarians with metastatic castration-resistant prostate cancer.

To assess the efficacy and toxicity of abiraterone and docetaxel in men with metastatic castration-resistant prostate cancer (mCRPC) of age >80 compared to younger men. Retrospective chart review of 116 men treated with abiraterone and 378 men treated with docetaxel at Princess Margaret Cancer Centre. Categorical outcome measures including PSA response rate (PSA-RR) and incidence of toxic side-effects were compared using Fisher's exact test. Overall survival (OS) and biochemical progression free survival (bPFS) were analyzed using the Kaplan-Meier method and log-rank tests. Thirty-four (29%) and 50 (13%) of the men treated with abiraterone or docetaxel, respectively, were octogenarians. For abiraterone there were no significant differences in PSA-RR (42% vs. 39%), bPFS (4.7 vs. 4.4months) or OS (14.0 vs 20.7months) between octogenarians and younger men, respectively. Toxicity was mild with no significant differences between age groups. For men treated with docetaxel PSA-RR and OS did not differ between age groups (40% vs. 45% and 12.0 vs. 14.1months, respectively). However, rates of febrile neutropenia were 16% and 7% for octogenarians and younger men, respectively (p=0.048). This difference was observed despite greater use of lower dose intensity and weekly docetaxel in the elderly cohort, with 20% of them receiving lower than standard dose during their first cycle compared to 7% of younger men (p=0.004). Treatment outcome on abiraterone and docetaxel did not differ in patients over and under the age of 80, but febrile neutropenia was more common in octogenarians treated with docetaxel despite lower dose intensity.

Rates of febrile neutropenia with pegfilgrastim on same day versus next day of CHOP with or without rituximab.

Febrile neutropenia is a complication of myleotoxic chemotherapy that can markedly decrease quality of life and increase healthcare costs. A granulocyte-colony stimulating factor (G-CSF) is used to increase neutrophil production to reduce the risk of developing febrile neutropenia. However, G-CSF administered on the same day as chemotherapy can worsen and prolong neutropenia. To study and compare the effects of pegfilgrastim on the incidence of febrile neutropenia and grade 4 neutropenia in patients receiving pegfilgrastim on the same day (day 1) versus the next day (day 2 or beyond) of chemotherapy, a retrospective, single-center, nonrandomized, cohort study was carried out of adult non-Hodgkin's lymphoma patients who received pegfilgrastim 6 mg subcutaneously on day 1 or beyond of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) with or without rituximab every 3 weeks. Six hundred and fifty-five chemotherapy cycles (320 cycles for the same day and 335 cycles for the next day) were evaluable in 141 patients. Among all cycles, the incidence of febrile neutropenia was 9.4 versus 5.1% in the same-day versus the next-day group (P=0.03). The incidence of febrile neutropenia was the highest after the first cycle in the same-day group, which was 19.4, versus 11.1% for the next-day group (P=0.27). There were three deaths among patients who developed febrile neutropenia, including two in the next-day group versus one in the same-day group. In conclusion, our findings support the need for a randomized phase III study to fully evaluate whether a G-CSF is safer when administered on the next day versus the same day of chemotherapy.

624P - Weekly Versus Biweekly Combination of Docetaxel (D)-Cisplatin (C)-5Fu (F) in Advanced Gastric Cancer and Esogastric Junction Adenocarcinoma (Agc): Doge Study

ABSTRACT Aim: Triweekly DCF is a standard treatment in aGC, but is, however, associated with a bleak 30% febrile neutropenia (FN) incidence requiring prophylactic administration of granulocyte-colony stimulating factor (G-CSF). The DoGE study aims to define efficient but less toxic alternate DCF combinations. Methods: Chemonaive patients (pts) with aGC, age ≥ 18, PS ≤1 and normal organ function were randomized in a multicentric phase II trial (EudraCT 2008-000551-10) between a weekly (D 40 mg/m2,C 35 mg/m2, folinic Acid (FA) 400 mg/m2, F 1800 mg/m2 24 h infusion on days 1 and 8 every 3 weeks (wks), arm 1) and a biweekly regimen (D 50 mg/m2, C 50 mg/m2, FA 400 mg/m2, F 2000 mg/m2 48 h infusion every 2 wks, arm 2). G-CSF was allowed only as secondary prevention. The tumors were assessed every 6 wks. A Briant & Day two -teps design with toxicity and rate of non-progressive disease as primary endpoints was used. Insufficient efficacy was defined as 6 wks-disease control rate (DCR) 25% FN (b = 10% and a = 10% for activity, 15% for toxicity). Results: Between Oct 2008 and Oct 2013, 106 pts were recruited in 15 centers: 76 males (71.7%), PS 0/1: 60 (57%)/46 (43%), median age 62(33-85). Early study closure due to slow accrual led to a reduced 80% power. Among the 103 pts who received the study medications (52 arm 1 and 51 arm 2), 77% and 86% experienced grade III-IV toxic reactions, mainly neutropenia (21%,95% CI 12-34 in arm 1 vs 59%, 95% CI 45-71 in arm 2), and similar fatigue (27% vs 25%), anorexia (19% vs 18%) and diarrhea (15% vs 12%) in both arms. The 6 wks-DCR was 83%, 95% CI 71-91 in arm 1 and 79%, 95% CI 67-88 in arm 2. The pts' outcomes are reported hereunder. Regimen Grade III-IV toxicities * FN at 6 wks * Toxic deaths * mOS¶ mPFS¶ Weekly (arm1) 77 (64-86) 9.6 (4-21) 9 (4-20) 8.2 (6.0-14.5) 5.1 (3.2-6.5) Biweekly (arm2) 86 (74-93) 6 (2-16) 4 (1-13) 11.9 (7.4-15.9) 5.2 (3.0-6.9) * in % (95% CI); ¶ in months (95% CI) Conclusions: Weekly and biweekly DCF meet the study's safety requirements with less than 10% FN rate without G-CSF support. Both regimens have adequate efficacy according to the study design, consistent with the literature findings on the triweekly regimen, and represent valuable alternatives for further clinical development. Disclosure: All authors have declared no conflicts of interest.

Results of Interim Analysis of Prospective Randomized Multicenter Open-Label Study in Comparison of Efficacy and Toxicity of Beacopp-14 and Beacopp-Esc Regimens in Patients with Hodgkin'S Lymphoma from Poor-Prognosis Group

ABSTRACT Aim: The aim of the study was to evaluate overall response rate (ORR), complete response rate (CRR), 3-year overall survival (OS), and toxicity of BEACOPP-14 and BEACOPP-esc regimens. Methods: Since September 2008 until December 2013 215 patients from 18 to 65 years old (median 30 years), 90 male and 125 female with stage ІІВ with 1 unfavorable factor and stage III-IV. Patients were randomized to receive ВЕАСОРР-14 (98 patients) or ВЕАСОРР-esc (117 patients). The treatment efficacy in both groups was evaluated by Сheson criterion (1999, 2007). Toxicity rates were evaluated according to NCI-CTC V.3.0. After completion of chemotherapy patients with initial sites >5 cm, residual lymph nodes >2 cm and PET-positive sites received radiotherapy (30-36 Gy). Results: Both groups were similar by clinical and laboratory characteristics. ORR was 98.0% in the group of BEACOPP-14 and 98.3% in the group of BEACOPP-esc. CRR was 81% in the group of BEACOPP-14 and 73.5%, in the group of BEACOPP-esc, р > 0.05. Maximal observation period was 72 months, median 32 months. 3-year OS in the group of BEACOPP-14 was 94.2% vs 92.6% in the group of BEACOPP-esc, p > 0.05. Toxicity was observed in 62.4% of cycles in the group of BEACOPP-14 and in 57.8% cycles in the group of BEACOPP-esc, p > 0.05. 3 patients had died in the group of BEACOPP-esc due to toxicity. There was no difference in haematological toxicity grade 3-4 in both groups: anemia was observed in 16% of cases in the group of BEACOPP-14 vs 14% of cases in the group of BEACOPP-esc, thrombocytopenia – in 3% of cases in both groups (p> 0.05), neutropenia – in 45% vs 41% of cases, respectively (p Conclusions: During the interim analysis of our study any significant difference in efficacy of BEACOPP-14 and BEACOPP-esc regimens were not revealed. The rate of neutropenia gr. 3-4 was significantly higher in the group of BEACOPP-14 than in the group of BEACOPP-esc. This didn't influence the rate of febrile neutropenia and infections. The further analysis will allow making the final conclusion in comparison of the efficacy and toxicity of BEACOPP-14 and BEACOPP-esc. Disclosure: All authors have declared no conflicts of interest.

Febrile neutropenia risk with adjuvant TC (docetaxel and cyclophosphamide) regimen: Experience of Brazilian cancer centers.

e12002 Background: In patients diagnosed with Breast Cancer (BC), adjuvant chemotherapy is an important treatment strategy toreduce risk of breast and systemic recurrence, as well as cancer death. The combination of Docetaxel and Cyclophosphamide (TC) is a well-recognized effective regimen. Nonetheless, a considerable high rate of febrile neutropenia (FN) may be associated with this regimen. We sought to investigate hematologic toxicity associated with adjuvant TC in a non-selected cohort of BC patients. Methods: We reviewed the electronic medical records of patients who presented to the Oncology Center from Hospital Sirio-Libanes (HSL) and Instituto do Cancer do Estado de Sao Paulo (ICESP) after definitive breast surgery to initiate adjuvant chemotherapy with TC. Results: 95 patients with early BC were included in our analysis. Median age was 55.5 years. All patients had a good performance status (Ecog 0 or 1) and the great majority of them had no comorbidities. Four chemotherapy cycles were given for mo...

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.

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 ≥19 years old, with advanced HNC who received DCF induction chemotherapy (D and P 75 mg per meter squared (mg/m(2)) on day 1 and 5-FU 750 mg/m(2)/day from D1 to D5), were included in the analysis. 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). Early administration of G-CSF is safe and seems to be more effective than D7. Future prospective trials are required to confirm our results.

Cefpodoxime for Antimicrobial Prophylaxis in Neutropenia: A Retrospective Case Series

BackgroundAntimicrobial prophylaxis in select neutropenic patients has reduced fever, infection rates, hospital length of stay, and hospitalization rates. Guidelines from the Infectious Diseases Society of America recommend the consideration of prophylaxis with a fluoroquinolone in patients at high risk for infection after chemotherapy. The use of fluoroquinolones has been associated with many adverse events, and there is limited evidence on alternative antimicrobial prophylaxis in patients intolerant of fluoroquinolones. ObjectivesOur study describes a single-center experience of cefpodoxime as an alternative to fluoroquinolones for antibacterial prophylaxis during neutropenia after chemotherapy and represents a retrospective evaluation of an oral cephalosporin in adult patients for this purpose. MethodsThis retrospective case series analyzed data from the electronic medical records of 41 patients having hematologic malignancies and given cefpodoxime for neutropenic prophylaxis. ResultsThe rate of febrile neutropenia was 85%, with 60% culture-positive infections. Gram-positive organisms were identified in 52% of positive cultures, and gram-negative organisms represented 40% of positive cultures. Antimicrobial resistance to guideline-recommended empiric treatment regimens was not seen in breakthrough infections. ConclusionsCefpodoxime can be utilized for prophylaxis, without adversely affecting resistance to broad-spectrum agents, and maintains a high level of appropriateness of guideline-recommended empiric regimens. This study of cefpodoxime prophylaxis in adult patients intolerant to fluoroquinolones adds to the literature of potential alternative agents for prophylaxis in neutropenic patients.

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

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. 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. 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). 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.

A phase III randomized trial of high‐dose CEOP + filgrastim versus standard‐dose CEOP in patients with non‐Hodgkin lymphoma: 10‐year follow‐up data: Australasian Leukaemia and Lymphoma Group (ALLG) NHL07 trial

Increasing dose intensity (DI) of chemotherapy for patients with aggressive non-Hodgkin lymphoma (NHL) may improve outcomes at the cost of increased toxicity. This issue was addressed in a randomized trial aiming to double the DI of myelosuppressive drugs. Between 1994 and 1999, 250 patients with previously untreated aggressive NHL were randomized to treatment with six cycles of 3-weekly standard (s) or intensive (i) chemotherapy: s-CEOP-cyclophosphamide 750, epirubicin 75, vincristine 1.4 mg/m(2) all on day 1, and prednisolone 100 mg days 1-5; i-CEOP-cyclophosphamide 1,500, epirubicin 150, vincristine 1.4 mg/m(2) all on day 1, and prednisolone 100 mg days 1-5. Primary endpoint was 5-year overall survival (OS). Relative to s-CEOP patients, i-CEOP patients achieved a 78% increase in the DI of cyclophosphamide and epirubicin. Despite this, there was no significant difference in any outcome: 5-year OS (56.7% i-CEOP; 55.1% s-CEOP; P = 0.80), 5-year progression free survival (PFS; 41% i-CEOP; 43% s-CEOP; P = 0.73), 5-year time to progression (TTP; 44% i-CEOP; 47% s-CEOP; P = 0.72), or complete remission (CR) + unconfirmed CR (CRu) rates (53% i-CEOP; 59% s-CEOP; P = 0.64). Long-term follow up at 10 years also showed no significant differences in OS, PFS, or TTP. The i-CEOP arm had higher rates of febrile neutropenia (70 vs. 26%), hospitalisations, blood product utilisation, haematological and gastrointestinal toxicities, and lower quality of life scores during treatment, although without significant differences 6-month later. In the treatment of aggressive NHL in the prerituximab era, increasing DI did not result in improved outcomes, while at the same time lead to increased toxicity.

Epidemiology and natural history of central venous access device use and infusion pump function in the NO16966 trial

Background:Central venous access devices in fluoropyrimidine therapy are associated with complications; however, reliable data are lacking regarding their natural history, associated complications and infusion pump performance in patients with metastatic colorectal cancer.Methods:We assessed device placement, use during treatment, associated clinical outcomes and infusion pump perfomance in the NO16966 trial.Results:Device replacement was more common with FOLFOX-4 (5-fluorouracil (5-FU)+oxaliplatin) than XELOX (capecitabine+oxaliplatin) (14.1% vs 5.1%). Baseline device-associated events and post-baseline removal-/placement-related events occurred more frequently with FOLFOX-4 than XELOX (11.5% vs 2.4% and 8.5% vs 2.1%). Pump malfunctions, primarily infusion accelerations in 16% of patients, occurred within 1.6–4.3% of cycles. Fluoropyrimidine-associated grade 3/4 toxicity was increased in FOLFOX-4-treated patients experiencing a malfunction compared with those who did not (97 out of 155 vs 452 out of 825 patients), predominantly with increased grade 3/4 neutropenia (53.5% vs 39.8%). Febrile neutropenia rates were comparable between patient cohorts±malfunction. Efficacy outcomes were similar in patient cohorts±malfunction.Conclusions:Central venous access device removal or replacement was common and more frequent in patients receiving FOLFOX-4. Pump malfunctions were also common and were associated with increased rates of grade 3/4 haematological adverse events. Oral fluoropyrimidine-based regimens may be preferable to infusional 5-FU based on these findings.

Chemomobilization with high‐dose etoposide and G‐CSF results in effective and safe stem cell collection in heavily pretreated lymphoma patients: report from a single institution study and review

The optimal mobilization strategy prior to autologous stem cell transplantation (auto-SCT) for patients with lymphoma is yet to be determined. We reviewed our institutional experience using chemomobilization with high-dose (HD) etoposide (1.6 g/m(2) ) and G-CSF (300 μg/day) in 79 patients with lymphoma. The majority (76%) had received at least two prior regimens of chemotherapy, and 12 (15.2%) patients had previously failed to mobilize following HD cyclophosphamide or DHAP or ICE with G-CSF. HD etoposide and G-CSF chemomobilization resulted in successful collection (>2 × 10(6) CD34+ cells/kg) in 82.3% of patients within a median 2 (1-6) apheresis days. Patients had stem cells collected between days +8 and +15, with a median +12 day. Median total CD34+ cells/kg collected was 5.95 × 10(6) (0.1-36.8). Seventy-one percent of patients yielded >2 × 10(6) CD34+ cells/kg in ≤2 d of apheresis and were defined as good mobilizers. While median CD34+ cells/kg collected for good mobilizers was 7.6 × 10(6) , it was 2.6 × 10(6) for poor mobilizers (P < 0.001). This regimen was safe with a low rate of febrile neutropenia (7.6%) and acceptable rates of RBC (40.5%) and platelet transfusions (22.8%). Hematopoietic recovery after auto-SCT was achieved on expected time. Therapy-related myelodysplastic syndrome/acute myeloid leukemia occurred in only one patient (1.3%) with in a median follow-up of 16 months after chemomobilization. We conclude that HD etoposide and G-CSF chemomobilization appear to result in effective, tolerable, and safe stem cell collection in the majority of heavily pretreated lymphoma patients.

Patient risk factors and pegfilgrastim use in cabazitaxel-treated prostate cancer pateints in an academic setting.

224 Background: Cabazitaxel can offer a survival advantage in patients (pts) with metastatic castration resistant prostate cancer (mCRPC). Febrile neutropenia (FN) has emerged as a serious complication, with a rate of 8% in the TROPIC trial (de Bono, Lancet 2010). Prophylaxis with pegfilgrastim (P) can decrease the risk of FN, although predictors of FN continue to evolve. We performed an analysis on the effect of prophylactic P use on FN and the impact of certain risk factors on FN rates. Methods: We conducted a retrospective analysis of mCRPC patients treated with cabazitaxel from June 2010 to August 2013 at Dana-Farber Cancer Institute. Patient clinical and treatment variables were extracted. Fisher’s exact test was used to evaluate the association between potential risk factors and FN. Results: A total of 89 patients were treated at our institution and included in this analysis. All patients received at least one dose of cabazitaxel and received a mean of four cycles. Five pts (5.6%) developed FN; 3 out of 70 (4.3%) receiving P and 2 out of 19 (10.5%) not receiving P (p=0.3). Of the 24 patients that started cabazitaxel at a reduced dose, none developed FN. No toxic death was reported. Among several risk factors including P use, age older than 65, pre-existing neutropenia, prior chemotherapy, pre-existing infection, poor performance status, liver and renal dysfunction, and recent surgery, only a prior history of palliative radiation had a significant association with FN (p=.002). Conclusions: The rate of FN in a large academic practice is similar to what was reported in the TROPIC trial. Prior radiation may be a risk factor for FN in cabazitaxel-treated mCRPC patients. Other factors that may help better predict the risk of FN in different groups of patients receiving cabazitaxel must be identified.