Febrile Neutropenia In Breast Cancer Patients Research Articles

A randomized trial of pegylated recombinant human granulocyte-colony stimulating factor to prevent febrile neutropenia in breast cancer after chemotherapy.

e12516 Background: The purpose of this study was to evaluate the incidence of febrile neutropenia (FN) in breast cancer patients with pegylated recombinant human granulocyte-colony stimulating factor (PEG-rhG-CSF) administration at 48 or 24 hours after chemotherapy for primary prevention. Methods: Patients with stage I-III invasive breast cancer who were scheduled to receive 4 cycles of adjuvant chemotherapy with EC regimen (epirubicin combined with cyclophosphamide) were eligible for this multicenter, open-label, randomized trial. Patients were randomized (1:1) to receive PEG-rhG-CSF (Jinyouli) 48 hours (48h group) or 24 hours (24h group) after the end of each cycle of chemotherapy. The primary endpoint was the incidence rate of FN. The secondary endpoints included the incidence rates of grade 3/4 neutropenia, chemotherapy dose reduction and chemotherapy delay due to neutropenia, antibiotic administration, the pain (bone, muscle, or joint), and the relative dose intensity (RDI) of the chemotherapy. Results: The preliminary results enrolled 197 patients including 96 in the 48h group and 101 in the 24h group. 78.1% of 48h group patients and 73.3% of 24h group patients completed four cycles of chemotherapy. The incidence rates of FN were 2.1% in the 48h group and 4.0% in the 24h group respectively. FN occurred in the first two cycles in the 48h group, while in the 24h group, it occurred only in the first cycles. The incidence rate of grade 3/4 neutropenia was 27.1% in the 48h group and 51.5% in the 24h group respectively. There was no delay in chemotherapy due to neutropenia in the two groups. The incidence rate of chemotherapy dose reduction due to neutropenia was 2.1% in the 48h group and 1.0% in the 24h group respectively. 2 (2.1%) patients in the 48h group and 4 (4.0%) patients in the 24h group received antibiotics. The mean RDI of each cycle of chemotherapy was 91.3% in the 48h group and 91.5% in the 24h group, respectively. The incidence rate of all grades pain (bone, muscle, or joint) was 25.0% in the 48h group, and 20.8% in the 24h group. With regard to 3 or higher grade pain, 1 (1.0%) patient in the 48h group experienced bone pain and 1 (1.0%) patient in the 24h group experienced muscle pain. Conclusions: Preliminary results suggest a similar effect of PEG-rhG-CSF administration at 48 or 24 hours after chemotherapy in primary prevention of FN in breast cancer patients receiving EC chemotherapy regimen. Recruitment is ongoing and updated data will be presented. Clinical trial information: ChiCTR1800019516. [Table: see text]

Efficacy and safety of pegfilgrastim in prophylaxis of chemotherapy-induced neutropenia in breast cancer patients.

e12511 Background: The role of secondary prophylaxis with pegfilgrastim (brand name: Jinyouli) in Chinese breast cancer patients has not been fully evaluated. We assessed the efficacy and safety of pegfilgrastim in secondary prophylaxis of chemotherapy-induced neutropenia in breast cancer patients. Methods: In the open-label, single-arm, multicenter trail, 319 patients were enrolled. Breast cancer patients who developed grades 3/4 neutropenia in the previous chemotherapy cycle were given a fixed dose of subcutaneous pegfilgrastim, 24-48 hours after receiving the same chemotherapy regimen in the subsequent cycle. A dose of 6mg/cycle was given to patients weighed ≥45kg, and a dose of 3mg/cycle was given to patients weighed <45kg. The primary end point was the incidence of grade 3/4 neutropenia and secondary end point was the incidence of febrile neutropenia (FN). Results: In patients who received prophylactic pegfilgrastim, the incidence of grade 3/4 neutropenia was reduced to 12.53% (95% CI, 9.1 to 16.7) and the incidence of FN was reduced from 6.58% (95% CI, 4.1 to 9.9) in the screening cycle to 0.94% (95% CI, 0.2 to 2.7)(Table). Among the 40 patients who still developed grades 3/4 neutropenia after receiving pegfilgrastim, the absolute neutrophil count (ANC) was not significantly different between patients with (n=10) or without (n=30) additional filgrastim treatment. The most common adverse events (AEs) associated with pegfilgrastim were bone pain and myalgia, which were prevalent in 10% to 15% of the patients. However, both AEs were mild or moderate (grades 1/2). Conclusions: Prophylactic administration of pegfilgrastim is effective and safe in reducing the risk of grades 3/4 neutropenia and FN in breast cancer patients after receiving chemotherapy. [Table: see text]

Abstract P5-14-09: Prospective cohort study of febrile neutropenia in breast cancer patients with neoadjuvant and adjuvant chemotherapy: CSPOR-BC FN Study

Abstract Background: Febrile neutropenia (FN) is one of the greatest concerns when maintaining chemotherapy dosage for early breast cancer patients. However, the incidence proportion of FN remains unclear because of the empirical prescription of oral antibiotics, the use of G-CSF, and the absence of body temperature examination and hematology test. Therefore, we performed a prospective cohort study of FN in breast cancer patients receiving adjuvant or neoadjuvant chemotherapy. Methods: Breast cancer patients were prospectively enrolled from August 2015 to July 2017. The regimens included 4 cycles of FEC (epirubicin 100 mg/m²), E(A)C (epirubicin 90 mg/m² or doxorubicin 60 mg/m²), and TC (docetaxel 75 mg/m²). Considering the current practice of empirically prescribing oral antibiotics without hematology tests, we followed 2 groups and surveyed FN using 2 different definitions: true FN (T-FN): ≥ 37.5°C and grade 4 neutropenia by a hematologic test with a visit to the hospital (visiting group), and surrogate FN (S-FN): ≥ 37.5°C and oral antibiotic intake without a mandatory visit to the hospital (non-visiting group). The primary objective was to investigate the FN incidence of each regimen during the first 4 cycles. The overall incidence proportion of FN was calculated as (patients with T-FN or S-FN) / (total patients). The proportion of T-FN or S-FN in each group was also examined. In the secondary analysis, the risk factors of FN and the safety of FN management in the non-visiting group were investigated. Multiple logistic regression analysis was performed to assess the risk factors. As we assumed that FN occurs in 20% of the patients by these regimens, the planned sample size based on the confidence intervals was 1000. This trial was registered as UMIN 000017857. Results: A total of 1005 female patients with Stage I to III breast cancer were enrolled. Of these patients, 25 were excluded because of incomplete treatments or other regimens administered. There were 477 patients in the visiting group and 503 patients in the non-visiting group. The numbers of patients in each regimen were 338 in FEC, 335 in E(A)C, and 307 in TC. The overall incidence proportions of FN were 22.5%, 27.5%, and 33.9% in FEC, E(A)C, and TC, respectively. The incidence proportions of T-FN were 27.7%, 22.4%, and 36.6%; those of S-FN were 17.3%, 32.4%, and 31.5%. Pegfilgrastim (PEG-G) was used in the 1st cycle more frequently in the non-visiting group than in the visiting group: in FEC, E(A)C, and TC, 39.0%, 11.8%, and 52.1% in the non-visiting group; 4.71%, 1.82%, and 14.1% in the visiting group, respectively. The risk factors of FN were regimen (TC: OR: 2.67, 95%CI: 1.36-5.26), age (> 65 OR: 2.24, 95%CI: 1.34-3.75), neutrophil count at registration (/1000/μl: OR: 0.8, 95%CI: 0.67-0.95), pre-/post-operation (pre-: OR: 0.51, 95%CI: 0.29-0.88), and PEG-G (OR: 0.04, 95%CI: 0.01-0.34). There were no significant differences in the frequency of grade 3 adverse events, hospitalization, intake of oral antibiotics, and relative dose intensity between the visiting group and the non-visiting group. Therapeutic daily G-CSF was more frequently used in the visiting group than in the non-visiting group. Conclusions: FN occurred at a rate higher than 20% in these 3 regimens, most frequently in TC. Neutrophil count at registration was found to be one of the risk factors of FN. The current practice of prescribing antibiotics without hematologic tests is acceptable for FN management because the outcomes were not significantly different between the visiting group and the non-visiting group. Citation Format: Takashi Ishikawa, Kentaro Sakamaki, Kazutaka Narui, Hideki Nishimura, Takafumi Sangai, Kentaro Tamaki, Yoshie Hasegawa, Ken-ichi Watanabe, Nobuyasu Suganuma, Shintaro Michishita, Sadatoshi Sugae, Tomohiko Aiharya, Koichiro Tsugawa, Hiroshi Kaise, Hirofumi Mukai. Prospective cohort study of febrile neutropenia in breast cancer patients with neoadjuvant and adjuvant chemotherapy: CSPOR-BC FN Study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-09.

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.

PCN111 - Cost-Effectiveness and Cost-Utility of Granulocyte Colony-Stimulating Factors in the Primary Prophylaxis of Chemotherapy Induced Febrile Neutropenia (FN) in Breast Cancer Patients in Greece: A Comparative Analysis

To conduct an economic evaluation comparing pegfilgrastim with filgrastim or lenograstim used either in an 11-day regimen or in a 6-day regimen for the prophylaxis of febrile neutropenia (FN) in breast cancer patients, in the Greek health care setting. A cost-effectiveness model was locally adapted from the public third-party-payer perspective. Efficacy and utility values extracted from published studies were considered in the model. The analysis was conducted for a 6-cycle horizon, to reflect the common clinical practice in Greece. Drug acquisition costs, administration costs and FN management reimbursed costs were considered (in €2014). The outcomes of the model were the incremental cost per additional FN event avoided and per QALY gained (ICER) of pegfilgrastim to its comparators. The ICERs were evaluated at the predetermined willingness-to-pay threshold of €34,000/QALY gained. The incremental cost per additional FN event avoided with pegfilgrastim ranged between €11,015 and €27,079 compared to 11-day regimens of originator and a biosimilar filgrastim respectively, while pegfilgrastim was found to be dominant compared to the 11-day regimen of lenograstim. Comparing pegfilgrastim with the 6-day regimen of filgrastim and lenograstim, it was found that the ICER per additional FN event avoided ranged between €9,538 and €15,207 in case of lenograstim and biosimilar filgrastim respectively. Similarly, cost-utility analysis revealed that pegfilgrastim was cost-effective over 11-day and 6-day regimens of originator filgrastim with ICERs of €11,065 and €19,942/QALY gained, respectively. Compared to lenograstim, pegfilgrastim was found to be dominant over the 11-day regimen and cost-effective over the 6-day regimen (ICER: €15,546). Our findings suggests that pegfilgrastim for the prophylaxis of chemotherapy-induced FN in breast cancer patients is associated with greater health benefit and lower cost over 11-day use of lenograstim, while it is a cost-effective option over either the 6-day or the 11-day regimen of biosimilar filgrastim, in Greece.

Chronic comorbid conditions associated with risk of febrile neutropenia in breast cancer patients treated with chemotherapy

Chemotherapy-induced febrile neutropenia (FN) is associated with increased patient mortality and health care costs. Comorbid conditions such as liver and renal dysfunction have been linked to increased risk of FN. However, the effects of other chronic comorbid conditions on risk of FN have not been well studied. To examine the association between chronic comorbid conditions and FN in breast cancer patients, we identified incident breast cancer patients from 2000 to 2009 treated with chemotherapy at Kaiser Permanente Southern California, a large managed care organization. Patients who received primary prophylactic granulocyte colony-stimulating factor (G-CSF) were excluded. We assessed history of comorbid conditions prior to cancer diagnosis using ICD-9 codes and disease registries. FN events were identified in the first chemotherapy cycle using a combination of ICD-9 codes and hospital discharge diagnoses. For each comorbid condition, propensity scores that included patient characteristics and other predisposing comorbid conditions were calculated and adjusted for in Cox models to determine associations between that comorbid condition and FN. We also evaluated secondary models that additionally adjusted for cancer stage, baseline absolute neutrophil count (ANC), chemotherapy regimen, and dose reductions. A total of 7,127 breast cancer patients were included; median age was 55years, and the majority had localized (47%) or regional (49%) disease at diagnosis. In the first chemotherapy cycle, 335 (4.7%) patients developed FN. Congestive heart failure (HR=3.0; 95% CI: 1.3-5.9), osteoarthritis (HR=2.0; 95% CI: 1.4-2.8), previous cancer (HR=3.4; 95% CI: 1.2-7.5), and thyroid disorder (HR=1.6; 95% CI: 1.1-2.3) were associated with increased risk of FN. These estimates were similar to those from secondary models that also adjusted for additional cancer and treatment-related covariates. Our findings suggest that several chronic comorbid conditions may be associated with risk of FN. This information, if confirmed by others, may aid clinical decision making with respect to use of prophylactic G-CSF during chemotherapy treatment.

P5-18-05: Incidence of Febrile Neutropenia in Patients Treated with Docetaxel and Cyclophosphamide (TC) for Adjuvant Breast Cancer.

Abstract Background: Adjuvant docetaxel with cyclophosphamide (TC) chemotherapy use in the community is common based on its improved disease outcomes compared to doxorubicin with cyclophosphamide (AC) treatment, lack of cardiac toxicity associated with anthracyclines, and perceived low incidence of febrile neutropenia (FN). In the pivotal trial of AC versus TC, the incidence of FN in breast cancer patients who received TC treatment was 4% in patients under 65 years and 8% in patients greater than 65 years. Growth factors (CSF) were not used in the trial, but antibiotics were used significantly. FN rates of 11.6% to 50% have been reported in multiple small studies, prompting warnings that primary prophylaxis with growth factor should be used. The true incidence of FN in community based patients may be higher than in the original clinical trial population as non-trial patients may have risk factors known to increase the risk for chemotherapy-induced FN, including increased age or other comorbid conditions. We wanted to know the incidence of FN in patients receiving TC chemotherapy who were not given primary prophylaxis with CSF. Methods: Using our electronic medical record system, a retrospective review of patients starting TC for breast cancer in 2010 at Kaiser Permanente Northern California was included. Patients had started a four or six cycle regimen of docetaxel 75 mg/m2 and cyclophosphamide 600 mg/m2 every 21 days. Patients were stratified into two groups: (1) CSF primary prophylaxis given with the first cycle versus (2) no CSF primary prophylaxis given with the first cycle. CSF prophylaxis was given by physician choice. FN episodes were defined with a clinical diagnosis code for FN from emergency department visits or hospitalizations. The primary outcome was the incidence of TC-induced FN in patients who did not receive CSF primary prophylaxis with the first cycle of treatment. Results: 332 patients with a mean age of 57.9 years (range 30.5 to 83.6 years) were included. Of these, 204 (61.4%) did not receive primary CSF prophylaxis (mean age 57.4 years, range 30.5 to 83.6 years), and 128 (38.6%) received primary CSF prophylaxis (mean age 58.5 years, range 36.6 to 82.4 years). The incidence of FN during any cycle was 24.5% (50/204) in those who did not receive primary CSF prophylaxis and 8.6% (11/128) in those who did (p=0.0003). Patients were hospitalized for FN for a total of 174 days (mean 3.2 days, range 1 to 13 days). Mean days hospitalized were 3.2 in each group. We will present risk factors associated with the development of FN. Conclusion: In the largest population based report to date, we report the incidence of febrile neutropenia to be 24.5% in patients not receiving primary CSF prophylaxis. The rate is higher than originally reported for TC. Primary prophylaxis with CSF should be considered when treating this patient population with TC chemotherapy. Further analysis, including risk factor assessment, will be presented. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-18-05.

Impact of colony-stimulating factors to reduce febrile neutropenic events in breast cancer patients receiving docetaxel plus cyclophosphamide chemotherapy

Data from US Oncology Adjuvant Trial 9735 has shown that four cycles of docetaxel plus cyclophosphamide (TC) improved disease-free and overall survival when compared against doxorubicin and cyclophosphamide (AC) in early-stage breast cancer. The febrile neutropenia (FN) rate was 4% in this study without primary granulocyte colony-stimulating factors (G-CSF) prophylaxis. However, the incidence of docetaxel-induced myelosuppression is recognized to be higher among Asian population. Hence, this study was designed to evaluate the impact of G-CSF to reduce FN-related events in Asian cancer patients treated with TC. This retrospective cohort study was conducted on Asian breast cancer patients who have received intravenous docetaxel 75 mg/m(2) and cyclophosphamide 600 mg/m(2) between 2006 to 2008. Patients did not receive oral antibiotic prophylaxis, and prophylactic G-CSF after chemotherapy was prescribed under the discretion of the primary oncologist. During cycle 1 of chemotherapy, 6.3% patients received G-CSF manifested FN, while 25% patients who did not receive G-CSF manifested FN (RR = 0.252, 95% CI 0.102 to 0.622). Introduction of G-CSF as primary prophylaxis provided an absolute risk reduction of FN events by 18.7%. Chemotherapy doses were maintained throughout all cycles. Patients with pretreatment white blood cell counts (WBC) below 6.0 × 10(3)/mm(3) and absolute neutrophil counts (ANC) below 3.1 × 10(3)/mm(3) were associated with higher rates of FN during Cycle 1 (p = 0.009, p = 0.007). Our findings indicate that TC was associated with higher rates of FN than reported in the clinical trial. The 25% incidence fulfills the requirement of primary prophylaxis with G-CSF. Routine administration of G-CSF is highly recommended to reduce the rates of FN in breast cancer patients receiving TC.

Once-per-cycle pegfilgrastim in breast cancer patients treated with docetaxel/epidoxorubicin/cyclophosphamide

The incidence of neutropenia following combination chemotherapy is significant in breast cancer and impairs patients' quality of life. Colony-stimulating factors significantly decrease the risk of febrile neutropenia (FN). Aim of the present study was to assess the efficacy and safety profile of once-per-cycle pegfilgrastim in reducing FN in breast cancer patients treated with docetaxel (75 mg/m(2)), epidoxorubicin (75 mg/m(2)), cyclophosphamide (500 mg/m(2)) administered every 3 weeks. Thirty-five breast cancer patients were enrolled. Chemotherapy was administered in adjuvant, neoadjuvant and metastatic setting respectively in 26, 4 and 5 patients. Toxicity was monitored with programmed clinical evaluation and blood sampling. All patients completed the therapeutic programme consisting of six cycles for overall 210 cycles. The FN appeared in 6 out of 35 patients (17%), requiring dose reduction in 3 patients. Hypertransaminasemia was registered in two patients. In one patient pegfilgrastim administration was stopped because of skin hypersensitivity reaction. In conclusion, pegfilgrastim was able to maintain doses and timing of docetaxel/epidoxorubicin/cyclophosphamide in almost all breast cancer patients treated in this series. The reduced need for daily administration of colony-stimulating factors, blood sampling, antibiotic therapy and hospitalization has a significant impact in terms of both quality of life and pharmaco-economic evaluations.