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.

Febrile Neutropenia Rates with Adjuvant Docetaxel and Cyclophosphamide Chemotherapy in Early Breast Cancer: Discrepancy between Published Reports and Community Practice—An Opdated Analysis

“…More recently, in the first cycle only, the fn incidence in that trial was reported to be 2.8% with primary prophylaxis, which increased to 9.5% without it 10 . Our data are consistent with those from another report 11 that showed a significant difference in the rate of fn with (8.6%) or without (24.5%) primary prophylaxis during adjuvant tc chemotherapy. Finally, a recent meta-analysis 12 looking at 902 patients treated with tc chemotherapy estimated the fn rate to be 29% without primary prophylaxis.…”

Neutropenic fever rates with adjuvant docetaxel and cyclophosphamide in early breast cancer: audit from regional cancer centre in New South Wales

“…TC is a common adjuvant chemotherapy protocol used for management of early breast cancer. The reported incidence of neutropenic fever in the largest randomised trial for this regimen is 5% and 9.5% in the first cycle without primary GCSF prophylaxis . One of the largest series of this protocol from Canada with 134 patients reported 38% incidence of neutropenic fever without primary prophylaxis similar to our study .…”

“…The updated result of this study reported a neutropenic fever rate of 5% . Many recent studies from the real‐world practice have shown a very high neutropenia rate with this protocol . A recent meta‐analysis confirmed that the risk of neutropenic fever is >20% with this regimen and upfront prophylaxis with colony‐stimulating factors may be recommended with this protocol .…”

Dose modifications in adjuvant chemotherapy for solid organ malignancies: A systematic review of clinical trials

“…In a review, Weycker et al 6 reported rates of febrile neutropenia between 8.8% and 10.6%, albeit in settings where more than 50% of patients received G-CSF as primary prophylaxis. Many other series 7,8 Febrile neutropenia rates were higher (11.5%) than what was seen in TROPIC trial (8%) despite use of G-CSF as primary prophylaxis in 47% of patients. 10 However, a subsequent trial comparing 20 with 25 mg/m 2 showed non-inferiority with less toxicity.…”